Chloride Induced Hepatotoxicity In Rats Research Articles

Rhamnus alaternus aqueous extract enhances the capacity of system redox defence and protects hepatocytes against aluminum chloride toxicity in rats

BackgroundThis study was designed to evaluate the protective effects of a Rhamnus alaternus aqueous extract (RAAE) on aluminum chloride-induced hepatotoxicity in rats. A preliminary phytochemical study and antioxidant activity tests of the extract were performed.MethodsA preliminary phytochemical study and antioxidant activity tests of the extract were performed. For the in vivo study, twenty-four male rats were divided into four groups. The control group (C); the RAAE group treated with 250 mg/kg b.w RAAE; the AlCl3 group, which received 50 mg/kg b.w AlCl3; and the AlCl3/RAAE group that was treated with AlCl3 plus RAAE.ResultsThe RAAE contains several phenolic compounds. This plant extract showed a high radical scavenging effect and high antioxidant activity. Administration of AlCl3 resulted in a significant increase in the activities of aspartate aminotransferase and alanine aminotransferase (AST, ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) and significant decreases in the plasma concentrations of total proteins and albumin. Moreover, AlCl3 induced a hepatic pro-oxidant effect leading to an increase in malonaldehyde (MDA) and carbonyl protein contents, the depletion of the content of reduced glutathione (GSH) and a decrease in the antioxidant enzymatic activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). However, RAAE supplementation with AlCl3 treatment significantly decreased the levels of MDA and carbonyl proteins and markedly restored the activities of the antioxidant enzymes. These results are supported by the improvement in liver tissue restoration.ConclusionsThe Rhamnus alaternus aqueous extract was shown to have effective antioxidant activity owing to its phenolic compounds protecting against AlCl3-induced liver oxidative damage.

Rutin ameliorates mercuric chloride-induced hepatotoxicity in rats via interfering with oxidative stress, inflammation and apoptosis

ObjectiveMercury is a global environmental pollutant and is responsible for several organ pathophysiology including oxidative stress-induced liver disorders. Therefore, the present study was conducted to evaluate the potential ameliorative effects of rutin on mercury chloride (HgCl2)-induced hepatotoxicity in adult male rats. MethodsHgCl2 was intraperitoneally injected at a dose of 1.23 mg/kg body weight for 7 days alone or in combination with the orally rutin (50 and 100 mg/kg body weight). ResultsRutin treatment significantly improved liver function tests [alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT)], and increased activities of antioxidant defense system [catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx)] and glutathione (GSH) content. The histological alterations and epidermal growth factor receptor (EGFR) expression in the HgCl2-induced liver tissues were decreased by administration of rutin. Furthermore, rutin reversed the changes in levels of apoptosis and inflammation related proteins involving p53, Bcl-2 associated X protein (Bax), B-cell lymphoma-2 (Bcl-2), cytochrome c, nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), B-cell lymphoma-3(Bcl-3) and interleukin-1β (IL-1β), and inhibited p38α mitogen-activated protein kinase (MAPK) and cysteine aspartate specific protease-3 (caspase-3) activations. ConclusionThe data of the present study suggest that rutin effectively suppress HgCl2‐induced hepatotoxicity by ameliorating oxidative stress, inflammation and apoptosis.

Therapeutics potential of Ocimum basilicum following mercury chloride-induced hepatotoxicity in rats (Rattus norvegicus)

Globally mercury (Hg) has been reported as one of heavy metal of known toxicity, noted for inducing public health disasters. Present study examines the therapeutics potentials of Ocimum basilicum on mercury chloride (HgCl2) induced hepatotoxicity in Wistar rats. Thirty adult Wistar rats randomly divided into six groups (A-F) of five rats each. Group A served as control was given 2 mL/day of distilled water, Group B, C, D, E and F received 500 mg/kg body weight (bwt) of O. basilicum extract, 20 mg/kg/bwt of HgCl2, 40 mg/kg bwt of HgCl2, 20 mg/kg bwt of HgCl2 and 500 mg/kg bwt O. basilicum leave extract, 40 mg/kg bwt and 500 mg/kg bwt O. basilicum administered daily by gastric gavage, for 21 consecutive days. The gross anatomical parameters of the liver and liver histology were assessed. Liver oxidative stress was evaluated by liver superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH) and malondialdehyde (MDA) assays. The activities of the biomarker enzymes of the liver (alanine transaminase, aspartate transaminase and alkaline phosphatase were assayed). Histological profiles of the liver revealed derangement of the liver cytoarchitecture following consumption of mercury chloride and a marked improvement was observed after O. basilicum administration. Similarly, O. basilicum improved the reduction of antioxidant parameters (SOD, CAT, GPx and GSH) and the increased MDA caused by mercury chloride consumption. O. basilicum thus proffer protection against free radical mediated oxidative stress in mercury chloride-induced hepatotoxicity in rats.

Antioxidative effects of schidandrin B and green tea polyphenols against mercuric chloride-induced hepatotoxicity in rats.

In the present study, we investigated the hepatoprotective effects of schisandrin B (Sch B) and green tea polyphenols (GrTP), two natural antioxidants, against Hg hepatotoxicity. Fifty-six rats were randomly divided into four groups of fourteen animals in each group: control group, Hg-treated group, Sch B pretreated group, and GrTP pretreated group. HgCl2 injection increased Hg accumulation, pathological and ultrastructural injury, lactate dehydrogenase (LDH) level, alanine transaminase (ALT) level, apoptosis, reactive oxygen species (ROS) level, glutathione (GSH) level, and malondialdehyde (MDA) level. HgCl2 injection decreased glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities. Sch B and GrTP protected against Hg-induced dysfunction and liver injury by enhancing the antioxidant defense system. Our results indicate that Sch B and GrTP exert antioxidative effects against Hg-induced hepatotoxicity in rats.

Hepatoprotective and Antioxidant Activity of Rhizome of Podophyllum hexandrum against Carbon Tetra Chloride Induced Hepatotoxicity in Rats

ObjectiveTo test possible antioxidant activity of n-hexane extract of Podophyllum hexandrum under in vitro and in vivo conditions. MethodsThe in vitro antioxidant activity was evaluated by the ability of the extract to interact with the stable free radical DPPH, Superoxide (O2−), Hydroxyl (OH−), Hydrogen peroxide (H2O2) radicals, and reducing power ability of the extract was also evaluated. Under in vivo conditions the extract was evaluated for its hepatoprotective activity by measuring different biochemical parameters, such as serum alanine aminotransaminase, serum aspartate aminotransaminase and serum lactate dehydrogenase and antioxidant enzymes. Antioxidant status was estimated by determining the activities of antioxidative enzymes, glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and superoxide dismutase (SOD), and by determining the levels of reduced glutathione (GSH) and thiobarbituric acid reactive substances (TBARS). ResultsHexane extract of P. hexandrum exhibited good radical scavenging capacity in neutralization of DPPH, O2−, OH −, and H2O2 radicals in a dose dependent manner. n-hexane extract of Podophyllum hexandrum at the doses of 20, 30, and 50 mg/kg-day produced hepatoprotective effect by decreasing the activity of serum marker enzymes, while it significantly increased the levels of glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), super oxide dismutase (SOD), and glutathione-S-transferase (GST) in a dose dependant manner. The effect of n-hexane extract was comparable to that of standard antioxidant vitamin E. ConclusionThe extract of Podophyllum hexandrum possess free radical scavenging activity under in vitro conditions and could protect the liver tissue against CCl4 induced oxidative stress probably by increasing antioxidant defense activities.

Antinecroinflammatory effects of atorvastatin against carbon tetra chloride-induced hepatotoxicity in rats

Atorvastatin is widely used in the treatment of hepatic disease. The aim of present study is to determine the necroinflammatory activity of atorvastatin against CCl4 -induced hepatotoxicity in rats. 30 Adult Wistar male albino rats were collected and these rats divided randomly into 5 groups. Group I was as Control group and received intraperitoneal injection of saline (1mg.kg -1 ), Group II received CCl (1 mg/kg, s.c), Group III received Atorvastatin (5 mg/kg, p.o) +CCl (1 mg/kg, i.p), Group IV received Atorvastatin (10 mg/kg, p.o) +CCl (1 mg/kg, i.p) and Group V received Atorvastatin (15 mg/kg, p.o) +CCl (1 mg/kg, i.p) for 28 consecutive day. At the 28 day blood samples from all rats of every group were collected and levels of SGPT, SGOT, ALP and Bilirubin by standard kits were assayed. The liver tissues were taken for histopathological examination. From histopathological study in group I no abnormal changes were observed and in group II, III and IV different abnormal changes with different degrees consist of fatty change, lymphocytic infiltration, necrosis, congestion and hemorrhage were distinguished.in end for Group V no fatty change were observed and was similar to normal hepatocyte. The animals treated with CCl4 exhibited a significant (P<0.001) rise in SGOT, SGPT, ALP and bilirubin levels when compared to the control group. The results of this study clearly demonstrated that the atorvastatin exhibited potent hepatoprotective activity against CCl 4 -induced hepatic damage in rats. This may be due to their antioxidant and free radical scavenging properties. In this study, an increase in the activities of SGPT, SGOT, ALP and bilirubin in serum evidenced the CCl4 -induced hepatocellular damage because these are cytoplasmic in location and are released into the circulation after cellular damage.

Beneficial effect of Trichopus zeylanicus extract on mercuric chloride-induced hepatotoxicity in rats

The present study aimed to determine the effect of Trichopus zeylanicus leaf extract (TZ Et) on mercuric chloride (HgCl2)-induced liver toxicity in rats. Wistar albino male rats were divided into four groups. Group I was administered physiological saline as a vehicle control. Group II was administered HgCl2 (0.4 mg/kg body weight/day) intraperitoneally for 20 days. Groups III and IV were administered TZ Et orally (100 mg/kg body weight/day) for 20 days with or without intraperitoneal administration of HgCl2. Serum hepatic marker enzymes, enzymic and non-enzymic antioxidants, liver functional markers, lipid peroxidation, and liver histology were evaluated. The toxic effect of HgCl2 was indicated by the significantly (p<0.05) increased serum marker enzymes, liver functional markers, and lipid peroxidation. The activities of enzymic and non-enzymic antioxidants were significantly (p<0.05) decreased. TZ Et significantly (p<0.05) prevented these pathological alterations as observed by histology. The present study concludes that TZ Et has the ability to alleviate the hepatotoxic effects caused by HgCl2 in rats.

Effects of Eriobotrya japonica (Lindl.) flower extracts on mercuric chloride-induced hepatotoxicity in rats

Mercury (II) is an important factor in hepatotoxicity that can enter the body through marine diets and amalgams. In the present study, the protective effect of the Eriobotrya japonica flower extract (EJFE) on HgCl2-induced hepatotoxicity was investigated. Five mg/kg of mercuric chloride in drinking water was given to rats either with saline or EJFE (100 and 200 mg/kg as intraperitoneal (IP)) for 30 d. The mercury levels in different groups of liver tissues of the rats were measured with flameless atomic absorption spectroscopy (F-AAS). Also, mercury accumulation in the liver of the rats was modeled by using a parallel chemical kinetic model. The results showed that HgCl2-induced oxidative damage led to a significant decrease in glutathione (GSH) and the total antioxidant capacity (TAC) levels, and to a significant increase in lipid peroxidation level. Accumulated mercury was 14.47% more in the livers of the stress groups than in those of the control groups (P<0.001), whereas the amount of Hg was adjusted to 13.49% and 13.93% in groups treated with 100 and 200 mg/kg of EJFE respectively, as compared with stress groups (P<0.001). HPLC analysis of EJFE revealed that hesperetin and gallic acid are the major antioxidants in EJFE. Results demonstrate that flowers of the Eriobotrya japonica cause a significant protection against HgCl2 induced hepatotoxicity in all diagnostic parameters by strengthening the antioxidant defense mechanisms and they may have a therapeutic function in free radical mediated diseases.