Experimental Hepatotoxicity Research Articles

Omega-3 fatty acids moderate oxidative and proinflammatory events in experimental hepatotoxicity in Wistar rats: comparison with livolin

Dietary supplementation with omega-3 fatty acids have been advocated because of the global preference for the omega-6 fatty acids - rich Western style diet. The study investigated the effects of omega-3 fatty acids (combination of N-3: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA); EPA/DHA ratio = 3/2) compared to livolin (Phosphatidylcholin + vitamins) on biochemical and haematological parameters in diclofenac (DF) - induced hepatotoxicity in male Wistar rats. Twenty five rats were used. They were divided into 5 groups (n = 5) which included: Group 1-Control (untreated); Group 2-DF control; Group 3-DF + Low N-3; Group 4-DF+High N-3; and, Group 5-DF + Livolin. Group 2 received DF at 10 mg/kg b.w. (i.m.) during the first 7days of the experiment, thereafter; they were administered distilled water (0.1 ml) for three weeks. Groups 3, 4, and 5 were pre-treated with DF during the first 7days of the experiment, afterwards, they were post-treated with N-3 and livolin at 100, 300, and 5.2 mg/kg b.w. (p.o.) respectively for 21days.The results showed that DF caused significant increases in MDA, LDH, proinflammatory markers, ALT, AST, and ALP activities, but, significant decreases in antioxidant indices. However, post-treatment with N-3 or livolin corrected these deviations. Although there was evidence of the dose dependent effects of N-3, the high dose was not always the most effective. The histological results proved that livolin has a more hepatoprotective action than N-3, although the biochemical and haematological findings attested that both therapies have comparable effects. It was concluded that livolin proffers a more protective effect than N-3 in DF-induced hepatotoxicity.

A comparison of the effects of thymoquinone, silymarin and N-acetylcysteine in an experimental hepatotoxicity

This study investigated the effects of thymoquinone, silymarin, and N-acetylcysteine in a rat model with carbon tetrachloride (CCl4)-induced hepatotoxicity. Although numerous similar studies are available, we aimed to compare the efficacy of these agents by considering N-acetylcysteine as a reference compound. A total of 50 male Wistar albino rats were randomly designated as 5 groups: Group I, CCl4; group II, thymoquinone and CCl4; group III, silymarin and CCl4; group IV, N-acetylcysteine and CCl4; group V, control group. CCl4 was administered intraperitoneally at a dose of 1.5 mL/kg (a mixture of CCl4: olive oil, 1:2) twice a week. Thymoquinone was administered at a dose of 10 mg/kg, silymarin was administered at a dose of 100 mg/kg, and N-acetylcysteine was administered at a dose of 100 mg/kg by daily intraperitoneal injection. At the end of four weeks, blood and liver tests were analyzed. The results were evaluated statistically via the one-way ANOVA test. A p-value <0.05 was considered statistically significant. Thymoquinone, silymarin, and N-acetylcysteine improved the levels of alanine aminotransferase, tumor necrosis factor-α, platelet-derived growth factor-BB, and interleukin-6, which were increased by CCl4. Thymoquinone and silymarin showed the positive increase in liver glutathione levels. Thymoquinone, silymarin, and N-acetylcysteine improved blood total oxidant status. In the histological examinations of liver tissue, thymoquinone decreased necrosis, and inflammation. The most positive decrease in the α-smooth muscle actin-stained hepatic stellate cell count was only observed with thymoquinone. These findings suggest that thymoquinone, silymarin, and N-acetylcysteine have potential for the treatment of diseases causing liver injury. Among these agents, thymoquinone showed the best results on most of the parameters. Since TQ appears to be at least as effective as SM and NAC in our in-vitro study, we propose that it is time for clinical studies with thymoquinone on hepatotoxicity.

Hepatoprotective Effect of Metadoxine on Acetaminophen-induced Liver Toxicity in Mice.

Background:Metadoxine (pyridoxine pyrrolidone carboxylate) is considered to be a beneficial agent for the treatment of experimental hepatotoxicity due to alcohol, CCl4, and bile duct ligation. Hence, the therapeutic effect of metadoxine and N-acetylcysteine (NAC) as reference drug was investigated in mice exposed to acute hepatotoxicity induced by a single oral toxic dose of acetaminophen (650 mg/kg).Materials and Methods:Metadoxine (200 and 400 mg/kg) and NAC (300 mg/kg) were given orally (p. o.), 2 h after acetaminophen administration. Serum aminotransferases, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin, hepatic glutathione (GSH), and malondialdehyde (MDA) levels were determined for evaluating the extent of hepatotoxicity due to acetaminophen and its protection by metadoxine.Results:Findings indicated that metadoxine significantly reduced the level of serum ALT, AST, and ALP but not total bilirubin which increased by acetaminophen intoxication. Administration of metadoxine also attenuated oxidative stress by suppressing lipid peroxidation (MDA) and prevented the depletion of reduced GSH level which caused by acetaminophen toxicity. Besides, metadoxine ameliorated histopathological hepatic tissue injury induced by acetaminophen.Conclusion:In most parameters examined, the effect of metadoxine was comparable to NAC. Hence, metadoxine could be considered as a beneficial therapeutic candidate to protect against acute acetaminophen hepatotoxicity.

Licochalcone E protects against carbon tetrachloride‑induced liver toxicity by activating peroxisome proliferator-activated receptor gamma.

The present study aimed to investigate the hepatoprotective role of Licochalcone E (LCE) and its mechanism of action in a mouse model of carbon tetrachloride (CCl4)-induced liver toxicity. Hepatotoxicity was induced in Kunming mice via an intraperitoneal injection (IP) of CCl4, 10 ml/kg body weight, diluted with corn oil at a 1:500 ratio. LCE was administered once a day for 7 days (IP) as pretreatment at a dose of 5 mg/kg/day. The levels of C-reactive protein (CRP) and tumor necrosis factor (TNF)-α were analyzed to determine the inflammation status. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed using ELISA assays. Liver ultrastructure was observed via optical microscopy. The mRNA and protein expression levels of peroxisome proliferator-activated receptor (PPAR)γ, and nuclear factor (NF)-κB were assayed using quantitative polymerase chain reaction and western blot analysis, respectively. Pretreatment with LCE decreased levels of ALT, AST, CRP and TNF-α, and NF-κB expression in the experimental hepatotoxicity mice model induced by CCl4. In addition, LCE increased the expression of PPARγ and normalized the hepatic histoarchitecture. However, the effects of LCE were reversed by cotreatment with the PPARγ inhibitor GW9662. The present study suggests that LCE may be used for the treatment of hepatotoxicity, and primarily exhibits its protective role through a PPARγ/NF-κB-mediated pathway.

The Garcinia kola biflavonoid kolaviron attenuates experimental hepatotoxicity induced by diclofenac

This study sought to investigate the effects of kolaviron on diclofenac-induced hepatotoxicity in rats. Sixty male Wistar rats were divided into 6 groups of 10 rats each as follows: a control group that received oral propylene glycol and treatment groups that received diclofenac alone, diclofenac followed by Livolin Forte (a reference drug), or diclofenac followed by kolaviron at three different doses. At the end of the study period, five rats per group were sacrificed under ketamine hydrochloride anesthetic, 24h after treatment, while the other 5 rats in the group were allowed to recover for 2 weeks before being sacrificed. Liver enzyme activities, total bilirubin levels, and the concentrations of several pro-inflammatory cytokines were determined using plasma samples, while liver tissue samples were used for antioxidant analysis and histopathological examination.Compared with the control group, plasma liver enzyme activities, along with bilirubin levels, were higher in the groups that received diclofenac alone or diclofenac+the highest dose of kolaviron, respectively. These groups had higher plasma concentrations of pro-inflammatory cytokines than did the control group. However, the administration of Livolin Forte and kolaviron (at the lower doses) ameliorated diclofenac-induced hepatic injury by improving antioxidant status, preventing an increase in inflammatory mediators, decreasing malondialdehyde, and attenuating the adverse effect of diclofenac on hepatic tissues. In addition, there was a significant difference in the histological scores between the groups that received either diclofenac alone or diclofenac followed by the highest dose of kolaviron when compared with the other three groups (Livolin Forte or lower doses of kolaviron). In conclusion, kolaviron appears to be as effective as Livolin in attenuating DCLF-induced hepatotoxicity in rats. However, high doses of kolaviron seem to cause damage to the liver.

Hepatoprotective Potential of Green Tea Extract against Experimental Hepatotoxicity in Rats

An experimental study was conducted to evaluate the hepatoprotective effect of aqueous extract of Camellia sinensis or green tea extract and N-acetyl-L-cysteine in acetaminophen-induced hepatotoxicity in rats. Male Wistar rats (n=24) of 3 mon age were equally divided into 4 groups. Group 1 served as normal control. Hepatotoxicity was induced in the remaining three groups with oral administration of 500 mg/kg of acetaminophen from day 1 to day 3. Groups 2, 3 and 4 were subsequently administered orally with distilled water, 300 mg/kg of N-acetyl-L-cysteine and 100 mg/kg green tea extract, respectively for 11 days. Mean body weights and biomarkers of hepatotoxicity were estimated on days 0, 4 (confirmation of toxicity) 15 (at the end of treatment). Hematological parameters were evaluated on 4 and 15 d. Antioxidant profile and ATPase enzymes were assessed at the end of the experiment. Livers were subjected to histopathology and transmission electron microscopy after the sacrifice on day 15. Antioxidant profile, ATPase, hematological and serobiochemical parameters were significantly altered and histopathological changes were noticed in liver of toxic control group. These changes were reversed in groups 3 and 4 that were administered with N-acetyl-L-cysteine and green tea extract, respectively. The results of the present investigation enunciated that green tea extract has potent hepatoprotective activity, though N-acetyl-L-cysteine was found superior in restoring the pathological alterations in acetaminophen-induced hepatotoxicity in Wistar rats.

THU-278 - The Bile Acid Tauroursodeoxycholic Acid Cooperates with N-Acetylcysteine in the Treatment of Experimental Acetaminophen-Induced Hepatotoxicity

THU-278 - The Bile Acid Tauroursodeoxycholic Acid Cooperates with N-Acetylcysteine in the Treatment of Experimental Acetaminophen-Induced Hepatotoxicity

Oxidative Stress and Liver Morphology in Experimental Cyclosporine A-Induced Hepatotoxicity.

Cyclosporine A is an immunosuppressive drug used after organ's transplantation. The adverse effects on such organs as kidney or liver may limit its use. Oxidative stress is proposed as one of the mechanisms of organs injury. The study was designed to elucidate CsA-induced changes in liver function, morphology, oxidative stress parameters, and mitochondria in rat's hepatocytes. Male Wistar rats were used: group A (control) receiving physiological saline, group B cyclosporine A in a dose of 15 mg/kg/day subcutaneously, and group C the CsA-vehicle (olive oil). On the 28th day rats were anesthetized. The following biochemical changes were observed in CsA-treated animals: increased levels of ALT, AST, and bilirubin in the serum, statistically significant changes in oxidative stress parameters, and lipid peroxidation products in the liver supernatants: MDA+4HAE, GSH, GSSG, caspase 3 activity, and ADP/ATP, NAD+/NADH, and NADP+/NADPH ratios. Microscopy of the liver revealed congestion, sinusoidal dilatation, and focal hepatocytes necrosis with mononuclear cell infiltration. Electron microscope revealed marked mitochondrial damage. Biochemical studies indicated that CsA treatment impairs liver function and triggers oxidative stress and redox imbalance in rats hepatocytes. Changes of oxidative stress markers parallel with mitochondrial damage suggest that these mechanisms play a crucial role in the course of CsA hepatotoxicity.

Tissue oxidative stress induced by patulin and protective effect of crocin

Patulin (PAT) is a secondary toxic metabolite produced principally by Penicillium expansum. This mycotoxin is known to be teratogenic, mutagenic, immunotoxic and neurotoxic, and it has been shown to cause damage in several organs in laboratory animals. This study focuses on the prevention of experimental murine PAT-induced nephrotoxicity and hepatotoxicity. We investigate the ability of a natural product, crocin (CRO), to counteract the toxic effects of PAT. Pre-treatment of mice with CRO prevented PAT-induced oxidative damage in both liver and kidney. CRO reduced lipid peroxidation, protein oxidation and restored redox status by regulating the endogenous antioxidant enzymatic system. These data corroborate and extend findings in PAT-induced nephrotoxicity and hepatotoxicity, and further suggest that preventive effect of CRO towards other forms of PAT toxicity, including neurotoxicity, may be warranted.

The protective effect of vildagliptin in chronic experimental cyclosporine A-induced hepatotoxicity.

The study examined the effect of dipeptidyl peptidase-4 (DPP-4) inhibitor, vildagliptin, in cyclosporine (CsA)-induced hepatotoxicity. Rats were divided into 4 groups treated for 28 days: control (vehicle), vildagliptin (10 mg/kg, orally), CsA (20 mg/kg, s.c.), and CsA-vildagliptin group. Liver function was assessed by measuring serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltransferase (γGT), lactate dehydrogenase (LDH), and albumin, and histopathological changes of liver were examined. Oxidative stress markers were evaluated. Assessment of nuclear factor-kappa B (NF-κB) activity in hepatic nuclear extract, serum DPP-4, and expression of Bax and Bcl2 were also done. CsA-induced hepatotoxicity was evidenced by increase in serum levels of AST, ALT, and γGT; a decrease in serum albumin; and a significant alteration in hepatic architecture. Also, significant increase in thiobarbituric acid reactive substance (TBARS) and decrease in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione (GSH) levels, increased expression Bax proteins with deceased expression of Bcl2, and increased hepatic activity of NF-κB and serum DPP-4 level were observed upon CsA treatment. Vildagliptin significantly improved all altered parameters induced by CsA administration. Vildagliptin has the potential to protect the liver against CsA-induced hepatotoxicity by reducing oxidative stress, DPP-4 activity, apoptosis, and inflammation.

Effect of amlodipine, lisinopril and allopurinol on acetaminophen-induced hepatotoxicity in rats

BackgroundExposure to chemotherapeutic agents such as acetaminophen may lead to serious liver injury. Calcium deregulation, angiotensin II production and xanthine oxidase activity are suggested to play mechanistic roles in such injury. ObjectiveThis study evaluates the possible protective effects of the calcium channel blocker amlodipine, the angiotensin converting enzyme inhibitor lisinopril, and the xanthine oxidase inhibitor allopurinol against experimental acetaminophen-induced hepatotoxicity, aiming to understand its underlying hepatotoxic mechanisms. Material and methodsAnimals were allocated into a normal control group, a acetaminophen hepatotoxicity control group (receiving a single oral dose of acetaminophen; 750mg/kg/day), and four treatment groups receive N-acetylcysteine (300mg/kg/day; a reference standard), amlodipine (10mg/kg/day), lisinopril (20mg/kg/day) and allopurinol (50mg/kg/day) orally for 14 consecutive days prior to acetaminophen administration. Evaluation of hepatotoxicity was performed by the assessment of hepatocyte integrity markers (serum transaminases), oxidative stress markers (hepatic malondialdehyde, glutathione and catalase), and inflammatory markers (hepatic myeloperoxidase and nitrate/nitrite), in addition to a histopathological study. ResultsRats pre-treated with amlodipine, lisinopril or allopurinol showed significantly lower serum transaminases, significantly lower hepatic malondialdehyde, myeloperoxidase and nitrate/nitrite, as well as significantly higher hepatic glutathione and catalase levels, compared with acetaminophen control rats. Serum transaminases were normalized in the lisinopril treatment group, while hepatic myeloperoxidase was normalized in the all treatment groups. Histopathological evaluation strongly supported the results of biochemical estimations. ConclusionAmlodipine, lisinopril or allopurinol can protect against acetaminophen-induced hepatotoxicity, showing mechanistic roles of calcium channels, angiotensin converting enzyme and xanthine oxidase enzyme in the pathogenesis of hepatotoxicity induced by acetaminophen.

Humic acid and glucan: protection against liver injury induced by carbon tetrachloride.

Humic acids (HAs) have a rather pleiotropic presence, however, their biological effects are still unclear. In this study, we focused on possible hepatoprotective effects of either HA alone or in combination with β-glucan. Using a model of experimental hepatotoxicity caused by carbon tetrachloride (CCL4), we showed that both HA and the glucan-HA combination offered significant protection against hepatotoxicity, with the combination offering superior effects. Our biochemical observations were confirmed by histological evaluation. Based on the experimental data, we conclude that whereas HA has significant effects, the synergy with glucan offers superior effects.

Ameliorative effect of parsley oil (Petroselinum crispum) against alcohol-induced hepatotoxicity and oxidative stress

Objective The aim of the present study was to evaluate the protective role of parsley oil in experimental alcohol-induced hepatotoxicity. Materials and methods Alcohol-administered rats were pretreated with parsley oil (50 mg/kg body weight) three times per week for 3 weeks and alcohol (10%) three times per week (during the first 2 weeks of the experiment). Results It was found that alcohol led to a marked increase in serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transferase (γ-GT) activities. In terms of oxidative stress and the antioxidant defense system, the depleted hepatic glutathione content, glutathione-S-transferase, and catalase activities of alcohol-administered rats increased above normal levels as a result of pretreatment with parsley oil. However, whereas elevated lipid peroxidation was observed in alcohol-treated rats, pretreatment with parsley oil produced a detectable decrease in the lipid peroxidation level. Conclusion The natural plant components found in parsley could protect the liver against alcohol-induced hepatotoxicity and oxidative stress. However, further clinical studies are required to assess the safety and benefits of parsley oil in humans.

Effect of N-acetyl cysteine (NAC), an organosulfur compound from Allium plants, on experimentally induced hepatic prefibrogenic events in wistar rat

Aim of present study was to investigate the effect of NAC on experimental chronic hepatotoxicity models induced by carbon tetrachloride (CCl4) and thioacetamide (TAA). CCl4 toxicity was induced by administering 200μl CCl4 (diluted 2:3 in coconut oil)/100g body weight, p.o., twice weekly for 8 weeks. TAA toxicity was induced by administering 150mg/kg b. wt. of TAA i.p., twice weekly for 8 weeks. NAC treatment was started along with toxicants (CCl4 and TAA) for 8 weeks and continued for further 4 weeks. Self reversal group was kept without any treatment for 4 weeks after completion of toxicant treatments. Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), Bilirubin were measured in serum. Hydroxyproline (HP), lipid peroxidation (LPO), catalase (CAT), Glutathione peroxidase (GPx) and Glutathione (GSH) were determined in liver samples by colorimetric methods. Cytochrome P450 2E1 (CYP 450 2E1), activity was determined as hydroxylation of aniline in liver microsomes. General examination and histological analysis were also performed. Serum markers of liver damage (AST, ALT, ALP and Bilirubin) were increased by CCl4 and TAA intoxication (p<0.001), whereas co-treatment with NAC reversed such changes (p<0.001). HP was enhanced in toxicant groups (p<0.001 in CCl4 and TAA), but inhibited by NAC (p<0.001). LPO was increased while as GSH, CAT and GPx decreased by the administration of CCl4 and TAA (p<0.001); co-administration of NAC restored these liver markers to normal levels (p<0.001). Biochemical determinations were corroborated by general and histological findings. Keeping in view the biochemical and histopathological studies, it was concluded that CCl4 and TAA are strong hepatotoxic agents that produce liver fibrosis with close proximity to human etiology (micronodular cirrhosis) and NAC has a significant protective activity against CCl4 and TAA. NAC has also been validated as a model against oxidative burden in chronic liver pathology.

Hepatoprotective effect of Silybum marianum on experimental hepatotoxicity in broilers

Uncontrolled lipid oxidation plays a key role in poultry diseases. Silybum marianum have been used as a natural medication for the liver and biliary duct. Pharmacologically effective substance of silymarin includes four main ingredients: silybin, silychristin, silydianin, and isosilybin. CCL4, a hepatotoxic chemical agent, is largely used to produce experimental models to study hepatic cirrhosis and fibrosis in experimental animals. The aim of the present study was to verify the hepatoprotective effects of feed mixtures containing S. marianum in CCL4-induced hepatotoxicity in broilers. A randomized experimental design was used, and chicks were divided into six treatment groups. Chicks in group 1 (control) were fed basal diets without any supplementation. Birds in group 2 were fed basal diets and received CCL4. Birds in group 3 were fed basal diets supplemented with 60 ppm extract of S. marianum fruit (SE). Birds in groups 4 to 6 fed basal diet plus 40 ppm SE+CCL4, 60 ppm SE+CCL4, and 80 ppm SE+CCL4, respectively. Blood samples were analyzed to determine the contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), total protein, albumin, globulin, and liver cytochrome P450. In CCL4-treated groups, the mean serum levels of ALT, AST, SGOT, and SGPT were markedly (P < 0.05) raised compared to the control group, and addition of SE reduced (P < 0.05) the levels of these enzymes. Liver cytochrome P450 increased with CCL4 and reduced (P < 0.05) with the coadministration of different concentrations of SE (P < 0.05). It was observed that treatment with S. marianum fruit extract significantly reduced the tissue damage caused by CCL4.

Fumonisin B1: A Neurotoxic Mycotoxin / Fumonizin B1: Neurotoksični Mikotoksin

AbstractFumonisin B1 (FB1) is a mycotoxin produced by Fusarium spp. moulds that contaminate crop, predominantly maize, all around the world. More than 15 types of fumonisins have been indentified so far, but FB1 is the most abundant and toxicologically the most significant one. FB1 has a wide range of toxic effects, depending on animal species. In horses FB1 causes equine leukoencephalomalacia (ELEM), in pigs pulmonary oedema and in experimental rodents nephrotoxicity and hepatotoxicity. In humans exposure to FB1 is linked with higher incidence of primary liver cancer and oesophageal cancer, which are frequent in certain regions of the world (such as Transkei region in South Africa) where maize is staple food. The occurrence of neural tube defect in children in some countries of Central America (such as Mexico and Honduras) is connected with the consumption of FB1-contaminated maize-based food. However, possible involvement of FB1 in the development of human diseases is not clear. Nevertheless, the International Agency for Research on Cancer (IARC) has classified FB1 as a possible carcinogen to humans (group 2B).FB1 is a causative agent of ELEM, a brain disorder in equines, indicating that brain is a target organ of FB1 toxicity. Several studies on experimental animals or on cell cultures of neural origin have established that FB1 has a neurodegenerative potential, although the mechanism of its neurotoxicity is still vague. The aim of this article is to give an overview of available literature on FB1 neurotoxicity and involved mechanisms, and to offer a new perspective for future studies.

Pathogenesis of Liver Injury in Acute Liver Failure

Acute liver failure (ALF) represents the most severe damage an organ can sustain and can lead to shock, coagulopathy, altered mentation, cerebral edema, renal failure, infection, and, ultimately, multiorgan failure. The US Acute Liver Failure Study Group (ALFSG; available at: acuteliverfailure.org), convened a meeting on October 17 and 18, 2011, and included clinical, translational and fundamental investigators to discuss the pathogenesis of acute hepatocyte injury, how it occurs, and its downstream effects. The ALFSG has, for the past 14 years, carefully collected detailed clinical information and bio-samples from roughly 2000 patients with ALF at 24 tertiary medical centers across the United States. This meeting sought to summarize our current understanding of the pathogenetic factors that drive acute liver injury. These included consideration of (1) the contribution of innate immunity to liver injury, (2) the role of cytokine release in perpetuating liver injury and causing multiorgan failure, (3) mechanisms of apoptosis in ALF, (4) alterations in signal transduction with a focus on the role of c-Jun N-terminal kinase (JNK), (5) the contribution of infection to the pathogenesis of ALF, (6) the emerging centrality of inflammasome and sterile inflammation in the pathogenesis of ALF, (7) systems biology approaches to integrating and ordering the wide array of seemingly massively perturbed effectors in ALF, (8) host genetics and its contribution to ALF susceptibility, including a consideration of the power of next generation sequencing tools as they relate to ALF, and (9) contribution of liver regeneration to counteraction of ALF. Finally, we considered novel therapeutic strategies for ALF based on these pathogenetic concepts.

Evaluation of protective effect of Butea monosperma (lam.) Taub in experimental hepatotoxicity in rats.

Evaluation of protective effect of Butea monosperma (lam.) Taub in experimental hepatotoxicity in rats.

Tissue distribution of 35S-labelled perfluorooctane sulfonate in adult mice after oral exposure to a low environmentally relevant dose or a high experimental dose

The widespread environmental pollutant perfluorooctane sulfonate (PFOS), detected in most animal species including the general human population, exerts several effects on experimental animals, e.g., hepatotoxicity, immunotoxicity and developmental toxicity. However, detailed information on the tissue distribution of PFOS in mammals is scarce and, in particular, the lack of available information regarding environmentally relevant exposure levels limits our understanding of how mammals (including humans) may be affected. Accordingly, we characterized the tissue distribution of this compound in mice, an important experimental animal for studying PFOS toxicity. Following dietary exposure of adult male C57/BL6 mice for 1–5 days to an environmentally relevant (0.031 mg/kg/day) or a 750-fold higher experimentally relevant dose (23 mg/kg/day) of 35S-PFOS, most of the radioactivity administered was recovered in liver, bone (bone marrow), blood, skin and muscle, with the highest levels detected in liver, lung, blood, kidney and bone (bone marrow). Following high daily dose exposure, PFOS exhibited a different distribution profile than with low daily dose exposure, which indicated a shift in distribution from the blood to the tissues with increasing dose. Both scintillation counting (with correction for the blood present in the tissues) and whole-body autoradiography revealed the presence of PFOS in all 19 tissues examined, with identification of thymus as a novel site for localization for PFOS and bone (bone marrow), skin and muscle as significant body compartments for PFOS. These findings demonstrate that PFOS leaves the bloodstream and enters most tissues in a dose-dependent manner.

Experimental hepatotoxicity produced by ethinyl estradiol

Ethinyl oestradiol (EO) is the most commonly used as a component of oral contraceptive and hormonal replacement therapy (HRT) in women. However, its excessive and prolonged use may cause cytotoxicity, including cancer of many organs. Hence, the present study was performed to produce the experimental hepatotoxicity in female albino rats. EO was administered to different groups of rats, respectively @ 250, 500 and 750 μg/kg body weight, orally, weekly for 16 and 20 weeks. One group of rats was administered with saline alone to serve as control. The rats were sacrificed after their respective experimental periods, and the livers were collected and preserved in 10% buffered formalin. Later on, the histopathological study of liver tissues was done. On the 17th week, the hepatic tissues showed severe congestion, focal areas of hemorrhage, extreme vacuolation of cytoplasm, distended sinusoids with dilated central veins. Degeneration and necrosis of hepatocytes as evidenced by increased cytoplasmic granularity, and dissolution of nuclear materials were seen. On the 21st weeks, these changes were extremely severe and quite conspicuous. Distinct fibrosis was also noticed. EO caused hepatotoxicity, the extent and severity of which were dose and time dependent, indicating that this drug at higher dose after prolonged duration (500 or 750 μg/kg, orally, weekly for 20 weeks) may cause the standard experimental hepatotoxicity in rats.