Phytochemical screening and protective effects of Trifolium alexandrinum (L.) against free radical-induced stress in rats.

Trifolium alexandrinum is traditionally used in various human ailments, including renal dysfunctions. The present experiment was designed to investigate antioxidant and nephroprotective effect of T. alexandrinum methanolic extract (TAME) against CCl4-induced oxidative stress in albino rats. Results of in vitro study revealed significant (P < 0.05) antioxidant effects. The ameliorative role of TAME was also examined by investigating the level of antioxidant enzymes catalase (CAT), peroxidase (POD), glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST), nonenzymatic antioxidant viz; reduced glutathione contents (GSH) and lipid peroxidation products (TBARS) in the renal tissue homogenate in CCl4-treated rats. The intraperitoneal injection of 1 mL/kg b.w. CCl4 caused a significant depletion in the activity antioxidant enzymes and increased the TBARS contents. Supplementation of TAME at 200 mg/kg b.w. for 2 weeks significantly improved activities of antioxidant enzymes and reduced TBARS formation. Co-treatment of TAME also presented significant protection in maintaining renal urine and serum markers. Antioxidant and nephroprotective effects of TAME are associated with its polyphenolic constituents.

CCl4-induced hepatotoxicity: protective effect of rutin on p53, CYP2E1 and the antioxidative status in rat.

BACKGROUND: Rutin is a polyphenolic natural flavonoid which possesses antioxidant and anticancer activity. In the present study the hepatoprotective effect of rutin was evaluated against carbon tetrachloride (CCl4)-induced liver injuries in rats. METHODS AND MATERIALS: 24 Sprague-Dawley male rats were equally divided into 4 groups for the assessment of hepatoprotective potential of rutin. Rats of group I (control) received only vehicles; 1 ml/kg bw of saline (0.85%) and olive oil (3 ml/kg) and had free access to food and water. Rats of group II, III and IV were treated with CCl4 (30% in olive oil, 3 ml/kg bw) via the intraperitoneal route twice a week for four weeks. The rutin at the doses of 50 and 70 mg/kg were administered intragastrically after 48 h of CCl4 treatment to group III and IV, respectively. Protective effect of rutin on serum enzyme level, lipid profile, activities of antioxidant enzymes and molecular markers were calculated in CCl4-induced hepatotoxicity in rat. RESULTS: Rutin showed significant protection with the depletion of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (γ-GT) in serum as was raised by the induction of CCl4. Concentration of serum triglycerides, total cholesterol and low density lipoproteins was increased while high-density lipoprotein was decreased with rutin in a dose dependent manner. Activity level of endogenous liver antioxidant enzymes; catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSHpx), glutathione-S-transferase (GST) and glutathione reductase (GSR) and glutathione (GSH) contents were increased while lipid peroxidation (TBARS) was decreased dose dependently with rutin. Moreover, increase in DNA fragmentation and oxo8dG damages while decrease in p53 and CYP 2E1 expression induced with CCl4 was restored with the treatment of rutin. CONCLUSION: From these results, it is suggested that rutin possesses hepatoprotective properties.

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

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.

Hepatoprotective activity of Sonchus asper against carbon tetrachloride-induced injuries in male rats: a randomized controlled trial.

BACKGROUND: Sonchus asper (SAME) is used as a folk medicine in hepatic disorders. In this study, the hepatoprotective effects of the methanol extract of SAME was evaluated against carbon tetrachloride (CCl4)-induced liver injuries in rats. METHODS: To evaluate the hepatoprotective effects of SAME, 36 male Sprague-Dawley rats were equally divided into 6 groups. Rats of Group I (control) were given free access to approved feed and water. Rats of Group II were injected intraperitoneally with CCl4 (3 ml/kg) as a 30% solution in olive oil (v/v) twice a week for 4 weeks. Animals of Groups III (100 mg/kg) and IV (200 mg/kg) received SAME, whereas those of Group V were given silymarin via gavage (100 mg/kg) after 48 h of CCl4 treatment. Group VI received SAME (200 mg/kg) twice a week for 4 weeks without CCl4 treatment. Various parameters, such as the serum enzyme levels, serum biochemical marker levels, antioxidant enzyme activities, and liver histopathology were used to estimate the hepatoprotective efficacy of SAME. RESULTS: The administration of SAME and silymarin significantly lowered the CCl4-induced serum levels of hepatic marker enzymes (aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase), cholesterol, low-density lipoprotein, and triglycerides while elevating high-density lipoprotein levels. The hepatic contents of glutathione and activities of catalase, superoxide dismutase, glutathione peroxidase, glutathione S-transferase, and glutathione reductase were reduced. The levels of thiobarbituric acid-reactive substances that were increased by CCl4 were brought back to control levels by the administration of SAME and silymarin. Liver histopathology showed that SAME reduced the incidence of hepatic lesions induced by CCl4 in rats. CONCLUSION: SAME may protect the liver against CCl4-induced oxidative damage in rats.

Hepatoprotective effects of methanol extract of Carissa opaca leaves on CCl4-induced damage in rat.

BACKGROUND: Carissa opaca (Apocynaceae) leaves possess antioxidant activity and hepatoprotective effects, and so may provide a possible therapeutic alternative in hepatic disorders. The effect produced by methanolic extract of Carissa opaca leaves (MCL) was investigated on CCl4-induced liver damages in rat. METHODS: 30 rats were divided into five groups of six animals of each, having free access to food and water ad libitum. Group I (control) was given olive oil and DMSO, while group II, III and IV were injected intraperitoneally with CCl4 (0.5 ml/kg) as a 20% (v/v) solution in olive oil twice a week for 8 weeks. Animals of group II received only CCl4. Rats of group III were given MCL intragastrically at a dose of 200 mg/kg bw while that of group IV received silymarin at a dose of 50 mg/kg bw twice a week for 8 weeks. However, animals of group V received MCL only at a dose of 200 mg/kg bw twice a week for 8 weeks. The activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and γ-glutamyltransferase (γ-GT) were determined in serum. Catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione peroxidase (GSH-Px), glutathione reductase (GSR) and quinone reductase (QR) activity was measured in liver homogenates. Lipid peroxidation (thiobarbituric acid reactive substances; TBARS), glutathione (GSH) and hydrogen peroxide (H2O2) concentration was also assessed in liver homogenates. Phytochemicals in MCL were determined through qualitative and high performance liquid chromatography (HPLC) analysis. RESULTS: Hepatotoxicity induced with CCl4 was evidenced by significant increase in lipid peroxidation (TBARS) and H2O2 level, serum activities of AST, ALT, ALP, LDH and γ-GT. Level of GSH determined in liver was significantly reduced, as were the activities of antioxidant enzymes; CAT, POD, SOD, GSH-Px, GSR, GST and QR. On cirrhotic animals treated with CCl4, histological studies showed centrilobular necrosis and infiltration of lymphocytes. MCL (200 mg/kg bw) and silymarin (50 mg/kg bw) co-treatment prevented all the changes observed with CCl4-treated rats. The phytochemical analysis of MCL indicated the presence of flavonoids, tannins, alkaloids, phlobatannins, terpenoids, coumarins, anthraquinones, and cardiac glycosides. Isoquercetin, hyperoside, vitexin, myricetin and kaempherol was determined in MCL. CONCLUSION: These results indicate that MCL has a significant protective effect against CCl4 induced hepatotoxicity in rat, which may be due to its antioxidant and membrane stabilizing properties.

Carbon tetrachloride-induced nephrotoxicity in rats: protective role of Digera muricata.

Digera muricata is used in renal disorders in folk medicine. Generation of reactive radicals has been implicated in carbon tetrachloride-induced nephrotoxicity, which are involved in lipid peroxidation, accumulation of dysfunctional proteins, leading to injuries in kidneys. The present study was aimed to evaluate the efficacy of Digera muricata on the kidney function in CCl(4)-induced injuries. CCl(4) treatment (5 ml/kg body wt., i.p. CCl(4):olive oil; 1:9) significantly increased the level of urine creatinine, protein, nitrite, urobilinogen, red blood cells (RBCs), leucocytes count, and levels of blood urea nitrogen (BUN). Level of proteins and DNA fragmentation %, argyrophilic nucleolar organizer regions (AgNORs) count in renal tissues was also significantly increased. Activity of antioxidant enzymes; catalase, peroxidase, superoxide dismutase and reduced glutathione (GSH) were decreased while thiobarbituric acid reactive substances (TBARSs) were increased with CCl(4) treatment. DNA ladder assay was intimately related with the DNA fragmentation assay. Telomerase activity was determined in the CCl(4)-treated renal tissue homogenate. Treatment with n-hexane (HDMP) and methanolic (MDMP) extracts of Digera muricata (200 and 250 mg/kg body wt., oral, respectively) effectively attenuated the alterations in the biochemical markers, telomerase activity was inhibited and confirms the restoration of normalcy and accredits the protective role of Digera muricata against CCl(4)-induced nephrotoxicity.