Radical scavenging abilities and hepatoprotective effect of [N,N′-Bis (salicylidene) ethane-1, 2-diaminato] oxovanadium (IV) complex in CCl4-treated rats

The antioxidant activity of [N, N′-Bis (salicylidene) ethane-1, 2-diaminato] oxovanadium (IV) complex (VO-salen complex) was evaluated using different in vitro evaluating systems including superoxide anion (O₂^?) and hydrogen peroxide (H₂O₂) scavenging activities. In addition, the inhibitory effects of this compound on protein oxidation and inhibition of Fe²⁺/ascorbate-induced lipid peroxidation were studied using rat liver homogenate. In vitro results revealed that the VO-salen complex has strong inhibitory effects on protein oxidation and lipid peroxidation of the liver homogenate along with a concentration-dependent quenching of H₂O₂ and O₂^? radicals. In an in vivo approach, hepatoprotective potential of the VO-salen complex against liver damages induced by CCl₄ treatment was also investigated. After intraperitoneal injection of CCl₄ to rats, various biochemical changes associated with liver injury and/or oxidative stress were measured. The results showed that the sera levels of ALT, AST, ALP and the content of hepatic thiobarbituric acid reactive substances (TBARS) were all increased and the glutathione (GSH) content and the hepatic superoxide dismutase (SOD) and catalase (CAT) activities were decreased in CCl₄-treated rats. However, simultaneous treatment of rats with VO-salen (0.6 mg/kg) and CCl₄ significantly attenuated the sera levels of ALT, AST, ALP and the hepatic TBARS content. In addition, by VO-salen therapy, the hepatic SOD and CAT activities and the GSH content were all restored back almost to their normal levels. The liver damages were also significantly ameliorated as compared to the CCl₄-treated rats. Based on these results, the VO-salen complex might be considered as an effective antioxidant and hepatoprotective agent suitable for further biological evaluation.     

Mangiferin, a natural polyphenol protects the hepatic damage in mice caused by CCl4 intoxication

Mangiferin is a natural polyphenolic (C-glucoxyl xanthone) antioxidant present in the bark, fruits, roots and leaves of Mangifera indica Linn. In the present study, we investigated the protective effect of mangiferin against carbon tetrachloride (CCl₄)-induced hepatotoxicity in mice and compared it with silymarin, a standard hepatoprotective drug. The pretreatment of mangiferin (30?mg/kg body weight, i.p.) has shown it to possess a significant protective effect by lowering the serum aspartate and alanine aminotransferases, alkaline phosphatase, bilirubin and inflammatory mediator TNF-α. This hepatoprotective action was confirmed by histological observation. In addition, pretreatment of mangiferin prevented the elevation of hepatic malondialdehyde formation and the depletion of antioxidant status (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, and total reduced glutathione) activity in the liver of CCl₄-injected mice. The results suggest that mangiferin exhibits potent hepatoprotective effects on CCl₄-induced liver damages in mice.     

Resolvin D1 attenuates CCl4-induced acute liver injury involving up-regulation of HO-1 in mice

Acute hepatic failure involves in excessive oxidative stress and inflammatory responses, leading to a high mortality due to lacking effective therapy. Resolvin D1 (RvD1), an endogenous lipid mediator derived from polyunsaturated fatty acids, has been shown anti-inflammatory and anti-oxidative actions, however, whether RvD1 has protective effects on hepatic failure remains elusive. In this study, the roles and molecular mechanisms of RvD1 were explored in carbon tetrachloride (CCl₄)-induced acute liver injury. Our results showed that RvD1 protected mice against CCl₄-induced hepatic damage, as evaluated by reduced aminotransferase activities and malondialdehyde content, elevated glutathione and superoxide dismutase activities, and alleviated hepatic pathological damage. Moreover, RvD1 significantly attenuated serum tumor necrosis factor-α and interleukin-6 levels as well as hepatic myeloperoxidase activity, whereas enhanced serum IL-10 level in CCl₄-administered mice. Further, RvD1 markedly up-regulated the expression and activity of heme oxygenase-1 (HO-1). However, inhibition of HO-1 activity reversed the protective effects of RvD1 on CCl₄-induced liver injury. These results suggest that RvD1 could effectively prevent CCl₄-induced liver injury by inhibition of oxidative stress and inflammation, and the underlying mechanism may be related to up-regulation of HO-1.     

Hepatocytes are protected by herb Phyllanthus niruri protein isolate against thioacetamide toxicity.

The herb, Phyllanthus niruri has been known to possess protective activity against various drugs and toxins induced hepatic disorders. Present study was conducted to evaluate the role of the protein isolate of the herb against thioacetamide (TAA)-induced cytotoxicity in mice hepatocytes. In vitro cell viability, lactate dehydrogenase (LDH) and alanine amino transferase (ALT) leakage were measured as the indicators of cell damage. In addition, measurement of the level of non-protein thiol, glutathione (GSH); activities of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST) as well as the extent of lipid peroxidation were carried out to evaluate the prooxidant-antioxidant status of the cell. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay was performed to determine the radical scavenging activity of the protein isolate. Results showed that the administration of the protein isolate prior to TAA exposure significantly reduced the release of LDH and ALT leakage and enhanced the cell viability in a dose-dependent manner in hepatocytes. Besides, the protein isolate appeared to prevent the alterations in GSH levels and activities of the anti-oxidant enzymes related to prooxidant-antioxidant status of hepatocytes. It also reduced the TAA-induced lipid peroxidation significantly as demonstrated by the reduction of malondialdehyde (MDA) production. DPPH radical scavenging assay showed that the protein isolate possessed radical scavenging activity. Combining, the data suggest that the protein isolate could protect hepatocytes from TAA-induced cellular injury probably by its antioxidative and radical scavenging properties.     

Antioxidant effects of Citharexylum spinosum in CCl4 induced nephrotoxicity in rat

The present study was carried out to evaluate the antioxidant effect of the chloroform extract of Citharexylum spinosum (CSCE) (Family: Verbenaceae) leaves in Sprague–Dawley male rats. The different groups of animals were administered with carbon tetrachloride (CCl₄; 20% in olive oil, 2 ml/kg body weight) 7 doses (i.p.) at 48 h interval. The CSCE at the doses of 100 and 200 mg/kg or silymarin at a dose of 50 mg/kg were administered intragastrically after 24 h to the CCl₄ treated rats. The effect of CSCE or silymarin on urine and serum markers (urea, creatinine, creatinine clearance, protein, albumin, urobilinogen and nitrite) was measured in CCl₄-induced nephrotoxicity in rat. Further, the effects on lipid peroxidation (TBARS), enzymatic antioxidants (catalase, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase) and non-enzymatic antioxidant glutathione (GSH) were estimated in the kidney samples. The CSCE and silymarin produced significant renal protective effects by restoring the concentration of urine and serum markers. Activity level of antioxidant enzymes and GSH contents were increased while lipid peroxidation (TBARS) was decreased, dose dependently with CSCE and silymarin. Decrease in body whereas increase in kidney weight induced with CCl₄ was restored with CSCE and silymarin. Chemical composition of CSCE indicated the presence of flavonoids, terpenoids, alkaloids and very low amount of saponins. Total flavonoids estimated were (127 ± 14.6) as rutin equivalent mg/g of the extract. From these results, it is suggested that CSCE possesses potent nephroprotective and antioxidant properties.     

Amelioration of CCl4-induced nephrotoxicity by Oxalis corniculata in rat

CCl₄ induces oxidative stress in various tissues by altering antioxidant enzymes defense system. In this study we investigated the chemical composition and protective role of Oxalis corniculata methanol extract (OCME) on CCl₄-induced nephrotoxicity in rat. Presence of flavonoids, alkaloids, terpenoids, saponins, cardiac glycosides, phlobatannins and steroids was determined in OCME while tannins were absent. Total phenolic contents estimated were 7.76 ± 0.36 (mg gallic acid equivalents/g extract) while total flavonoid contents recorded were 6.92 ± 0.52 (mg rutin equivalents/g extract). Intraperitoneal injection of CCl₄ (1 ml/kg b.w., 20% in olive oil) once a day for seven days caused nephrotoxicity as evident by elevated levels of urinary specific gravity, RBCs, WBCs, creatinine, protein, urobilinogen and nitrite. Serum level of creatinine, urea, blood urea nitrogen were significantly increased while protein and creatinine clearance was decreased by CCl₄ treatment in kidney samples. Activity of antioxidant enzymes; catalase, peroxidase, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase and glutathione concentration was decreased whereas lipid peroxidation and protein contents were increased along with histopathological injuries. Treatment with OCME caused significant recovery in changed parameters. It could be concluded that OCME has a protective role against CCl₄-induced oxidative stress in rat, due to antioxidant effects of phenolics.     

Pharmacological modification of endogenous antioxidant enzymes by ursolic acid on tetrachloride-induced liver damage in rats and primary cultures of rat hepatocytes.

The purpose of this study was to investigate possible protective effects of ursolic acid against CCl4-induced alterations of antioxidant defence enzymes in vivo as well as its effects against CCl4-intoxication in vitro. Pre-treatment of rats with ursolic acid significantly reduced serum levels of glutamate-oxalate-transaminase and glutamate-pyruvate-transaminase previously increased by administration of CCl4. Treatment with ursolic acid also significantly reversed the decreased superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase activities and glutathione levels in the liver, as the concentration of reduced glutathione was increased and the content of oxidized glutathione decreased in ursolic acid treated groups. Levels of lipid peroxidation were higher in the CCl4 group but the increase was also reduced after drug treatment (p < 0.01 for 1, 2.5 and 5 mmol/kg). In vitro results indicated that addition to the culture medium of ursolic acid (p < 0.01 for 500 microM) resulted in a reduction of glutamate-oxalate-transaminase, lactate dehydrogenase activities and in a good survival rate for the CCl4-intoxicated hepatocytes. Ursolic acid also ameliorated lipid peroxidation in primary cultured rat hepatocytes exposed to CCl4, as demonstrated by a reduction in malondialdehyde production. Moreover, ursolic acid (50-500 microM) showed radical scavenging properties in terms of hydroxyl formation. The results obtained suggest that ursolic acid treatment can normalize the disturbed antioxidant status of rats intoxicated with CCl4 by maintaining the levels of glutathione and by inhibiting the production of malondialdehyde due to its radical scavenging properties.     

Date Seed Oil Inhibits Hydrogen Peroxide-Induced Oxidative Stress in Normal Human Epidermal Melanocytes

The administration of antioxidants has been shown to enhance repair and healing processes in cutaneous tissue. Date seed oil (DSO) extract, which might be a potential source of natural antioxidants such as phenols and tocopherols, has been reported to be beneficial in the reduction of chemically induced oxidative stress in normal human skin. In this study, we investigated the protective effects of DSO against hydrogen peroxide (H₂O₂)-induced oxidative stress in terms of lipid peroxidation, depletion of such endogenous antioxidant defense enzymes as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) using normal human epidermal melanocytes (NHEM). The results showed that DSO, endowed with a radical scavenging ability, decreased oxidative injury by inhibition of damage caused by H₂O₂. Treatment of NHEM with DSO inhibited H₂O₂-induced lipid peroxidation. In addition, the extract inhibited H₂O₂-induced depletion of antioxidant defense components, such as SOD, CAT, and GPx. Our findings demonstrate that DSO is an efficient extract able to prevent melanocytes oxidative damage induced by H₂O₂ exposure. Thus it may be a potential promising candidate, as a chemopreventive agent, in the development of melanocyte-related pathologies like vitiligo and melanoma.     

Boschniakia rossica prevents the carbon tetrachloride-induced hepatotoxicity in rat

The present study was undertaken to investigate the hepatoprotective effect of Boschniakia rossica extract (BRE), rich in phenylpropanoid glycoside and iridoid glucoside, on CCl₄-induced liver damage. Male Wistar rats were randomly divided into six groups of ten each. While the first group was maintained as normal control, groups II–VI were administered 0.5 ml/kg CCl₄ (model), 100 mg/kg BRE plus CCl₄, 200 mg/kg BRE plus CCl₄, 50 mg/kg silymarin plus CCl₄ and 200 mg/kg BRE, respectively. CCl₄ challenge not only elevated the serum marker enzyme activities and reduced albumin (ALB) level but also increased liver oxidative stress, as evidenced by elevated lipid hydroperoxide (LOOH) and malondialdehyde (MDA) concentrations, combined with suppressed potential of hepatic antioxidative defense system including superoxide dismutase (SOD), glutathione peroxidase (GPx) activities and reduced glutathione (GSH) content. Furthermore, serum tumor necrosis factor-α (TNF-α), hepatic nitrite level, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein contents were elevated while cytochrome P450 2E1 (CYP2E1) expression and function were inhibited. Preadministration of BRE not only reversed the significant changes in serum toxicity markers, hepatic oxidative stress, xenobiotic metabolizing enzymes and proinflammatory mediators induced by CCl₄ but also restored liver CYP2E1 level and function. Interestingly, the protein expression of heme oxygenase-1 (HO-1) was further elevated by BRE treatment, which was markedly increased after CCl₄ challenge. These results demonstrate that BRE exhibits protective effect on CCl₄-induced acute hepatic injury via, at least in part, reduced oxidative stress, suppressed inflammatory responses and induced HO-1 protein expression combined with improved CYP2E1 level and function in liver.     

N-acetylcysteine protects against liver injure induced by carbon tetrachloride via activation of the Nrf2/HO-1 pathway

Chronic liver injury is an important clinical problem which eventually leads to cirrhosis, hepatocellular carcinoma and end-stage liver failure. It is well known that cell damage induced by reactive oxygen species (ROS) is an important mechanism of hepatocyte injure. N-acetylcysteine (NAC), a precursor of glutathione (GSH), is well-known role as the antidote to acetaminophen toxicity in clinic. NAC is now being utilized more widely in the clinical setting for non-acetaminophen (APAP) related causes of liver injure. However, the mechanisms underlying its beneficial effects are poorly defined. Thus, Aim of the present study was to investigate potential hepatic protective role of NAC and to delineate its mechanism of action against carbon tetrachloride (CCl₄)-induced liver injury in models of rat. Our results showed that the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities as well as malondialdehyde (MDA) contents decreased significantly in CCl₄-induced rats with NAC treatment. GSH content and superoxide dismutase (SOD) activities remarkably increased in the NAC groups compared with those in CCl₄-induced group. Treatment with NAC had been shown to an increase in nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) mRNA levels. In conclusion, these results suggested that NAC upregulated HO-1 through the activation of Nrf2 pathway and protected rat against CCl₄-induced liver injure. The results of this study provided pharmacological evidence to support the clinical application of NAC.     

Hepatoprotective Properties of Aqueous Leaf Extract of Persea Americana,Mill (Lauraceae) ‘Avocado’ Against CCL4-Induced Damage in Rats

Background

Natural products from plants have received considerable attention in recent years due to their diverse pharmacological properties, including antioxidants and hepatoprotective activities. The protective effects of aqueous extract of Persea americana (AEPA) against carbon tetrachloride (CCl₄)-induced hepatotoxicity in male albino rats was investigated.

Materials and Methods

Liver damage was induced in rats by administering a 1:1 (v/v) mixture of CCl₄ and olive oil [3 ml/kg, subcutaneously (sc)] after pre-treatment for 7 days with AEPA. Hepatoprotective effects of AEPA was evaluated by estimating the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and levels of total bilirubin (TBL). The effects of AEPA on biomarkers of oxidative damage (lipid peroxidation) and antioxidant enzymes namely, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione S-transferase (GST) were measured in liver post mitochondrial fraction.

Results

AEPA and Reducdyn® showed significant (p<0.05) hepatoprotective activity by decreasing the activities of ALT, AST, ALP and reducing the levels of TBL. The activities of antioxidant enzymes, levels of malondialdehyde and protein carbonyls were also decreased dose-dependently in the AEPA-treated rats. Pre-treatment with AEPA also decreased the serum levels of glutathione significantly.

Conclusion

These data revealed that AEPA possesses significant hepatoprotective effects against CCl₄-induced toxicity attributable to its constituent phytochemicals. The mechanism of hepatoprotection seems to be through modulation of antioxidant enzyme system.     

Hepatoprotective effects of Vernonia amygdalina (astereaceae) in rats treated with carbon tetrachloride

The possible modulatory effect of methanolic extract of Vernonia amygdalina (MEVA), a plant widely consumed in the tropics and used locally in the treatment of fever, jaundice, stomach disorders and diabetes on the toxicity of CCl₄, was investigated in male rats.Oral administration of CCl₄ at a dose of 1.2 g/kg body weight 3 times a week for 3 weeks significantly induced marked hepatic injury as revealed by increased activity of the serum enzymes ALT, AST, SALP and γ-GT. Methanolic extract of V. amygdalina administered 5 times a week for 2 weeks before CCl₄ treatment at 250 and 500 mg/kg doses of the extract ameliorated the increase in the activities of these enzymes. Likewise the methanolic extract of V. amygdalina reduced the CCl₄-induced increase in the concentrations of cholesterol, triglyceride and phospholipid by 37.8%, 30.6% and 8.5%, respectively, and a reduction in the cholesterol/phospholipids ratio. These parameters were however increased at 750 mg/kg extract pretreatment. CCl₄-induced lipid peroxidation was likewise attenuated by 57.2% at 500 mg/kg dose of the methanolic extract of V. amygdalina. Similarly, administration of the extract increased the activities of the antioxidant enzymes: superoxide dismutase, glutathione S-transferase and reduced glutathione concentration significantly at 500 mg/kg (P<0.05) and catalase activity at 500–1000 mg/kg doses. These results suggest that methanolic extract of V. amygdalina leaves posseses protective effect against CCl₄-induced hepatotoxicity by the antioxidant mechanism of action.     

Attenuation of CCl4-induced hepatic oxidative stress in rat by Launaea procumbens

Antioxidant effects of Launaea procumbens methanol extract (LPME) were evaluated against CCl₄-induced oxidative stress in liver of rat. 48 male rats were equally divided in to 8 groups (06 rats each). Group I (control) remained untreated, while Group II was given vehicles (olive oil and DMSO). Animals of Groups III, IV, V, VI and VII were injected intraperitoneally with CCl₄ (3 ml/kg b.w.; i.p., 20% CCl₄/olive oil) twice a week for four weeks. Group III received only CCl₄ while Group IV was given rutin (50 mg/kg b.w.). Group V, VI and VII were administered LPME at a dose of 100, 150 and 200 mg/kg b.w., respectively. Animals of Group VIII received LPME (200 mg/kg b.w.) alone. Oxidative stress induced with CCl₄ in liver was evident by a significant increase in triglycerides, total cholesterol, LDL-cholesterol, and enzymatic activities of AST, ALT, ALP, LDH, γ-GT activities in serum. Level of lipid peroxidation, nitrite, and hydrogen peroxide concentration, DNA injuries in liver samples was also increased with CCl₄. GSH concentration in liver was significantly decreased, as were the activities of antioxidant enzymes; CAT, POD, SOD, GSH-Px, GST, GSR, QR. Co-treatment of rats with LPME and rutin prevented all the changes observed with CCl₄. Hepatic lesions and telomerase activity induced with CCl₄ was also suppressed with LPME and rutin. It is suggested that LPME effectively prevented the CCl₄-induced oxidative injuries in liver, possibly through antioxidant and/or free radical scavenging effects of flavonoids and phenolic compounds in the extract.     

Danshensu-mediated protective effect against hepatic fibrosis induced by carbon tetrachloride in rats

The culprit of hepatic fibrosis (HF) is linked to suprathreshold deposition of collagen. Thus, collagen reduction by improved metabolism contributes to HF management. In this study, we aimed to investigate the hepatoprotective effects of Danshensu (DSS) against carbon tetrachloride (CCl₄)-induced HF rats. The results showed that DSS-administrated rats resulted in decreasing in hepatosomatic indexes, and lowering serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Meanwhile, the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) were increased, while the content of malonaldehyde (MDA) was lessened in liver tissue of DSS administration group. In addition, the pro-fibrotic markers of hydroxyproline (Hyp), type III procollagen (PCIII) and hyaluronic acid (HA) contents were decreased. Histopathological examination confirmed that the hepatotoxicity in CCl₄-injured rats was alleviated following the DSS administration. Furthermore, intrahepatic protein expressions of alpha-smooth muscle actin (α-SMA), phosphorylated JAK2 (p-JAK2) and phosphorylated STAT3 (p-STAT3) were effectively down-regulated, respectively. Overall, this work demonstrates that DSS played the protective effect against CCl₄-induced cytotoxicity in liver tissue, which the probable mechanism is associated with attenuation of lipid peroxidation, collagen accumulation and enhancement of anti-oxidative defense capability, as well as regulation of intrahepatic JAK/STAT pathway for maintaining collagenic homoeostasis.     

Carbon tetrachloride-induced early biochemical alterations but not necrosis in pigeon's liver

In contrast to what is well known to occur in rats, pigeons recelving CCl₄ (1 ml/kg i.p.) were not susceptible to necrogenic effects of the hepatotoxin at 24 h. There were, such as depression of glucose 6 phosphatase activity, decrease in the cytochrome P-450 content and in aminopyrine-N-demethylase activity in pigeon liver microsomes at 3 and 6 h after CCl₄ administration. Pigeon liver was able to activate CCl₄ to reactive metabolites that bind covalently to lipids, but no CCl₄-induced lipid peroxidation was proved by the diene hyperconjugation technique in pigeon liver microsomes at 1, 3 or 6 h after administration. Results suggest that covalent binding of CCl₄-reactive metabolities are more relevant to early biochemical alterations induced by CCl₄ than is lipid peroxidation. Absence of CCl₄-induced necrosis in pigeon liver could be attributabie to a smaller intensity of covalent binding interactions observed, when compared to susceptible specles, and to absence of lipid peroxidation.     

Hepatoprotective effect of acetonic and methanolic extracts of Heterotheca inuloides against CCl4-induced toxicity in rats

A model of hepatotoxicity by carbon tetrachloride (CCl₄) in rats was used in order to evaluate the protective potential of the acetonic and methanolic extracts of Heterotheca inuloides. Pretreatment with the two H. inuloides extracts attenuated the increase in the activity of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) observed in CCl₄-induced liver injury. The protective effect was confirmed by the analysis of tissue slides stained with hematoxylin-eosin and periodic acid/Schiff’s reagent. Additionally, the two extracts are scavengers to the superoxide radical as was observed by electron paramagnetic resonance. Due to the fact that the methanolic extract resulted in a better protective effect in the previous experiments, it was used to investigate in more detail the mechanism of hepatoprotection. Quercetin, one of the main components of the extract, with known hepatoprotective and antioxidant activity was used as a positive control. Pretreatment of animals with the methanolic extract or quercetin, was associated with the prevention of 4-hydroxynonenal and 3-nitrotyrosine increase in the liver, two markers of oxidative stress. Furthermore, the decrease in the activity of several antioxidant enzymes including superoxide dismutase, catalase and glutathione peroxidase in CCl₄-induced liver injury was alleviated by the pretreatment with H. inuloides methanolic extract or quercetin. These results suggest that the hepatoprotective capacity of H. inuloides methanolic extract is associated with its antioxidant properties, which would also explain the biomedical properties attributed to this plant.     

Arjunolic acid attenuates arsenic-induced nephrotoxicity.

Arsenic is highly toxic naturally occurring element that affects numerous organ systems in humans. Present study was designed to investigate the preventive role of a triterpenoid saponin, arjunolic acid (AA) against arsenic-induced nephrotoxicity in mouse model. For this study, NaAsO(2) was chosen as the source of arsenic. Oral administration of NaAsO(2) at a dose of 10mg/kg body weight for 2 days caused significant accumulation of arsenic in renal tissues as well as altered the activities of serum markers, urea nitrogen (UN) and creatinine, antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione reductase (GR) and glutathione peroxidase (GPx), level of cellular metabolites, reduced glutathione (GSH), oxidized glutathione (GSSG) and total thiols, level of lipid peroxidation end products and protein carbonyl content. Treatment with AA at a dose of 20mg/kg body weight for 4 days almost normalized above indices. Histological studies also indicated preventive role of AA against NaAsO(2)-induced nephrotoxicity. The radical scavenging activity and in vivo antioxidant power of AA were determined from its DPPH radical scavenging ability and ferric reducing/antioxidant power (FRAP), respectively. A well-known antioxidant, vitamin C was used as positive control throughout the study. Combining all, results suggest that arsenic could cause kidney damage by inducing oxidative stress in mice and that could be prevented by AA.     

Antagonism by chloramphenicol of carbon tetrachloride hepatotoxicity: Examination of microsomal cytochrome P-450 and lipid peroxidation

Administration of chloramphenicol early in CCl₄ intoxication prevents lipid peroxidation of endoplasmic reticulum membranes. Conversely, a sulfamoyl analog, Tevenel, was ineffective in preventing the lipoperoxidative process. Likewise, in an in vitro microsomal system chloramphenicol inhibited a lipid peroxidation process and Tevenel did not. However, both compounds bind to cytochrome P-450. Chloramphenicol did not maintain cytochrome P-450 levels after CCl₄ administration nor did it depress cytochrome P-450 levels in untreated animals. The data obtained indicate that chloramphenicol may prevent lipid peroxidation either by inhibiting CCl₄ metabolism or by acting as a free radical sequestering agent.