Hepatotoxicity In Adult Rats Research Articles

Hepatoprotective and antioxidant effects of Octopus vulgaris extract against Depakine®-induced hepatotoxicity in adult rats

Background and objective Antiepileptic drug Depakine® is often used, although it can cause birth defects in both human and animals. This study’s goal was to assess the Octopus vulgaris extract’s (OE) ability to protect against the hepatotoxicity caused by Depakine in an effort to advance its clinical application. Patients and methods Four groups of adult male Wistar rats (150–180 g b.w.) have been designed at random (10 rats each) as: 1) healthy control group; 2) healthy rats treated orally with OE (50 mg/kg/day); 3) rats administrated orally with Depakine® (500 mg/kg/day); 4) rats treated with OE in combination with Depakine. Results and conclusion After 6 weeks of treatment, the results demonstrated that OE was effective in lowering Depakine®-induced hepatotoxicity. This was shown by a significant rise in liver glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) values as well as albumin and total protein levels. Additionally, there was a considerable drop in the serum levels of tumor necrosis alpha (TNF-α), interlukin-1beta (IL-1β), interlukin-4 (IL-4), interlukin-6 (IL-6), and interlukin-10 (IL-10), which exacerbated the structural recovery of the liver’s histological image. Conclusion: OE was highly effective in reducing the oxidative stress caused by Depakine® and protecting the liver from its toxic effects. OE is a viable supplement candidate for liver protection against the negative effects of that antiepileptic medication.

Ameliorative effect of costus ethanolic extract against Oxaliplatin-induced hepatotoxicity in adult rats

Ameliorative effect of costus ethanolic extract against Oxaliplatin-induced hepatotoxicity in adult rats

Glyphosate disrupts redox status and up-regulates metallothionein I and II genes expression in the liver of adult rats. Alleviation by quercetin.

The present work evaluated the possible protective effects of quercetin against glyphosate-induced hepatotoxicity in adult rats. Rats were randomly divided into three groups: a control group (C), a glyphosate-treated group (Gly) and a group treated with both glyphosate and quercetin (Gly+QE). During the experimental period (15 days), glyphosate (50 mg/kg b.w.) was administered every two days by intraperitoneal way while quercetin (20 mg/kg b.w./day) was administered daily by gavage. Glyphosate-induced hepatic oxidative stress was evidenced by the increased levels of malondialdehyde, hydrogen peroxide, advanced oxidation protein products and protein carbonyls with a significant decrease in enzymatic (superoxide dismutase, catalase, glutathione peroxidase) and non-enzymatic (non-protein thiols, glutathione, vitamin C) antioxidants. Plasma biomarkers of hepatotoxicity (AST, ALT, ALP, γ-GT, albumin) were also altered. Moreover, glyphosate induced DNA damage, up-regulated metallothionein (MT I and MT II) genes expression and provoked histopathological changes in rats' liver. Quercetin supplementation to glyphosate-treated rats markedly ameliorated all the parameters indicated above as well as the liver histoarchitecture. Therefore, quercetin might have beneficial effects against glyphosate-induced hepatotoxicity in rats.

The possible ameliorating effect of vitamin E on hyperthyroidism-induced hepatotoxicity in adult rats

Introduction Thyroid dysfunctions are frequently associated with abnormalities of liver tests and in severe forms with histologically hepatocellular damage. Aim of the work: This study was set to evaluate the ameliorating effect of vitamin E on the hyperthyroidism inducedhepatotoxicity. Materials and methods 36 male albino rats were used in this study and divided into four equal groups: Group I:control group Group II: rats received 100 mg vitamin E dissolved in oil, via gastric tube, for 30 days. Group III: rats were received l-thyroxin dissolved in distilled water daily at a dose of 100 µg/kg body weight, via an intragastric tube for 30 days. Group IV: rats received both l-thyroxin as group III plus vitamin E as in group II for 30 days. At the end of the experiment, blood samples were obtained for assessment of some biochemical parameters. Liver specimens were obtained and processed for light and electron microscopic study. Moreover, morphometric analysis of the portal veins, blood sinusoids and bile ducts diameter was done. Results A statistically significant elevation in the levels of T3 as well as, significant elevation of ALT and AST, a significant increase in the diameter of portal veins, blood sinusoids and bile ducts was observed in the group III. Stained sections of the liver of group III showed the majority of hepatocytes were vacuolated with dark nuclei and pale vacuolated cytoplasm. Mononuclear cellular infiltrate was observed around the dilated congested portal vessels and the congested central veins. Ultrastructural study of hepatocytes revealed degenerated mitochondria, dilated rER, sER and multiple lysosomes, depletion of glycogen granules. Furthermore, there was significant improvement of the biochemical and histological pictures toward the normal among the group IV. Conclusion Hyperthyroidism is toxic to the rat hepatocytes by oxidative stress. Therefore, addition of vitamin E to the hyperthyroid patients may be recommended.

Lipoic acid attenuates Aroclor 1260-induced hepatotoxicity in adult rats.

The present study was aimed to investigate the mechanistic aspect of Aroclor 1260-induced hepatotoxicity and its protection by lipoic acid. The adult male Albino rats were divided into six groups. Group I served as control. Group II received lipoic acid (35 mg/kg/day). Aroclor 1260 was given to rats by oral gavage at doses 20, 40, or 60 mg/kg/day (Groups III, IV, and V, respectively). Group VI was pretreated with lipoic acid (35 mg/kg/day) 24 h before Aroclor 1260 (40 mg/kg/day). Treatment in all groups was continued for further 15 consecutive days. Serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase activities and total bilirubin, total cholesterol, and triglycerides were significantly increased while total protein, total albumin, and high-density lipoprotein were significantly decreased. Hydrogen peroxide production and lipid peroxidation were significantly increased while superoxide dismutase and catalase activities and reduced glutathione (GSH) content was significantly decreased in liver. Caspase-3 & -9 activities were significantly increased in liver. Lipoic acid pretreatment significantly reverted all these abnormalities toward their normal levels. In conclusion, Aroclor 1260 induced liver dysfunction, at least in part, by induction of oxidative stress. Apoptotic effect of hepatic cells is involved in Aroclor 1260-induced liver injury. Lipoic acid could protect rats against Aroclor 1260-induced hepatotoxicity. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 913-922, 2016.

Effect of selenium on methimazole-induced liver damage and oxidative stress in adult rats and their offspring

This study aimed to investigate the protective effect of selenium (Se) on methimazole (MMI; an antithyroid drug)-induced hepatotoxicity in adult rats and their progeny. Female Wistar rats were randomly divided into four groups of six rats in each group: group I served as controls that received standard diet; group II received MMI in drinking water as 250mgL(-1) and standard diet; group III received both MMI (250mgL(-1), orally) and Se (0.5mgkg(-1) of diet); group IV received Se (0.5mgkg(-1) of diet) as sodium selenite. Treatments were started from the 14th day of pregnancy until day 14 after delivery. Exposure of rats to MMI promoted oxidative stress with an increase in liver malondialdehyde levels, advanced oxidation protein products and protein carbonyl contents and a decrease in the levels of glutathione, nonprotein thiols and vitamin C. A decrease in the activities of liver glutathione peroxidase, superoxide dismutase, catalase and lactate dehydrogenase and in the levels of plasma total protein and albumin was also observed. Plasma transaminase activities and total, direct and indirect bilirubin levels increased. Coadministration of Se through diet improved all biochemical parameters. The histopathological changes confirmed the biochemical results. Therefore, our investigation revealed that Se, a trace element with antioxidant properties, was effective in preventing MMI-induced liver damage.

Effects of selenium on chromium (VI)-induced hepatotoxicity in adult rats

Chromium, a major environmental pollutant, is known for its wide toxic manifestations. The present experiment pertains to the protective role of selenium (Se) against K 2Cr 2O 7-induced hepatotoxicity. Female Wistar rats were divided into four groups of six each: group I served as controls which received standard diet; group II received in drinking water K 2Cr 2O 7 alone (700 ppm); group III received both K 2Cr 2O 7 and Se (0.5 Na 2SeO 3 mg/kg of diet); group IV received Se (0.5 mg/kg of diet) for 3 weeks. Exposure of rats to chromium promoted oxidative stress with an increase in malondialdehyde (MDA) and a decrease in glutathione (GSH) levels. A decrease in glutathione peroxidase (GPx) and an increase in superoxide dismutase (SOD) and catalase (CAT) activities were observed. Se supplementation to the diet of group III improved all the parameters cited above. Yet, plasma transaminases (AST and ALT), lactate dehydrogenase (LDH) activities, cholesterol, triglycerides (TG) and low density lipoprotein-cholesterol (LDL-C) levels increased, while high density lipoprotein-cholesterol (HDL-C) decreased. Co-administration of Se to the diet of group III restored hepatic markers to near-normal values. The biochemical results confirmed the histopathological findings. Therefore, our investigation revealed that Se was effective in preventing K 2Cr 2O 7-induced hepatotoxicity.

Cobalt chloride induces hepatotoxicity in adult rats and their suckling pups

To assess liver damages in pregnant and lactating rats and in their suckling pups, wistar female rats were given through drinking water 350 ppm of CoCl 2 (157 ppm Co 2+) from the 14th day of pregnancy until day 14 after delivery. The effects of cobalt chloride on lipid peroxidation levels, antioxidant enzyme activities, lipid profile and histopathology aspects of liver were evaluated. Biochemical results showed that lipid peroxidation increased significantly in Co-treated rats, as evidenced by high liver thiobarbituric acid-reactive substance (TBARS) levels. Alteration of the antioxidant system in treated group was confirmed by the significant decline of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities and reduced glutathione (GSH) content in liver of suckling pups and their mothers. Moreover, CoCl 2 exposure induced an increase in the activities of the aspartate transaminase (AST), alanine transaminase (ALT), lactate deshydrogenase (LDH) and bilirubin levels in pups and their mothers while liver LDH activity and plasma albumin level were significantly decreased. On the other hand, cobalt chloride induced a marked hypoglycemia, a significant decline in triglycerides and total cholesterol levels. Histological studies showed an infiltration of mononuclear cells and vascular congestion in liver of pups and their mothers. Based on the present findings, exposure of rats to CoCl 2 during late pregnancy and early postnatal period affects antioxidant enzyme activities and lipid peroxidation indicating liver damage in mothers and their offspring.