Methionine-supplemented diet augments hepatotoxicity and prooxidant status in chronically ethanol-treated rats

The purpose of this study was to investigate whether high methionine (HM) diet may influence the development of ethanol-induced hepatotoxicity and prooxidant–antioxidant balance in the liver. Rats received drinking water containing ethanol (20% v/v) and/or methionine supplemented diet (2% w/w) for 75 days. Although prooxidant–antioxidant balance did not change in the liver of rats in HM group, ethanol treatment was observed to increase plasma transaminase activities, and malondialdehyde (MDA) and protein carbonyl (PC) levels, but not glutathione (GSH), vitamin E and vitamin C levels, and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities in the liver of rats as compared to controls. However, ethanol plus HM diet caused further increases in plasma transaminase activities and hepatic MDA and PC levels. In addition, SOD, GSH-Px and GST activities were observed to decrease, but GSH, vitamin E and vitamin C levels remained unchanged in the liver as compared to ethanol, HM and control groups. Our results show that HM diet may augment hepatotoxicity and oxidative stress in the liver of chronically ethanol-treated rats.     

Increased lipid peroxidation in the liver and kidney and their mitochondrial fractions following buthionine sulfoximine induced glutathione depletion in guinea pigs

Malondialdehyde (MDA) and diene conjugates (DC) and vitamin C levels and the activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were determined in the liver and kidney and their mitochondrial fractions of guinea pigs 48 h after the injection of L-buthionine-(S,R)-sulfoximine (BSO), a glutathione (GSH) depleting agent. In BSO-induced GSH depletion, lipid peroxidation and SOD activities were found to be increased but GSH-Px activities did not change in the liver and kidney and their mitochondrial fractions. In addition, vitamin C levels remained unchanged in the liver and kidney homogenates. These results indicate that GSH depletion may influence oxidative stress in the liver and kidney and their mitochondrial fractions of guinea pigs.     

Effects of vitamin E supplementation on oxidative stress in streptozotocin induced diabetic rats: investigation of liver and plasma

This experimental study was designed to investigate the effects of vitamin E supplementation, especially on lipid peroxidation and antioxidant status elements 3/4 namely, glutathione (GSH), CuZn superoxide dismutase (CuZn SOD), and glutathione peroxidase (GSH Px), both in blood and liver tissues of streptozotocin (STZ) diabetic rats. The extent to which blood can be used to reflect the oxidative stress of the liver is also investigated. In diabetic rats, plasma lipid peroxide values were not significantly different,from control,whereas erythrocyte CuZn SOD (p < 0.01), GSH Px (p < 0.001) activities and plasma vitamin E levels (p < 0.001), were significantly more elevated than controls. Vitamin E supplementation caused significant decreases of erythrocyte GSH level (p < 0.01) in control rats and of erythrocyte GSH Px activity (p < 0.05) in diabetic rats. Liver findings revealed significantly higher lipid peroxide (p < 0.001) and vitamin E (p < 0.01) levels and lower GSH (p < 0.001), CuZn SOD (p < 0.001) and GSH Px (p < 0.01) levels in diabetic rats. A decreased hepatic lipid peroxide level (p < 0.01) and increased vitamin E/lipid peroxide ratio (p < 0.001) were observed in vitamin E supplemented, diabetic rats. A vitamin E supplementation level which did not cause any increase in the concentration of the vitamin in the liver or blood, was sufficient to lower lipid peroxidation in the liver. Vitamin E/lipid peroxide ratio is suggested as an appropriate index to evaluate the efficiency of vitamin E activity,independent of tissue lipid values. Further, the antioxidant components GSH, GSH Px and CuZn SOD and the relationships among them, were affected differently in the liver and blood by diabetes or vitamin E supplementation.     

Antioxidant and methyl donor effects of betaine versus ethanol-induced oxidative stress in the rat liver

Oxidative stress is one hypothesis for the association of ethanol consumption with cardiovascular, cerebrovascular, and liver diseases. Thus, we examined whether oral betaine can act as a preventive agent in ethanol-induced oxidative stress on the rat liver. A total of 32 male Sprague–Dawley rats were divided into four equal groups. The control group received normal saline. The ethanol group was administered ethanol (4 g/kg). The betaine group received betaine [1.5 % (w/w) of the total diet], and the betaine plus ethanol group (Bet. & Eth.) were administered with betaine; after 120 min, the rats received ethanol. All of the treatments were applied for 2 months via gavage. Elevation of glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were observed in the betaine-treated groups. Thiobarbituric acid reactive substances (TBARS, an indicator of lipid peroxidation) concentration also decreased in the betaine-treated rats as compared to the ethanol group. There was also a significant reduction in plasma total homocysteine (tHcy) concentration in the betaine and Bet. & Eth. groups as compared to the ethanol-treated rats. In contrast, ethanol treatment in rats resulted in significant lower antioxidant enzyme activities (GPx and SOD), and indicated lipid peroxidation to the liver, as monitored by the elevation in TBARS level. Administration of ethanol to rats also induced toxicity in their liver, as shown by the histopathological findings, whereas betaine could suppress liver damages in the Bet. & Eth. group. Overall, oral pretreatment with betaine significantly prevented ethanol-induced oxidative stress and hyperhomocysteinemia via increasing antioxidant enzyme activities and decreasing tHcy concentration. Thus, betaine may be recommended as a therapeutic agent for patients with liver damages induced by oxidative stress in various diseases.     

Effect of pretreatment with artichoke extract on carbon tetrachloride-induced liver injury and oxidative stress.

Artichoke is a plant with antioxidant properties. In this study, we investigated the effect of artichoke extract pretreatment on carbon tetrachloride (CCl(4))-induced oxidative stress and hepatotoxicity. Rats were given artichoke leaf extract (1.5g/kg/day) by gavage for 2 weeks and after then CCl(4) (1ml/kg; i.p.) was applied. All rats were killed 24h after the CCl(4) injection. CCl(4) administration resulted in hepatic necrosis and significant increases in plasma transaminase activities as well as hepatic malondialdehyde (MDA) and diene conjugate (DC) levels in the liver of rats. Glutathione (GSH) and vitamin C levels decreased, but vitamin E levels increased in the liver of CCl(4)-treated rats. Hepatic superoxide dismutase (SOD) activities remained unchanged, but glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities decreased following CCl(4) treatment. In rats pretreated with artichoke extract, significant decreases in plasma transaminase activities and amelioration in histopathological changes in the liver were observed following CCl(4) treatment as compared to CCl(4)-treated rats. In addition, hepatic MDA and DC levels decreased, but GSH levels and GSH-Px activities increased without any change in other antioxidant parameters following CCl(4) treatment in artichoke-pretreated rats. The present findings indicate that in vivo architoke extract administration may be useful for the prevention of oxidative stress-induced hepatotoxicity.     

Hepatic glutathione mediated antioxidant system in ethanol treated rats: Decline with age.

Alcoholism is a pervasive problem. The aim of the present study was to clarify the effect of ethanol on the hepatic glutathione antioxidant system in young and elderly rats. Male albino Wistar rats of two age groups (3 months and 18 months old) were divided into two experimental groups. The first group of untreated rats served as controls (C; young n=6 and old n=6) and second group received ethanol (Et; young n=6 and old n=6) 2g of ethanol/kg b.w. for 2 months. After the completion of last treatment glutathione (GSH) and antioxidant enzymes glutathione peroxidase (GSH-Px), glutathione reductase (GR) and glutathione-S-transferase (GST) were determined. All these parameters including GST were remarkably decreased in the liver with advancing of age. The ethanol treatment decreased GSH, GSH-Px and GR, whereas, GST was increased in both age groups. The decrease of hepatic antioxidant status with ethanol and aging may be due to over production of free radicals. The changes of parameters studied were greater in the older than in the young rats. In conclusion, ethanol stress exhibited age dependent response on glutathione mediated antioxidant system in the liver.     

Hepatoprotection with a chloroform extract of Launaea procumbens against CCl4-induced injuries in rats

ABSTRACT: BACKGROUND: Launaea procumbens (Asteraceae) is used as a folk medicine to treat hepatic disorders in Pakistan. The effect of a chloroform extract of Launaea procumbens (LPCE) was evaluated against carbon-tetrachloride (CCl4)-induced liver damage in rats. METHODS: To evaluate the hepatoprotective effects of LPCE, 36 male Sprague-Dawley rats were equally divided into six groups. Animals of group 1 (control) had free access to food and water. Group II received 3 ml/kg of CCl4 (30% in olive oil v/v) via the intraperitoneal route twice a week for 4 weeks. Group III received 1 ml of silymarin via gavage (100 mg/kg b.w.) after 48 h of CCl4 treatment whereas groups IV and V were given 1 ml of LPCE (100 and 200 mg/kg b.w., respectively) after 48 h of CCl4 treatment. Group VI received 1 ml of LPCE (200 mg/kg b.w.) twice a week for 4 weeks. The activities of the antioxidant enzymes catalase, peroxidase (POD), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione S-transferase (GST), glutathione reductase (GSR), glutathione (GSH) and lipid peroxidation (thiobarbituric acid reactive substances (TBARS)) were measured in liver homogenates. DNA damage, argyrophilic nucleolar organizer regions (AgNORs) counts and histopathology were studied in liver samples. Serum was analyzed for various biochemical parameters. Phytochemical composition in LPCE was determined through high-performance liquid chromatography (HPLC). RESULTS: LPCE inhibited lipid peroxidation, and reduced the activities of aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase in serum induced by CCl4. GSH contents were increased as were the activities of antioxidant enzymes (catalase, SOD, GST, GSR, GSH-Px) when altered due to CCl4 hepatotoxicity. Similarly, absolute liver weight, relative liver weight and the number of hepatic lesions were reduced with co-administration of LPCE. Phyochemical analyses of LPCE indicated that it contained catechin, kaempferol, rutin, hyperoside and myricetin. CONCLUSION: These results indicated that Launaea procumbens efficiently protected against the hepatotoxicity induced by CCl4 in rats, possibly through the antioxidant effects of flavonoids present in LPCE. KEYWORDS: Launaea procumbens, hepatic injuries, flavonoids, antioxidant enzymes, carbon tetrachloride.     

Protective effects of Picorrhiza kurroa extract against 2-acetylaminofluorene-induced hepatotoxicity in Wistar rats.

Picrorrhiza kurroa has been shown to impart significant hepatoprotective activities, partly by modulation of free radical--induced lipid peroxidation. Lipid peroxidation and reactive oxygen species are associated with hepatic injury. The effect of P. kurroa treatment on the antiproliferative response and, hepatic antioxidant enzymes of rats administered with 2-acetylaminofluorene (2-AAF) was studied in Wistar rats. 2-AAF (50 mg/kg body weight, i.p.) enhances hepatic lipid peroxidation, with reduction in hepatic glutathione content, glutathione peroxidase, glutathione reductase, catalase, and glutathione-s-transferase. There was an increase in the levels of transaminase enzymes and LDH. 2-AAF treatment also enhanced ornithine decarboxylase (ODC) activity and [3H] thymidine incorporation into hepatic DNA. Pretreatment of rats orally with P. kurroa extract (250 and 500 mg/kg body weight) resulted in significant decrease in lipid peroxidation, transaminase enzymes, LDH, hepatic ODC activity, and DNA synthesis (p < 0.001). Hepatic glutathione content (p < 0.001), glutathione metabolizing enzymes (p < 0.001), and antioxidant enzymes were also recovered to significant level (p < 0.001).     

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 CoCl₂ (157 ppm Co²⁺) 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, CoCl₂ 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 CoCl₂ during late pregnancy and early postnatal period affects antioxidant enzyme activities and lipid peroxidation indicating liver damage in mothers and their offspring.     

Effects of administration of the standardized Panax ginseng extract G115 on hepatic antioxidant function after exhaustive exercise.

The effect of prolonged treatment with the standardized Panax ginseng extract G115 on the antioxidant capacity of the liver was investigated. For this purpose, rats that had received G115 orally at different doses for 3 months and untreated control rats were subjected to exhaustive exercise on a treadmill. A bell-shaped dose response on running time was obtained. The results showed that the administration of G115 significantly increases the hepatic glutathione peroxidase activity (GPX) and the reduced glutathione (GSH) levels in the liver, with a dose-dependent reduction of the thiobarbituric acid reactant substances (TBARS). After the exercise, there is reduced hepatic lipid peroxidation, as evidenced by the TBARS levels in both the controls and the treated animals. The GPX (glutathione peroxidase) and SOD (superoxide dismutase) activity are also significantly increased in the groups receiving G115, compared with the controls. The hepatic transaminase levels, ALT (Alanine-amino-transferase) and AST (Aspartate-amino-transferase), in the recuperation phase 48 h after the exercise, indicate a clear hepatoprotective effect related to the administration of the standardized Panax ginseng extract G115. At hepatic level, G115 increases the antioxidant capacity, with a marked reduction of the effects of the oxidative stress induced by the exhaustive exercise.     

Response of liver to lipopolysaccharide treatment in male and female rats

Gender is considered to be an important factor in endotoxin-induced tissue damage. Our aim was to examine the role of sex on the prooxidant–antioxidant status, necrotic and apoptotic events in the liver of lipopolysaccharide (LPS)-treated rats. We determined levels of lipid peroxides, non-enzymatic and enzymatic antioxidants, and expressions of apoptosis-related proteins, antiapoptotic B cell lymphoma-2 (Bcl-2) and proapoptotic Bax, caspase-3 activity and apoptotic cell numbers in the liver. Hepatic histopathology and serum alanine transaminase (ALT) and aspartate transaminase (AST) activities were also investigated. Male and female Wistar rats (180–200 g) were injected with LPS (10 mg/kg, i.p.) and examinations were performed 6 h after the injection. Significant increases in hepatic thiobarbituric acid reactive substances and diene conjugate levels were observed in male and female rats following LPS treatment. However, there were no changes in hepatic glutathione, vitamin E and vitamin C levels together with superoxide dismutase, glutathione peroxidase and glutathione transferase activities. LPS treatment caused significant increases in serum ALT and AST activities and lymphocyte infiltration and necrotic changes in the livers. Bcl-2 and Bax expressions, caspase-3 activity and apoptotic cell numbers were also found to be increased in both groups. In conclusion, no sex-dependent difference was observed in the changed hepatic prooxidant–antioxidant status of rats following LPS treatment. Besides, the process leading to apoptosis and necrosis in the liver showed a similar pattern in both gender of rats.     

Cadmium-induced hepatotoxicity in rats and the protective effect of naringenin

This experiment pertains to the protective role of naringenin against cadmium (Cd)-induced oxidative stress in the liver of rats. Cadmium is a major environmental pollutant and is known for its wide toxic manifestations. Naringenin is a naturally occurring citrus flavonone which has been reported to have a wide range of pharmacological properties. In the present investigation cadmium (5 mg/kg) was administered orally for 4 weeks to induce hepatotoxicity. Liver damage induced by cadmium was clearly shown by the increased activities of serum hepatic marker enzymes namely aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma glutamyl transferase (GGT) and serum total bilirubin (TB) along with the increased level of lipid peroxidation indices (thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides) and protein carbonyl contents in liver. The toxic effect of cadmium was also indicated by significantly decreased levels of enzymatic antioxidants (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST)) and non-enzymatic antioxidants (reduced glutathione (GSH), vitamin C and vitamin E). Administration of naringenin at a dose of (50 mg/kg) significantly reversed the activities of serum hepatic marker enzymes to their near-normal levels when compared to Cd-treated rats. In addition, naringenin significantly reduced lipid peroxidation and restored the levels of antioxidant defense in the liver. The histopathological studies in the liver of rats also showed that naringenin (50 mg/kg) markedly reduced the toxicity of cadmium and preserved the normal histological architecture of the tissue. The present study suggested that naringenin may be beneficial in ameliorating the cadmium-induced oxidative damage in the liver of rats.     

Role of quercetin in preventing thioacetamide-induced liver injury in rats

In hepatic toxicity induced in rats by two injections of thioacetamide (TAA, 350 mg/kg with an interval of 8 hr), the action of quercetin was investigated. After 96 hr, TAA administration resulted in hepatic necrosis, significant increases in serum transaminase activity, and increases in hepatic lipoperoxidation. Thioacetamide-induced hepatotoxicity also showed changes in antioxidant enzymes in the liver of rats, with alterations in p-ERK 1/2 (phosphorylated extracellular-signal related kinase 1/2) as well as an imbalance between proapototic protein Bax and anti-apoptotic protein Bcl-2 expression. With administration of the flavonoid quercetin (50 mg/Kg i.p.) for four consecutive days following TAA, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity were close to normal values in rats. Histological findings suggested that quercetin had a preventive effect on TAA-induced hepatic necrosis. Quercetin treatment caused significant decreases in lipid peroxide levels in the TAA-treated rats, with some changes in antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Quercetin also inhibited the change of the p-ERK1/2 by TAA and significantly prevented the increase in Bax/Bcl-2 ratio, thus preventing apoptosis. Findings indicate that quercetin may have a preventive effect on TAA-induced hepatotoxicity by modulating the oxidative stress parameters and apoptosis pathway.     

Dehydroepiandrosterone improves hepatic antioxidant systems after renal ischemia-reperfusion injury in rabbits

This study evaluated the effects of dehydroepiandrosterone (DHEA) on the oxidant [malondialdehyde (MDA)] and antioxidant [superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and glutathione (GSH)] systems in liver after renal ischemia-reperfusion (IR) injury in rabbits. Thirty rabbits were randomly assigned to 3 groups of 10: group I (sham operation), group II (renal IR group), and group III (DHEA, 25 mg/kg, s.c., 15 min pre-ischemia). Renal IR injury in group II caused a decrease of SOD (25%), GPx (36%), and CAT (26%) activities and GSH levels (32%), and increases of MDA (30%) in liver and of ALT and AST activities in serum, compared to group I. DHEA administration decreased the hepatic MDA level (19%) and serum ALT activity (30%) (p <0.01 and p <0.05, respectively), and considerably increased hepatic GSH levels and GPx activities (p <0.01 for both) in group III, compared to group II. These results suggest that DHEA treatment has beneficial effects on antioxidant defenses against hepatic injury after renal IR in rabbits, possibly by augmenting GSH levels and lowering MDA production.     

Gadolinium chloride suppresses styrene-induced cytochrome P450s expression in rat liver

To assess the effect of gadolinium (Gd) on the expression of several forms of cytochrome P450 (P450s) and antioxidant enzymes, we treated rats with gadolinium chloride (25 mg as Gd/kg body weight) 4 h after styrene (a multiple P450 inducer) treatment (600 mg/kg). Gd treatment significantly suppressed styrene-inducible cytochrome P4502B1 (CYP2B1), CYP2B2, CYP2E1, and CYP3A2 mRNA expressions to 48.6%, 69.8%, 61.1%, and 38.5%, accompanying with the reduction of proteins expression to 1.42%, 31.2%, 21.1% and 21.1%, respectively, compared with styrene alone treatment. Gd suppressed styrene-inducible CYP1A2 expression, but only at the protein level. On the other hand, styrene treatment caused a decrease in reduced form of glutathione (GSH), as well as increases in lipid peroxide and serum ALT and AST activities, suggesting the occurrence of hepatic damage probably due to styrene-induced oxidative stress in rat liver. Post-treatment of Gd attenuated this styrene-caused hepatic damage. Moreover, mRNA expressions of cellular antioxidant enzymes such as catalase, CuZn-superoxide dismutase (CuZnSOD) and glutathione peroxidase (GPX) were hardly changed by styrene and/or Gd treatment. In summary, Gd suppressed styrene-inducible expression of not only CYP2B1 but also several forms of P450 at both the mRNA and protein levels, along with attenuation of styrene-caused liver damage. These findings suggested that Gd is a chemo-preventive agent against hepatic damage caused by xenobiotics requiring biotransformation.     

Effect of binge ethanol treatment on prooxidant-antioxidant balance in rat heart tissue

Binge drinking of alcohol is known to cause cardiac dysfunction in some drinkers. This study was designed to examine the effect of ethanol on rat heart tissue with an experimental model mimicking human binge drinking. Female Sprague-Dawley rats were given ethanol diluted with normal saline (40%, v:v) by gavage at the dose of 5.0g/kg every 12h for 3 doses as total. Serum activities of lactate dehydrogenase (LDH), creatine phosphokinase (CK) and aspartate transaminase (AST) were determined. Endogenous lipid peroxidation was assessed by measuring the levels of malondialdehyde (MDA) in heart homogenates. In vitro susceptibility of tissues to oxidative stress was assessed by using two different media. Tissue glutathione (GSH) and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities were determined. All serum enzymatic activities were found markedly elevated in ethanol group. Binge ethanol administration significantly enhanced endogenous lipid peroxidation and caused an enhanced in vitro susceptibility to lipid peroxidation. Levels of reduced GSH and GSH-Px and GST activities were found unchanged as compared to controls. SOD activity was found significantly increased. As a conclusion, binge ethanol consumption which was applied to rats to investigate acute tissue injury, appeared to confirm the generation of oxidative stress in rat hearts.     

Effect of streptozotocin on glutathione and lipid peroxide levels in various tissues of rats.

In this study, the effect of streptozotocin (STZ) on lipid peroxidation and glutathione (GSH) content was investigated in the liver, pancreas and kidney of rats. Lipid peroxide levels were significantly increased in homogenates and mitochondrial fractions of the liver, kidney and pancreas after STZ administration. GSH levels in hepatic and pancreatic tissues were decreased but unchanged in the kidney of diabetic rats. GSH content in hepatic mitochondrial fraction was also decreased compared to control group. On the other hand, the destruction of pancreatic beta-cells was also observed histopathologically. Our results indicate that oxidative stress may play an important role in STZ induced diabetes and mitochondrial fraction may be the target in this toxicity.     

Chlorella vulgaris extract ameliorates carbon tetrachloride-induced acute hepatic injury in mice

The possible protective effects of Chlorella vulgaris extract (CVE) on carbon tetrachloride (CCl₄)-induced acute hepatic injury in mice and the mechanism underlying these effects was investigated. CCl₄ administration caused a marked increase in the levels of serum aminotransferases, lipid peroxidation and cytochrome P450-2E1 (CYP450) expression. Also, decreased glutathione (GSH) content and activities of cellular antioxidant defense enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase and glutathione-S-transferase (GST) were found after CCl₄ exposure. All of these phenotypes were markedly reversed by preadministration of the mice with CVE. In addition, CVE exhibited antioxidant effects on FeCl₂–ascorbate induced lipid peroxidation in mouse liver homogenates, and on superoxide radical scavenging activity. Taken together, these results suggest that CVE produced a protective action on CCl₄-induced acute hepatic injury in mice, presumably through blocking CYP-mediated CCl₄ bioactivation, inducing the GSH levels, antioxidant enzyme activities and free radical scavenging effect. Therefore, CVE may be an effective hepatoprotective agent and viable candidate for treating hepatic disorders and other oxidative stress-related diseases.     

Antihyperglycemic and antioxidant activities of alcoholic extract of Commiphora mukul gum resin in streptozotocin induced diabetic rats

Background and objectives: The present study investigated the effect of Commiphora mukul ethanol extract gum resin (CMEEt) on streptozotocin (STZ) induced diabetic rats by measuring fasting blood glucose, plasma insulin, plasma lipid profile, atherogenic index, hepatic lipid peroxidation (LPO), protein oxidation (PO) and activities of enzymatic antioxidants. Methods: Wistar albino rats were divided into 4 groups, normal control group, CM-treated control group, diabetic control group and CM-treated diabetic group. For induction of diabetes, STZ was administered at a dose of 55 mg/kg body weight, meanwhile CM-treated groups were administered CMEEt at a dose of 200 mg/kg body weight for 60 days. Body weight, plasma glucose and insulin levels were determined in different experimental days, after end of the experimental period the plasma lipid profile and antioxidant enzymes were determined in hepatic tissue. Results: Increase in plasma glucose, total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), hepatic LPO and PO levels with decrease in plasma high density lipoprotein cholesterol (HDL-C), insulin, hepatic reduced glutathione (GSH) content and activities of antioxidant enzymes namely, glutathione peroxidase (GPX), glutathione reductase (GR), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) were the salient features observed in diabetic rats. On the other hand, oral administration of CMEEt at a dose of 200 mg/kg for 60 days resulted in the prevention of above mentioned abnormalities. Conclusion: The results suggest that CMEEt could be beneficial in the treatment of diabetes, characterized by atherogenous lipoprotein profile, aggravated antioxidant status and impaired glucose metabolism and in their prevention.     

Hepatoprotective effect of the natural fruit juice from Aronia melanocarpa on carbon tetrachloride-induced acute liver damage in rats.

The fruits of Aronia melanocarpa are rich in anthocyanins--plant pigments with anti-inflammatory and antioxidant activity. We studied the effect of the natural fruit juice from A. melanocarpa (NFJAM) on carbon tetrachloride (CCl4)-induced acute liver damage in rats. Histopathological changes such as necrosis, fatty change, ballooning degeneration and inflammatory infiltration of lymphocytes around the central veins occurred in rats following acute exposure to CCl4 (0.2 ml kg(-1), 2 days). The administration of CCl4 increased plasma aspartate transaminase (AST) and alanine transaminase (ALT) activities, induced lipid peroxidation (as measured by malondialdehyde (MDA) content in rat liver and plasma) and caused a depletion of liver reduced glutathione (GSH). NFJAM (5, 10 and 20 ml kg(-1), 4 days) dose-dependently reduced the necrotic changes in rat liver and inhibited the increase of plasma AST and ALT activities, induced by CCl4 (0.2ml kg(-1), 3rd and 4th days). NFJAM also prevented the CCl4-induced elevation of MDA formation and depletion of GSH content in rat liver.