Collection of Toxicology Reports

The collection is a repository of open access articles dedicated to all aspects of toxicology research and clinical sciences. The collection may include articles related to the following subjects: adverse effects of xenobiotics on the health of humans and animals, influence of diseases in humans or model animals on chemically induced toxicity, toxicity of natural products and traditional medicines, clinical case reports involving exposure to toxins, environmental and occupational exposure to toxins, other areas of toxicological research.

DOCUMENTS63
VIEWS1289
SCORE5

SCORE PERCENTILE100

Diosmetin protects against retinal injury via reduction of DNA damage and oxidative stress
Z. Shen, J. Shao, J. Dai, Y. Lin, X. Yang, J. Ma, Q. He, B. Yang, K. Yao, P. Luo

Toxicology Reports (2016). Vol. 3

Abstract
Visual impairment is a global public health problem that needs new candidate drugs. Chrysanthemum is a traditional Chinese drug, famous for its eye-protective function, with an unclear mechanism of action. To determine how chrysanthemum contributes to vision, we identified, for the first time, the component of chrysanthemum, diosmetin (DIO), which acts in protecting the injured retina in an adriamycin (ADR) improving model. We observed that DIO could attenuate the apoptosis of retinal cells in Sprague–Dawley rats and verified this effect in cultured human retinal pigment epithelium (RPE) cells, ARPE-19. Our further study on the mechanism revealed the counteractive effect of DIO on the attenuation of DNA damage and oxidative stress, which occurs in a wide range of retinal disorders. These results collectively promise the potential value of DIO as a retinal-protective agent for disorders that lead to blindness. In addition, we identified, for the first time, the component of chrysanthemum, DIO, which acts in protecting the injured retina.
Abstract
Visual impairment is a global public health problem that needs new candidate drugs. Chrysanthemum is a traditional Chinese drug, famous for its eye-protective function, with [...]
- 18
- read
Oral administration of Nigella sativa oil ameliorates the effect of cisplatin on membrane enzymes, carbohydrate metabolism and oxidative damage in rat liver
Z. Farooqui, M. Afsar, S. Rizwan, A. Khan, F. Khan

Toxicology Reports (2016). Vol. 3

Abstract
Cisplatin (CP) is a potent anti-cancer drug widely used against solid tumors. However, it exhibits pronounced adverse effects including hepatotoxicity. Several strategies were attempted to prevent CP hepatotoxicity but were not found suitable for therapeutic application. Nigella sativa has been shown to prevent/reduce the progression of certain type of cardiovascular, kidney and liver diseases. Present study investigates whether N. sativa oil (NSO) can prevent CP induced hepatotoxic effects. Rats were divided into four groups viz. control, CP, NSO and CPNSO. Animals in CPNSO and NSO group were administered NSO (2 ml/kg bwt, orally) with or without single hepatotoxic dose of CP (6 mg/kg bwt, i.p.) respectively. CP hepatotoxicity was recorded by increased serum ALT and AST activities. CP treatment caused oxidant/antioxidant imbalances as reflected by increased lipid peroxidation and decreased enzymatic and non-enzymatic antioxidants. Furthermore, the activities of various carbohydrate metabolism and membrane enzymes were altered by CP treatment. In contrast, NSO administration to CP treated rats, markedly ameliorated the CP elicited deleterious alterations in liver. Histopathological observations showed extensive liver damage in CP treated animals while greatly reduced tissue injury in CPNSO group. In conclusion, NSO appears to protect CP induced hepatotoxicity by improving energy metabolism and strengthening antioxidant defense mechanism.
Abstract
Cisplatin (CP) is a potent anti-cancer drug widely used against solid tumors. However, it exhibits pronounced adverse effects including hepatotoxicity. Several strategies [...]
- 13
- read
Fish oil prevents excessive accumulation of subcutaneous fat caused by an adverse effect of pioglitazone treatment and positively changes adipocytes in KK mice
Y. Iizuka, H. Kim, M. Nakasatomi, T. Izawa, S. Hirako, A. Matsumoto

Toxicology Reports (2016). Vol. 3

Abstract
Pioglitazone, a thiazolidinedione (TZD), is widely used as an insulin sensitizer in the treatment of type 2 diabetes. However, body weight gain is frequently observed in TZD-treated patients. Fish oil improves lipid metabolism dysfunction and obesity. In this study, we demonstrated suppression of body weight gain in response to pioglitazone administration by combination therapy of pioglitazone and fish oil in type 2 diabetic KK mice. Male KK mice were fed experimental diets for 8 weeks. In safflower oil (SO), safflower oil/low-dose pioglitazone (S/PL), and safflower oil/high-dose pioglitazone (S/PH) diets, 20% of calories were provided by safflower oil containing 0%, 0.006%, or 0.012% (wt/wt) pioglitazone, respectively. In fish oil (FO), fish oil/low-dose pioglitazone (F/PL), and fish oil/high-dose pioglitazone (F/PH) diets, 20% of calories were provided by a mixture of fish oil and safflower oil. Increased body weight and subcutaneous fat mass were observed in the S/PL and S/PH groups, however, diets containing fish oil were found to ameliorate these changes. Hepatic mRNA levels of lipogenic enzymes were significantly decreased in fish oil-fed groups. These findings demonstrate that the combination of pioglitazone and fish oil decreases subcutaneous fat accumulation, ameliorating pioglitazone-induced body weight gain, through fish oil-mediated inhibition of hepatic de novo lipogenesis.
Abstract
Pioglitazone, a thiazolidinedione (TZD), is widely used as an insulin sensitizer in the treatment of type 2 diabetes. However, body weight gain is frequently observed in TZD-treated [...]
- 19
- read
ABC gene-ranking for prediction of drug-induced cholestasis in rats
Y. Cherkas, M. McMillian, D. Amaratunga, N. Raghavan, J. Sasaki

Toxicology Reports (2016). Vol. 3

Abstract
As legacy toxicogenomics databases have become available, improved data mining approaches are now key to extracting and visualizing subtle relationships between toxicants and gene expression. In the present study, a novel “aggregating bundles of clusters” (ABC) procedure was applied to separate cholestatic from non-cholestatic drugs and model toxicants in the Johnson & Johnson (Janssen) rat liver toxicogenomics database [3] . Drug-induced cholestasis is an important issue, particularly when a new compound enters the market with this liability, with standard preclinical models often mispredicting this toxicity. Three well-characterized cholestasis-responsive genes (Cyp7a1, Mrp3 and Bsep) were chosen from a previous in-house Janssen gene expression signature, these three genes show differing, non-redundant responses across the 90+ paradigm compounds in our database. Using the ABC procedure, extraneous contributions were minimized in comparisons of compound gene responses. All genes were assigned weights proportional to their correlations with Cyp7a1, Mrp3 and Bsep, and a resampling technique was used to derive a stable measure of compound similarity. The compounds that were known to be associated with rat cholestasis generally had small values of this measure relative to each other but also had large values of this measure relative to non-cholestatic compounds. Visualization of the data with the ABC-derived signature showed a very tight, essentially identically behaving cluster of robust human cholestatic drugs and experimental cholestatic toxicants (ethinyl estradiol, LPS, ANIT and methylene dianiline, disulfiram, naltrexone, methapyrilene, phenacetin, alpha-methyl dopa, flutamide, the NSAIDs–—indomethacin, flurbiprofen, diclofenac, flufenamic acid, sulindac, and nimesulide, butylated hydroxytoluene, piperonyl butoxide, and bromobenzene), some slightly less active compounds (3′-acetamidofluorene, amsacrine, hydralazine, tannic acid), some drugs that behaved very differently, and were distinct from both non-cholestatic and cholestatic drugs (ketoconazole, dipyridamole, cyproheptadine and aniline), and many postulated human cholestatic drugs that in rat showed no evidence of cholestasis (chlorpromazine, erythromycin, niacin, captopril, dapsone, rifampicin, glibenclamide, simvastatin, furosemide, tamoxifen, and sulfamethoxazole). Most of these latter drugs were noted previously by other groups as showing cholestasis only in humans. The results of this work suggest that the ABC procedure and similar statistical approaches can be instrumental in combining data to compare toxicants across toxicogenomics databases, extract similarities among responses and reduce unexplained data varation.
Abstract
As legacy toxicogenomics databases have become available, improved data mining approaches are now key to extracting and visualizing subtle relationships between toxicants [...]
- 6
- read
Sulfur mustard-stimulated proteases and their inhibitors in a cultured normal human epidermal keratinocytes model: A potential approach for anti-vesicant drug development
X. Jin, R. Ray, P. Ray

Toxicology Reports (2016). Vol. 3

Abstract
Protease stimulation in cultured normal human epidermal keratinocytes (NHEK) due to sulfur mustard (SM) exposure is well documented. However, the specific protease(s) stimulated by SM and the protease substrates remain to be determined. In this study, we observed that SM stimulates several proteases and the epidermal-dermal attachment protein laminin-5 is one of the substrates. We propose that following SM exposure of the skin, laminin-5 degradation causes the detachment of the epidermis from the dermis and, therefore, vesication. We utilized gelatin zymography, Western blotting, immuno-fluorescence staining, and real-time polymerase chain reaction (RT-PCR) analyses to study the SM-stimulated proteases and laminin-5 degradation in NHEK. Two major protease bands (64 kDa and 72 kDa) were observed by zymography in SM-exposed cells. Addition of serine protease inhibitor (aprotinin, 100 μM), or the metalloprotease inhibitor (amastatin, 100 μM) to NHEK cultures prior to SM exposure decreased the SM-stimulated protease bands seen by zymography. These inhibitors completely or partially prevented SM-induced laminin-5 γ2 degradation as seen by Western blotting as well as immuno-fluorescence staining. Our results from Western blotting and RT-PCR studies also indicated that the membrane-type matrix metalloproteinase-1 (MT-MM-1) may be involved in SM-induced skin blistering. To summarize, our results in the NHEK model indicate the following: (a) SM stimulates multiple proteases including serine protease(s), and metalloproteases, (b) SM decreases the level of laminin-5 γ2, which is prevented by either a serine protease inhibitor or a metalloprotease inhibitor and (c) MT-MMP-1 maybe one of the proteases that is involved in skin blistering due to SM exposure.
Abstract
Protease stimulation in cultured normal human epidermal keratinocytes (NHEK) due to sulfur mustard (SM) exposure is well documented. However, the specific protease(s) stimulated [...]
- 12
- read
Inhibitory effect of Camellia sinensis , Ilex paraguariensis and Ardisia compressa tea extracts on the proliferation of human head and neck squamous carcinoma cells
M. Ramirez-Mares, H. Kobayashi, E. Mejia

Toxicology Reports (2016). Vol. 3

Abstract
In vitro cell proliferation, cell cycle arrest and induction of apoptosis were investigated, using three human head and neck squamous cell carcinoma (HNSCC) cell lines (OSCC-3, SCC-61, and SQ-20B). Aqueous extracts of Camellia sinensis, Ilex paraguariensis, and Ardisia compressa were tested and (−) epigallocatechin-3-gallate (EGCG) was used for comparison. For EGCG the IC50 values were between 80 and 166 μM and for the extracts among 75 and 505 μM eq. (+) catechin, with C. sinensis demonstrating dominant cytotoxicity. There was not a correlation between antioxidant capacity and cytotoxicity. Flow cytometry analysis revealed similarities in response for EGCG and C. sinensis . The A. compressa extract altered DNA distribution (P < 0.05) and was the most effective in induction of apoptosis via caspases (P < 0.05). Not all HNSCC cells tested responded to the same preventive agents. The fact that A. compressa inhibits HNSCC cell proliferation makes this aqueous extract a potential source of chemopreventive agents.
Abstract
In vitro cell proliferation, cell cycle arrest and induction of apoptosis were investigated, using three human head and neck squamous cell carcinoma (HNSCC) cell lines (OSCC-3, [...]
- 7
- read
Brain regions and monoaminergic neurotransmitters that are involved in mouse ambulatory activity promoted by bupropion
T. Umezu, Y. Shibata

Toxicology Reports (2016). Vol. 3

Abstract
Bupropion (BUP), a substituted phenyl-ethylamine, has been utilized for the treatment of depression and for smoking cessation, however, one concern is that BUP may increase a risk of psychosis similar to other substituted phenyl-ethylamine amphetamine (AMPH) and methamphetamine (MetAMPH). BUP promotes ambulation in mice and causes behavioral sensitization on the ambulation-promoting effect when repeatedly administered as well as AMPH and MetAMPH. The present study aimed to elucidate brain regions and monoaminergic neurotransmitters that are involved in the ambulation-promoting effect of BUP. c-Fos-like immunoreactivity (c-Fos-IR) mapping in brain in combination with measuring ambulatory activity was conducted to determine brain region(s) that is involved in the ambulatory effect of BUP. Three kinds of statistical analyses for c-Fos-IR in 24 brain regions consistently showed that c-Fos-IR in the Caudate putamen (CPu) is positively correlated with the ambulatory response to BUP. In addition, multiple regression analysis indicated that the ambulatory response is a function of c-Fos-IR not only in the CPu but also in the lateral septum nucleus (LS), median raphe nucleus (MnR), lateral globus pallidus (LGP), medial globus pallidus (MGP), locus coeruleus (LC) and ventral hypothalamic nucleus (VMH). Effects of BUP on monoaminergic neurotransmitters in the CPu were examined using in vivo microdialysis method, as the pharmacological experiments indicated that monoaminergic neurotransmitters, dopamine (DA) in particular, mediate the ambulatory response to BUP. Response of DA in the CPu to BUP was parallel to the ambulatory response, showing that DA in the CPu is involved in the ambulatory response to BUP. The present study also suggests that other brain regions such as the LC, the origin nucleus of norepinephrine (NE) neurons, and another neurotransmitter NE may also play some roles for the ambulatory response to BUP, however, further studies are needed to elucidate the roles.
Abstract
Bupropion (BUP), a substituted phenyl-ethylamine, has been utilized for the treatment of depression and for smoking cessation, however, one concern is that BUP may increase [...]
- 15
- read
Anti-cancer activity of ZnO chips by sustained zinc ion release
S. Moon, W. Choi, S. Choi, E. Kim, J. Kim, J. Lee, S. Kim

Toxicology Reports (2016). Vol. 3

Abstract
We report anti-cancer activity of ZnO thin-film-coated chips by sustained release of zinc ions. ZnO chips were fabricated by precisely tuning ZnO thickness using atomic layer deposition, and their potential to release zinc ions relative to the number of deposition cycles was evaluated. ZnO chips exhibited selective cytotoxicity in human B lymphocyte Raji cells while having no effect on human peripheral blood mononuclear cells. Of importance, the half-maximal inhibitory concentration of the ZnO chip on the viability of Raji cells was 121.5 cycles, which was comparable to 65.7 nM of daunorubicin, an anti-cancer drug for leukemia. Molecular analysis of cells treated with ZnO chips revealed that zinc ions released from the chips increased cellular levels of reactive oxygen species, including hydrogen peroxide, which led to the down-regulation of anti-apoptotic molecules (such as HIF-1α, survivin, cIAP-2, claspin, p-53, and XIAP) and caspase-dependent apoptosis. Because the anti-cancer activity of ZnO chips and the mode of action were comparable to those of daunorubicin, the development and optimization of ZnO chips that gradually release zinc ions might have clinical anti-cancer potential. A further understanding of the biological action of ZnO-related products is crucial for designing safe biomaterials with applications in disease treatment.
Abstract
We report anti-cancer activity of ZnO thin-film-coated chips by sustained release of zinc ions. ZnO chips were fabricated by precisely tuning ZnO thickness using atomic layer [...]
- 37
- read
Hepatoprotective effect of grape seed proanthocyanidins on Cadmium-induced hepatic injury in rats: Possible involvement of mitochondrial dysfunction, inflammation and apoptosis
S. Miltonprabu, . Nazimabashir, V. Manoharan

Toxicology Reports (2016). Vol. 3

Abstract
The present study was undertaken to evaluate the possible ameliorative role of grape seed proanthocyanidins (GSP) against Cadmium (Cd) induced hepatic inflammation, apoptosis and hepatic mitochondrial toxicity in rats. Male Wistar rats were distributed in four experimental groups: control, GSP, Cd and Cd + GSP. Exposure to a hepatotoxic dose of Cd (5 mg/kg BW) caused liver damage, coupled with enhanced reactive oxygen species (ROS) generation, increased inflammation and apoptosis in liver with increased DNA damage in hepatocytes of rats. Mitochondria were isolated from the hepatic tissues of rats from each group. Our results showed significant decrease in the tri-carboxylic acid cycle enzymes, increased mitochondrial swelling, inhibition of cytochrome c oxidase activity and complex I–III, II–III and IV mediated electron transfer, decreased mitochondrial ATPases, a reduction in calcium content and mitochondrial oxygen consumption in Cd treated rats. All these molecular changes caused by Cd were alleviated by the pre-supplementation with GSP (100 mg/kg BW). The ultra structural changes in the liver also support our findings. From our results, it is clearly indicated that the free radical scavenging, metal chelating and antioxidant potentials of GSP might be the possible reason, responsible for the rescue action against Cd induced mitochondrial damage in the liver of rats.
Abstract
The present study was undertaken to evaluate the possible ameliorative role of grape seed proanthocyanidins (GSP) against Cadmium (Cd) induced hepatic inflammation, apoptosis [...]
- 27
- read
Apocynin reduced doxycycline-induced acute liver injury in ovariectomized mice
S. Mitazaki, M. Hashimoto, Y. Matsuhashi, S. Honma, M. Suto, N. Kato, K. Hiraiwa, M. Yoshida, S. Abe

Toxicology Reports (2016). Vol. 3

Abstract
To determine the physiological role of estrogen in the development of liver injury, we examined the sensitivities of sham and ovariectomy (ovx) mice against doxycycline (DOXY)-induced acute liver injury. Ovx or sham operation was performed in C57BL/6J wild-type female mice of eight weeks of age. Sham mice and ovx mice were treated with DOXY (240 mg/kg ip) 8 weeks after the operation, 30 min after apocynin (5 mg/kg) or saline administration. Blood and liver samples were obtained at 3 and 6 h after DOXY administration. Liver dysfunction occurred soon after DOXY administration and became more severe in ovx mice than in sham mice. At early phase after DOXY injection, TNF-α and iNOS inductions upregulated almost the same levels in sham and ovx mice. On the other hand, expression levels of IL-6, IL-10, c-fos, cox-2 and HO-1, downstream genes of TNF-α, were significantly increased in ovx mice compared to those in sham mice, correlated with liver dysfunction. In addition, apocynin, a NADPH oxidase (Nox) inhibitor, totally improved DOXY-induced liver injury in both sham and ovx mice, indicating that reactive oxygen species generated through Nox activation by DOXY are responsible for development of acute liver injury.
Abstract
To determine the physiological role of estrogen in the development of liver injury, we examined the sensitivities of sham and ovariectomy (ovx) mice against doxycycline (DOXY)-induced [...]
- 13
- read
Evaluation of the anti-inflammatory activities of Quillaja saponaria Mol. saponin extract in mice
S. Sarkhel

Toxicology Reports (2016). Vol. 3

Abstract
Quillaja saponaria bark contains a high percentage of triterpene saponins and has been used for centuries as antiinflammatory and analgesic agent in Chilean folk medicine. In the Present study the anti-inflammatory activities of the aqueous extract of commercially partially purified saponin from Quillaja saponari a Mol. in in vivo animal models. Aqueous extract of the plant material was prepared by cold maceration. The anti-inflammatory activity of a commercial Quillaja saponaria Mol. (QS) saponin extract was investigated by carragenan induced mice paw edema model for acute inflammation (Winter, 1962) [16] . The anti-inflammatory activity was evaluated by carragenan in paw edema model in swiss albino mice (18–20 g). The anti-inflammatory activity was found to be dose dependent in carragenan induced paw edema. QS was found to significantly (p < 0.05) reduce the carragenan induced mice paw edema (38.59%, 20 mg/kg bw) as compared to carragenan control. The percentage inhibition of standard anti-inflammatory drug indomethacin was (55%, 10 mg/kg, bw). The results of the present study demonstrate that the aqueous extract of Quillaja saponaria saponins (QS) possess significant anti-inflammatory activity.
Abstract
Quillaja saponaria bark contains a high percentage of triterpene saponins and has been used for centuries as antiinflammatory and analgesic agent in Chilean folk medicine. [...]
- 29
- read
Assessment of heavy metals contamination and human health risk in shrimp collected from different farms and rivers at Khulna-Satkhira region, Bangladesh
T. Sarkar, M. Alam, N. Parvin, Z. Fardous, A. Chowdhury, S. Hossain, M. Haque, N. Biswas

Toxicology Reports (2016). Vol. 3

Abstract
This study is aimed to assess the heavy metals contamination and health risk in Shrimp (Macrobrachium rosenbergii and Penaeus monodon ) collected from Khulna-Satkhira region in Bangladesh. The results showed that the Pb concentrations (0.52–1.16 mg/kg) in all shrimp samples of farms were higher than the recommended limit. The Cd levels (0.05–0.13 mg/kg) in all samples and Cr levels in all farms except tissue content at Satkhira farm were higher than the permissible limits. The individual concentration of Pb, Cd, and Cr between shrimp tissue and shell in all rivers and farms were not statistically significant (P > 0.05). Target hazard quotient (THQ) and hazard index (HI) were estimated to assess the non-carcinogenic health risks. Shrimp samples from all locations under the current study were found to be safe for consumption, the possibility of health risk associated with non-carcinogenic effect is very low for continuous consumption for 30 years.
Abstract
This study is aimed to assess the heavy metals contamination and health risk in Shrimp (Macrobrachium rosenbergii and Penaeus monodon ) collected from Khulna-Satkhira region [...]
- 75
- read
Curcuminoids from Curcuma longa L. reduced intestinal mucositis induced by 5-fluorouracil in mice: Bioadhesive, proliferative, anti-inflammatory and antioxidant effects
E. Filho, P. Ávila, C. Bastos, A. Batista, L. Naves, R. Marreto, E. Lima, E. Mendonça, M. Valadares

Toxicology Reports (2016). Vol. 3

Abstract
Intestinal mucositis is a frequent limiting factor in anticancer therapy and there is currently no broadly effective treatment targeted to cure this side effect. This study aimed to evaluate the effects of a mucoadhesive formulation containing curcuminoids (MFC) from Curcuma longa L. on the pathogenesis of 5-fluorouracil (5-FU)-induced intestinal mucositis. Three intraperitoneal 5-FU injections (200 mg/kg) were used to induce intestinal mucositis in adult Swiss male mice. Treatment was provided orally (MFC 3.75, 7.5 and 15 mg/kg), thirty minutes before 5-FU injections, daily until euthanasia. Duodenal samples were collected to perform morphometric and histopathological analysis, to investigate the expression of Ki-67, p53, Bax and Bcl-2 by immunohistochemistry, to evaluate neutrophil activity myeloperoxidase (MPO)-mediated and oxidative stress by malondialdehyde (MDA) determination. Mice body weight was assessed as well. As expected, 5-FU induced a significant weight loss (∼17%, P < 0.001), shortening in villi height (∼55.4%) and crypts depth (∼47%), and increased (∼64%) the histological severity score when compared to other groups (P < 0.05). These pathological changes were markedly alleviated by the three MFC treatment doses (P < 0.05), in special with the dose MFC 15 mg/kg. This dose also stimulated cell proliferation by ∼90% in the epithelial cells lining from villi and crypts (P < 0.05), reduced MPO levels and MDA formation by 60% and 44%, respectively (P < 0.05). Our data suggest the therapeutic potential of the formulation for treating intestinal mucositis in mice. Supplementary studies are underway searching for the elucidation of mechanisms involved in the protective effects of MFC in order to make this formulation a clinical tool for mucositis treatment.
Abstract
Intestinal mucositis is a frequent limiting factor in anticancer therapy and there is currently no broadly effective treatment targeted to cure this side effect. This study [...]
- 5
- read
Effect of Hecogenin on DNA instability
M. Cruz, S. Barroso, J. Navoni, M. Teles, J. Barbosa-Filho, H. Rocha, V. Amaral

Toxicology Reports (2016). Vol. 3

Abstract
Hecogenin is a sapogenin found in Agave species in high quantities and is responsible for the many therapeutic effects of these medicinal plants. In addition, this compound is also widely used in the pharmaceutical industry as a precursor for the synthesis of steroidal hormones and anti-inflammatory drugs. Despite Hecogenin being widely used, little is known about its toxicological properties. Therefore, the present study aimed to investigate the cytotoxic, genotoxic and mutagenic effects of Hecogenin on HepG2 cells. Cytotoxicity was analyzed using the MTT test. Then, genotoxic and mutagenic potentials were assessed by comet assay and cytokinesis-block micronucleus assay, respectively. Cytotoxic effect was observed only when cells were exposed to concentrations of Hecogenin equal or higher than 100 μM. Although a lower concentration of Hecogenin caused DNA damage, a reduction on nuclear mutagenic markers in HepG2 cells was observed. The results indicated that Hecogenin treatment generated DNA damage, but in fact it would be repaired, avoiding dissemination of the damage throughout the cell division. Further studies need to be performed to confirm the observed protective effect of Hecogenin against genomic instability.
Abstract
Hecogenin is a sapogenin found in Agave species in high quantities and is responsible for the many therapeutic effects of these medicinal plants. In addition, this compound [...]
- 10
- read
Exposure of the gilthead seabream (Sparus aurata ) to sediments contaminated with heavy metals down-regulates the gene expression of stress biomarkers
S. Benhamed, F. Guardiola, S. Martínez, M. Martínez-Sánchez, C. Pérez-Sirvent, M. Mars, M. Esteban

Toxicology Reports (2016).

Abstract
Heavy metals incidence in the aquatic environment and its accumulation in fish are under constant review. Gilthead seabream (Sparus aurata ) specimens were exposed for two weeks to sediments highly concentrated in metals, collected at the Portman Bay (Murcia, Spain). The metals bioaccumulation was tested in liver, muscle and skin. The potential of the sediment exposure to induce variation of the stress biomarkers genes was conducted in liver and skin. Results revealed that sediments were highly contaminated with metals. However, following 2 weeks exposure to the sediments, Cd accumulates only in liver. Interestingly, the expression of the genes mta, hsp 70 and hsp 90 were significantly down-regulated in skin. Nevertheless, cyp1a1 gene was up-regulated only in liver. Results uphold that the stress response magnitude was organ-dependent and the skin was the most responsive tissue to metal stress conditions. These results suggest that skin should be considered as target organ for biomarkers analysis in fishes.
Abstract
Heavy metals incidence in the aquatic environment and its accumulation in fish are under constant review. Gilthead seabream (Sparus aurata ) specimens were exposed for two [...]
- 20
- read
Altered global gene expression profiles in human gastrointestinal epithelial Caco2 cells exposed to nanosilver
S. Sahu

Toxicology Reports (2016). Vol. 3

Abstract
Extensive consumer exposure to food- and cosmetics-related consumer products containing nanosilver is of public safety concern. Therefore, there is a need for suitable in vitro models and sensitive predictive rapid screening methods to assess their toxicity. Toxicogenomic profile showing subtle changes in gene expressions following nanosilver exposure is a sensitive toxicological endpoint for this purpose. We evaluated the Caco2 cells and global gene expression profiles as tools for predictive rapid toxicity screening of nanosilver. We evaluated and compared the gene expression profiles of Caco-2 cells exposed to 20 nm and 50 nm nanosilver at a concentration 2.5 μg/ml. The global gene expression analysis of Caco2 cells exposed to 20 nm nanosilver showed that a total of 93 genes were altered at 4 h exposure, out of which 90 genes were up-regulated and 3 genes were down-regulated. The 24 h exposure of 20 nm silver altered 15 genes in Caco2 cells, out of which 14 were up-regulated and one was down-regulated. The most pronounced changes in gene expression were detected at 4 h. The greater size (50 nm) nanosilver at 4 h exposure altered more genes by more different pathways than the smaller (20 nm) one. Metallothioneins and heat shock proteins were highly up-regulated as a result of exposure to both the nanosilvers. The cellular pathways affected by the nanosilver exposure is likely to lead to increased toxicity. The results of our study presented here suggest that the toxicogenomic characterization of Caco2 cells is a valuable in vitro tool for assessing toxicity of nanomaterials such as nanosilver.
Abstract
Extensive consumer exposure to food- and cosmetics-related consumer products containing nanosilver is of public safety concern. Therefore, there is a need for suitable in [...]
- 15
- read
Evaluation of biological effects of intermediate frequency magnetic field on differentiation of embryonic stem cell
S. Yoshie, Y. Ogasawara, M. Ikehata, K. Ishii, Y. Suzuki, K. Wada, K. Wake, S. Nakasono, M. Taki, C. Ohkubo

Toxicology Reports (2016). Vol. 3

Abstract
The embryotoxic effect of intermediate frequency (IF) magnetic field (MF) was evaluated using murine embryonic stem (ES) cells and fibroblast cells based on the embryonic stem cell test (EST). The cells were exposed to 21 kHz IF–MF up to magnetic flux density of 3.9 mT during the cell proliferation process (7 days) or the cell differentiation process (10 days) during which an embryonic body differentiated into myocardial cells. As a result, there was no significant difference in the cell proliferation between sham- and IF–MF-exposed cells for both ES and fibroblast cells. Similarly, the ratio of the number of ES-derived cell aggregates differentiated to myocardial cells to total number of cell aggregates was not changed by IF–MF exposure. In addition, the expressions of a cardiomyocytes-specific gene, Myl2, and an early developmental gene, Hba-x, in the exposed cell aggregate were not altered. Since the magnetic flux density adopted in this study is much higher than that generated by an inverter of the electrical railway, an induction heating (IH) cooktop, etc . in our daily lives, these results suggested that IF–MF in which the public is exposed to in general living environment would not have embryotoxic effect.
Abstract
The embryotoxic effect of intermediate frequency (IF) magnetic field (MF) was evaluated using murine embryonic stem (ES) cells and fibroblast cells based on the embryonic [...]
- 6
- read
14-day toxicity studies of tetravalent and pentavalent vanadium compounds in Harlan Sprague Dawley rats and B6C3F1/N mice via drinking water exposure
G. Roberts, M. Stout, B. Sayers, D. Fallacara, M. Hejtmancik, S. Waidyanatha, M. Hooth

Toxicology Reports (2016).

Abstract
The National Toxicology Program (NTP) performed short-term toxicity studies of tetra- and pentavalent vanadium compounds, vanadyl sulfate and sodium metavanadate, respectively. Due to widespread human exposure and a lack of chronic toxicity data, there is concern for human health following oral exposure to soluble vanadium compounds. To compare the potency and toxicological profile of vanadyl sulfate and sodium metavanadate using a short-term in vivo toxicity assay. Adult male and female Harlan Sprague Dawley (HSD) rats and B6C3F1/N mice, 5 per group, were exposed to vanadyl sulfate or sodium metavanadate, via drinking water, at concentrations of 0, 125, 250, 500, 1000 or 2000 mg/L for 14 days. Water consumption, body weights and clinical observations were recorded throughout the study, organ weights were collected at study termination. Lower water consumption, up to −80% at 2000 mg/L, was observed at most exposure concentrations for animals exposed to either vanadyl sulfate or sodium metavanadate and was accompanied by decreased body weights at the highest concentrations for both compounds. Animals in the 1000 and 2000 mg/L sodium metavanadate groups were removed early due to overt toxicity. Thinness was observed in high-dose animals exposed to either compound, while lethargy and abnormal gait were only observed in vanadate-exposed animals. Based on clinical observations and overt toxicity, sodium metavanadate appears to be more toxic than vanadyl sulfate. Differential toxicity cannot be explained by differences in total vanadium intake, based on water consumption, and may be due to differences in disposition or mechanism of toxicity.
Abstract
The National Toxicology Program (NTP) performed short-term toxicity studies of tetra- and pentavalent vanadium compounds, vanadyl sulfate and sodium metavanadate, respectively. [...]
- 16
- read
Evaluation of toxicity of biorational insecticides against larvae of the alfalfa weevil
G. Reddy, F. Antwi, G. Shrestha, T. Kuriwada

Toxicology Reports (2016). Vol. 3

Abstract
The alfalfa weevil, Hypera postica (Coleoptera: Curculionidae), is a major pest of alfalfa Medicago sativa L. (Fabaceae). While H. postica usually causes the most damage before the first cutting, in summer of 2015 damaging levels of the pest persisted in Montana well after the first harvest of alfalfa. Although conventional insecticides can control H. postica, these chemicals have adverse effects on non-target organisms including pollinators and natural enemy insects. In this context, use of biorational insecticides would be the best alternative options, as they are known to pose less risk to non-target organisms. We therefore examined the six commercially available biorational insecticides against H. postica under laboratory condition: Mycotrol® ESO (Beauveria bassiana GHA), Aza-Direct® (Azadirachtin), Met52® EC (Metarhizium brunneum F52), Xpectro OD® (B. bassiana GHA + pyrethrins), Xpulse OD® (B. bassiana GHA + Azadirachtin) and Entrust WP® (spinosad 80%). Concentrations of 0.1, 0.5, 1.0, and 2.0 times the lowest labelled rates were tested for all products. However, in the case of Entrust WP, additional concentrations of 0.001 and 0.01 times the lowest label rate were also assessed. Mortality rates were determined at 1–9 days post treatment. Based on lethal concentrations and relative potencies, this study clearly showed that Entrust was the most effective, causing 100% mortality within 3 days after treatment among all the tested materials. With regard to other biorational, Xpectro was the second most effective insecticide followed by Xpulse, Aza-Direct, Met52, and Mycotrol. Our results strongly suggested that these biorational insecticides could potentially be applied for H. postica control.
Abstract
The alfalfa weevil, Hypera postica (Coleoptera: Curculionidae), is a major pest of alfalfa Medicago sativa L. (Fabaceae). While H. postica usually causes the most damage before [...]
- 30
- read
Antioxidant protection of gallic acid against toxicity induced by Pb in blood, liver and kidney of rats
P. Reckziegel, V. Dias, D. Benvegnú, N. Boufleur, R. Barcelos, H. Segat, C. Pase, C. Santos, É. Flores, M. Bürger

Toxicology Reports (2016). Vol. 3

Abstract
The effect of the antioxidant gallic acid (GA) on Pb toxicity in blood, liver and kidney was investigated in the present study. Rats Wistar received Pb nitrate (50 mg/Kg/day, i.p., 5 days) followed by GA (13.5 mg/Kg, p.o., 3 days) or a chelating agent (EDTA, 55 mg/Kg, i.p.). As result, Pb decreased body weight, hematocrit and blood δ-aminolevulinic acid dehydratase (ALA-D) activity. In addition, high Pb levels were observed in blood and tissues, together with increased (1) lipid peroxidation in erythrocytes, plasma and tissues, (2) protein oxidation in tissues and (3) plasma aspartate transaminase (AST) levels. These changes were accompanied by decreasing in antioxidant defenses, like superoxide dismutase (SOD) activity in tissues and catalase (CAT) activity and reduced glutathione (GSH) in liver. GA was able to reverse Pb-induced decrease in body weight and ALA-D activity, as well as Pb-induced oxidative damages and most antioxidant alterations, however it did not decrease Pb bioaccumulation herein as EDTA did. Furthermore, EDTA did not show antioxidant protection in Pb-treated animals as GA did. In conclusion, GA decreased Pb-induced oxidative damages not by decreasing Pb bioaccumulation, but by improving antioxidant defenses, thus GA may be promising in the treatment of Pb intoxications.
Abstract
The effect of the antioxidant gallic acid (GA) on Pb toxicity in blood, liver and kidney was investigated in the present study. Rats Wistar received Pb nitrate (50 mg/Kg/day, [...]
- 25
- read

show more

information

About this publication

How to submit

Open access

Contact

Diosmetin protects against retinal injury via reduction of DNA damage and oxidative stress

Oral administration of Nigella sativa oil ameliorates the effect of cisplatin on membrane enzymes, carbohydrate metabolism and oxidative damage in rat liver

Fish oil prevents excessive accumulation of subcutaneous fat caused by an adverse effect of pioglitazone treatment and positively changes adipocytes in KK mice

ABC gene-ranking for prediction of drug-induced cholestasis in rats

Sulfur mustard-stimulated proteases and their inhibitors in a cultured normal human epidermal keratinocytes model: A potential approach for anti-vesicant drug development

Inhibitory effect of Camellia sinensis , Ilex paraguariensis and Ardisia compressa tea extracts on the proliferation of human head and neck squamous carcinoma cells

Brain regions and monoaminergic neurotransmitters that are involved in mouse ambulatory activity promoted by bupropion

Anti-cancer activity of ZnO chips by sustained zinc ion release

Hepatoprotective effect of grape seed proanthocyanidins on Cadmium-induced hepatic injury in rats: Possible involvement of mitochondrial dysfunction, inflammation and apoptosis

Apocynin reduced doxycycline-induced acute liver injury in ovariectomized mice

Evaluation of the anti-inflammatory activities of Quillaja saponaria Mol. saponin extract in mice

Assessment of heavy metals contamination and human health risk in shrimp collected from different farms and rivers at Khulna-Satkhira region, Bangladesh

Curcuminoids from Curcuma longa L. reduced intestinal mucositis induced by 5-fluorouracil in mice: Bioadhesive, proliferative, anti-inflammatory and antioxidant effects

Effect of Hecogenin on DNA instability

Exposure of the gilthead seabream (Sparus aurata ) to sediments contaminated with heavy metals down-regulates the gene expression of stress biomarkers

Altered global gene expression profiles in human gastrointestinal epithelial Caco2 cells exposed to nanosilver

Evaluation of biological effects of intermediate frequency magnetic field on differentiation of embryonic stem cell

14-day toxicity studies of tetravalent and pentavalent vanadium compounds in Harlan Sprague Dawley rats and B6C3F1/N mice via drinking water exposure

Evaluation of toxicity of biorational insecticides against larvae of the alfalfa weevil

Antioxidant protection of gallic acid against toxicity induced by Pb in blood, liver and kidney of rats

information

Sign up at Scipedia and complete your profile

Click on "CREATE A DOCUMENT" in your profile page

Upload your manuscript in LaTeX or Word, or create it from scratch with our online editor

Click on "SUBMIT FOR PUBLICATION" at the manuscript page, and select your preferred journal or collection

Click on "SUBMIT FOR PUBLICATION" at the manuscript page, select your preferred collection and complete the submission form

The editorial board will ensure that the publishing requirements are adhered to, before your paper is published

Categories