Rahmat Ali Khan

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.

Evaluation of phenolic contents and antioxidant activity of various solvent extracts of Sonchus asper (L.) Hill

BackgroundSonchus asper (SA) is traditionally used for the treatment of various ailments associated with liver, lungs and kidneys. This study was aimed to investigate the therapeutic potential of nonpolar (hexane, SAHE; ethyl acetate, SAEE and chloroform, SACE) and polar (methanol, SAME) crude extracts of the whole plant.MethodsTo achieve these goals, several parameters including free-radical (DPPH•, ABTS•+, H2O2 and •OH) scavenging, iron chelating activity, scavenging of superoxide radicals, total flavonoids and total phenolic content (TPC) were examined.ResultsThe SA extracts presented a remarkable capacity to scavenge all the tested reactive species with IC50 values being found at the μg ⁄ ml level. The SAME was shown to have the highest TPCs while lowest IC50 values for the DPPH•, ABTS•+ radical scavenging capacities and iron chelating scavenging efficiency, moreover, SAME had best activities in scavenging of superoxide radicals and hydrogen peroxide as well as potently scavenged the hydroxyl radicals.ConclusionThese results suggest the potential of S. asper as a medicine against free-radical-associated oxidative damage.

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

BackgroundCarissa 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.Methods30 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.ResultsHepatotoxicity 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.ConclusionThese 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.

Prevention of CCl4-induced nephrotoxicity with Sonchus asper in rat

Sonchus asper (SA) is locally used in renal aliments. The present work investigated the antioxidant effects of S. asper methanolic extract (SAME) against CCl(4)-induced nephrotoxicity in Sprague-Dawley male rats. CCl(4) (3 ml/kg b.w., i.p.; 30% in olive oil) biweekly for 4 weeks induced lipid peroxidation, as reflected by significant increase of TBARS; diminished the renal antioxidant defenses, as revealed by a decrease of the level of GSH, CAT, SOD, GST, GSR, GSH-Px and QR while elevated the level of gamma-GT, H(2)O(2) and nitrite contents. CCl(4) caused histopathological injuries and significantly increased the renal AgNORs count and DNA damage. Telomerase activity in kidney was determined positive with CCl(4) treatment. Creatinine, urobilinogen and urea concentration was increased whereas creatinine clearance was decreased in serum and urine. Level of protein and albumin was increased in urine while reduced in serum. Serum level of nitrite was increased with CCl(4) treatment. Treatment of rats with SAME (100, 200mg/kg b.w.) effectively ameliorated the alterations induced with CCl(4) in lipid peroxidation, antioxidant defenses, biochemical markers, genotoxicity and renal lesions. The present data suggests that SAME protect the kidneys possibly by alleviating the oxidative stress induced with CCl(4) in rat.

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

BackgroundRutin 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 materials24 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.ResultsRutin 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.ConclusionFrom these results, it is suggested that rutin possesses hepatoprotective properties.

Assessment of flavonoids contents and in vitro antioxidant activity of Launaea procumbens

BackgroundLaunaea procumbens (LP) has been used as a food supplement in Pakistan. In this study methanolic crude extract (LPME) of the whole plant and its different fractions; n-hexane (LPHE); ethyl acetate (LPEE) and chloroform (LPCE) were studied for the determination of total flavonoid and phenolics contents along with multifaceted in vitro scavenging assays.ResultsConsiderable amount of flavonoid and phenolics contents were found in all the fractions. Methanol and chloroform fraction exhibited efficient scavenging of DPPH·, ABTS·+, ·OH, superoxide, lipid peroxide and nitric oxide free radicals. Significant correlation was found between DPPH·, ABTS·+, superoxide radical, β-carotene bleaching restraint and phosphomolybdenum assay with total flavonoids and phenolics contents. High performance chromatography (HPLC) of LPME revealed the presence of vitexin, orientin, rutin, hyperoside, catechin and myricetin.ConclusionThese results reveal the presence of bioactive compounds in LPME, which might be contributed towards the various in vitro scavenging.

Evaluation of Launaea procumbens use in renal disorders: A rat model

INTRODUCTION Carbon tetrachloride exerts its toxicity in rat kidneys through oxidative stress. Launaea procumbens is used ethnopharmacologically in renal disorders. Its methanolic, chloroform, ethyl acetate, and n-hexane fractions were evaluated against CCl(4)-induced nephrotoxicity in rat. MATERIALS AND METHODS Among 16 groups, one was given CCl(4) of 3ml/kg body weight (30% in olive oil i.p.) twice a week for 4 weeks. Others were orally fed with extracts (100, 200mg/kg b.w.) or rutin (50mg/kg b.w.) after 48h of CCl(4) or 200mg/kg b.w. of extracts without CCl(4)-treatment twice a week for 4 weeks. RESULTS CCl(4) exposure led to a significant oxidative stress in kidneys which was remarkably attenuated with co-administration of various fractions and rutin thereby increased the level of CAT, POD, SOD, GSH, GSR, GST, GSH-Px, quinone reductase, while reduced the xanthine oxidase, gamma-GT, TBARS, H(2)O(2), nitrite, tissue proteins and DNA fragmentation%. Ameliorated effects of fractions and rutin were also recorded for the function of kidneys and the level of urobilinogen, urea, albumin, creatinine, RBC and WBC in urine were decreased. Serum level of creatinine, urobilinogen, BUN, direct bilirubin, total bilirubin and globulin were decreased while total proteins, albumin and creatinine clearance were increased with fractions and rutin. Protective effects of rutin and fractions were also evident on histopathology by reducing glomerular atrophy, tubular degeneration, congestion of blood capillaries, necrosis of epithelium and edema. Similarly body weight was increased while kidney and relative kidney weight was decreased with co-administration of fractions and rutin. CONCLUSION It is suggested that Launaea procumbens effectively protect kidneys against the CCl(4)-induced oxidative damage in rats, through antioxidant and free radical scavenging effects of flavonoids and saponins present in the fractions.

Protective effect of Sonchus asper extracts against experimentally induced lung injuries in rats: a novel study.

In this study, protective effects of methanol extract (SAME) were evaluated against carbon tetrachloride induced oxidative stress in lungs. Male Sprague-Dawley rats were orally fed with various doses (100, 200 mg/kg body weight) of SAME and (50 mg/kg body weight) of rutin after 48 h of CCl(4) treatment (3 ml/kg body weight, 30% in olive oil) biweekly for 4 weeks. The results showed that administration of extracts and rutin significantly restored lung contents of reduced glutathione and activities of catalase, peroxidase, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase, quinine reductase were reduced while lipid peroxide, hydrogen peroxide, nitrite, DNA fragmentation% and activity of γ-glutamyl transferase, increased by CCl(4), were reversed towards the control levels by the supplement of Sonchus asper extracts and rutin. Lung histopathology showed that S. asper extracts and rutin reduced the incidence of lung lesions induced by CCl(4) in rats. These results suggest that S. asper fractions and rutin could protect lung against the CCl(4)-induced oxidative damage in rats.

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

AbstractBackgroundSonchus 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.MethodsTo 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.ResultsThe 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.ConclusionSAME may protect the liver against CCl4-induced oxidative damage in rats.

Brain antioxidant markers, cognitive performance and acetylcholinesterase activity of rats: efficiency of Sonchus asper

BackgroundSonchus asper (SA) is traditionally used as a folk medicine to treat mental disorders in Pakistan. The aim of this study was to investigate the effect of polyphenolic rich methanolic fraction of SA on cognitive performance, brain antioxidant activities and acetylcholinesterase activity in male rats.Methods30 male Sprague–Dawley rats were equally divided into three groups in this study. Animals of group I (control) received saline (vehicle), group II received SA (50 mg/kg) body weight (b.w.), and group III treated with SA (100 mg/kg b.w.,) orally in dimethyl sulphoxide (DMSO) for 7 days. The effect of SA was checked on rat cognitive performance, brain antioxidatant and acetylcholinesterase activities. Evaluation of learning and memory was assessed by a step-through a passive avoidance test on day 6 after two habituation trials and an initial acquisition trial on day 5. Antioxidant potential was determined by measuring activities of superoxide dismutase (SOD), catalase (CAT), contents of thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) in whole-brain homogenates. Acetylcholinesterase (AChE) activity was determined by the colorimetric method.ResultsResults showed that 100 mg/kg b.w., SA treated rats exhibited a significant improvement in learning and memory (step-through latency time). SA administration reduced lipid peroxidation products and elevated glutathione levels in the SA100-treated group. Furthermore, salt and detergent soluble AChE activity was significantly decreased in both SA-treated groups. Short-term orally supplementation of SA showed significant cognitive enhancement as well as elevated brain antioxidant enzymes and inhibited AChE activity.ConclusionThese findings stress the critical impact of Sonchus asper bioactive components on brain function.