Biomedical subjects

Kanwaljit Chopra

Publications and source records attributed to Kanwaljit Chopra.

At least 37 records · Page 2Linked to original sources

PubMed2005

Resveratrol, a polyphenolic phytoalexin, attenuates diabetic nephropathy in rats.

Diabetic nephropathy is a serious microvascular complication and one of the main causes of end-stage renal disease. Various studies have revealed that increased oxidative stress is a major pathophysiological mechanism which is involved in the etiology of diabetic nephropathy. Resveratrol, a polyphenolic phytoalexin present in red wine, is known to possess potent antioxidant properties and thus we aimed to examine its effect on renal function and oxidative stress in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg) in rats. After 4 weeks of STZ injection, rats were divided into four groups: the control rats, diabetic rats and diabetic rats treated with resveratrol (5 and 10 mg/kg, orally) respectively from week 4 up till week 6. At the termination of the experiments, urine albumin excretion, urine output, serum creatinine, blood urea nitrogen, creatinine and urea clearance were measured. The levels of the renal oxidative stress markers malonaldehyde and glutathione and the antioxidant enzymes superoxide dismutase and catalase were measured in kidney homogenate. STZ-injected rats showed significant increases in blood glucose, polyuria, proteinuria and a decrease in body weight compared with age-matched control rats. After 6 weeks, diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine and urea clearance, and proteinuria along with a marked increase in oxidative stress, as determined by lipid peroxidation and activities of key antioxidant enzymes. Treatment with resveratrol significantly attenuated renal dysfunction and oxidative stress in diabetic rats. The present study reinforces the important role of oxidative stress in diabetic kidney and points towards the possible antioxidative mechanism being responsible for the renoprotective action of resveratrol.

Animals↗

PubMed2005

Curcumin, a diferuloylmethane, attenuates cyclosporine-induced renal dysfunction and oxidative stress in rat kidneys.

BACKGROUND: In India, Curcumin (CMN) is popularly known as "Haldi", and has been well studied due to its economic importance. Traditional Indian medicine claims the use of its powder against biliary disorders, anorexia, coryza, cough, diabetic wounds, hepatic disorder, rheumatism and sinusitis. This study was designed to examine the possible beneficial effect of CMN in preventing the acute renal failure and related oxidative stress caused by chronic administration of cyclosporine (CsA) in rats. CMN was administered concurrently with CsA (20 mg/kg/day s.c) for 21 days. Oxidative stress in kidney tissue homogenates was estimated using thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) content, superoxide dismutase (SOD), and Catalase (CAT). Nitrite levels were estimated in serum and tissue homogenates. RESULTS: CsA administration for 21 days produced elevated levels of TBARS and marked depletion of renal endogenous antioxidant enzymes and deteriorated the renal function as assessed by increased serum creatinine, Blood Urea Nitrogen (BUN) and decreased creatinine and urea clearance as compared to vehicle treated rats. CMN markedly reduced elevated levels of TBARS, significantly attenuated renal dysfunction increased the levels of antioxidant enzymes in CsA treated rats and normalized the altered renal morphology. CONCLUSION: In conclusion our study showed that CMN through its antioxidant activity effectively salvaged CsA nephrotoxicity.

Animals↗

PubMed2005

Resveratrol, a polyphenolic phytoalexin protects against cyclosporine-induced nephrotoxicity through nitric oxide dependent mechanism.

Cyclosporine A (CsA) is a potent and effective immunosuppressive agent, but its use is frequently accompanied by severe renal toxicity. The causes for the nephrotoxicity of CsA have not been fully elucidated. Intrarenal vasoconstriction induced by several different mediators, both in humans and experimental animals have been proposed. The present study was designed to investigate the possible protective effect of resveratrol on CsA-induced nephrotoxicity and to explore the possible mechanism involved in resveratrol's effect. Eight groups of rats were employed in this study, group 1 served as control, group 2 rats were treated with olive oil (vehicle for CsA), group 3 rats were treated with CsA (20 mg/kg, s.c. for 21 days), groups 4, 5 and 6 received CsA along with resveratrol (2, 5 and 10 mg/kg, p.o. 24 h before and 21 days concurrently), respectively, group 7 rats were treated with NOS inhibitor, L-NAME (10 mg/kg) along with resveratrol and CsA and group 8 rats received L-NAME along with CsA. CsA administration for 21 days resulted in a marked renal oxidative stress, significantly deranged the renal functions, reduced the tissue and urine nitrite levels and markedly altered the renal morphology. Treatment with resveratrol (5 and 10 mg/kg) significantly improved the renal dysfunction; tissue and urine total nitric oxide levels, renal oxidative stress and prevented the alterations in renal morphology. Concurrent administration of L-NAME blocked the protective effect of resveratrol indicating that resveratrol exerts its protective effect by releasing nitric oxide. These results clearly demonstrate the pivotal role of nitric oxide in etiology of CsA nephrotoxicity and indicate the renoprotective potential of resveratrol in CsA nephrotoxicity.

Animals↗

PubMed2005

Cyclosporine protects against ischemia/reperfusion injury in rat kidneys.

Renal ischemia followed by reperfusion leads to acute renal failure in both native kidneys and renal allografts. Cyclosporine A (CsA) has been used as an immunosuppressive agent in organ transplantation. In the present study, the effect of CsA on ischemia/reperfusion (I/R)-induced injury in the kidney was investigated. Ischemia/reperfusion injury caused a significant deterioration in the renal function, morphology and gave rise to a severe oxidative stress in the kidney. At 3 mg/kg i.v., CsA significantly improved the functional and histological parameters and attenuated the oxidative stress induced by renal ischemia/reperfusion. From the results of our study, it can be concluded that low-dose CsA pretreatment preconditions the rat kidneys against subsequent ischemia/reperfusion injury.

Animals↗

PubMed2005

Effect of molsidomine and L-arginine in cyclosporine nephrotoxicity: role of nitric oxide.

Cyclosporine A (CsA) is a potent and effective immunosuppressive agent, but its action is frequently accompanied by severe renal toxicity. To determine if the renal alterations are mediated directly by cyclosporine or by secondary homodynamic alterations induced by cyclosporine, we evaluated if L-arginine and a nitric oxide donor, molsidomine could prevent these alterations. Eight groups of rats were employed in this study, group 1 served as control, group 2 rats were treated with CsA (20 mg/kg, s.c. for 21 days), group 3 received CsA along with L-arginine (125 mg/kg in drinking water concurrently with CsA), groups 4 and 5 received CsA along with molsidomine (5 and 10 mg/kg, p.o. 24 h before and 21 days concurrently with CsA), group 6 received CsA along with L-arginine (125 mg/l in drinking water concurrently with CsA) and L-NAME (10 mg/kg), groups 7 and 8 received L-NAME (10 mg/kg) along with CsA and molsidomine (5 and 10 mg/kg), respectively. Renal function was assessed by measuring serum creatinine, blood urea nitrogen, creatinine and urea clearance. Tissue and urine nitrite and nitrate levels were measured to estimate the total nitric oxide levels. The renal oxidative stress was measured by renal malondialdehyde levels, reduced glutathione levels and by enzymatic activity of catalase and superoxide dismutase. Renal morphological alterations were assessed by histopathological examination. CsA administration for 21 days resulted in a marked renal oxidative stress, significantly deranged the renal functions as well as renal morphology. Treatment with L-arginine as well as with molsidomine significantly improved the renal dysfunction; tissue and urine total nitric oxide levels, renal oxidative stress and prevented the alterations in renal morphology. This protection against CsA nephrotoxicity was attenuated by treatment with L-NAME, clearly indicating that NO plays a pivotal role in renoprotective effect of L-arginine and molsidomine against cyclosporine nephrotoxicity.

Administration, Oral↗

PubMed2005

Molsidomine, a nitric oxide donor and L-arginine protects against rhabdomyolysis-induced myoglobinuric acute renal failure.

Rhabdomyolysis-induced myoglobinuric acute renal failure accounts for about 10-40% of all cases of acute renal failure (ARF). Nitric oxide and reactive oxygen intermediates play a crucial role in the pathogenesis of myoglobinuric acute renal failure (ARF). This study was designed to investigate the effect of molsidomine and L-arginine in glycerol induced ARF in rats. Six groups of rats were employed in this study, group I served as control, group II was given 50% glycerol (8 ml/kg, intramuscularly), groups III and IV were given glycerol plus molsidomine (5 mg/kg, and 10 mg/kg p.o. route respectively) 60 min prior to the glycerol injection, group V animals were given glycerol plus L-arginine (125 mg/kg, p.o.) 60 min prior to the glycerol injection, and group VI received L-NAME (10 mg/kg, i.p.) along with glycerol 30 min prior to glycerol administration. Renal injury was assessed by measuring plasma creatinine, blood urea nitrogen, creatinine and urea clearance. The oxidative stress was measured by renal malondialdehyde levels, reduced glutathione levels and by enzymatic activity of catalase, reduced glutathione and superoxide dismutase. Tissue and urine nitrite levels were measured as an index of total nitric oxide levels. Glycerol treatment resulted in a marked decrease in tissue and urine nitric oxide levels, renal oxidative stress and significantly deranged the renal functions along with deterioration of renal morphology. Pre-treatment of animals with molsidomine (10 mg/kg) and L-arginine 60 min prior to glycerol injection markedly attenuated fall in nitric oxide levels, renal dysfunction, morphological alterations, reduced elevated TBARS and restored the depleted renal antioxidant enzymes. The animals treated with L-NAME along with glycerol further worsened the renal damage observed with glycerol. As a result, our results indicate that molsidomine and L-arginine may have beneficial effects in myoglobinuric ARF.

Acute Kidney Injury↗

PubMed2005

Hesperidin, a citrus bioflavonoid, decreases the oxidative stress produced by carbon tetrachloride in rat liver and kidney.

BACKGROUND: CCl4 is a well-established hepatotoxin inducing liver injury by producing free radicals. Exposure to CCl4 also induces acute and chronic renal injuries. The present study was designed to establish the protective effect of hesperidin (HDN), a citrus bioflavonoid, on CCl4-induced oxidative stress and resultant dysfunction of rat liver and kidney. METHODS: Animals were pretreated with HDN (100 and 200 mg/kg orally) for one week and then challenged with CCl4 (2 ml/kg/s.c.) in olive oil. Rats were sacrificed by carotid bleeding under ether anesthesia. Liver enzymes, urea and creatinine were estimated in serum. Oxidative stress in liver and kidney tissue was estimated using Thiobarbituric acid reactive substances (TBARS), glutathione (GSH) content, superoxide dismutase(SOD), and Catalase (CAT) RESULTS: CCl4 caused a marked rise in serum levels of ALT and AST (P < 0.05). TBARS levels were significantly increased whereas GSH, SOD and CAT levels decreased in the liver and kidney homogenates of CCl4 treated rats. HDN (200 mg/kg) successfully attenuated these effects of CCl4 CONCLUSION: In conclusion, our study demonstrated a protective effect of HDN in CCl4 induced oxidative stress in rat liver and kidney. This protective effect of HDN can be correlated to its direct antioxidant effect.

Animals↗

PubMed2005

Reversal of LPS-induced central and peripheral hyperalgesia by green tea extract.

Tea has recently attracted a great deal of attention for its beneficial health effects. Green tea polyphenols inhibit the production of arachidonic acid metabolites and leukotrienes resulting in decreased inflammatory responses. In the present study, the effect of green tea extract (GTE) on lipopolysaccharide (LPS)-induced thermal and behavioural hyperalgesia in mice and the possible involvement of the cyclooxygenase pathway in this paradigm was evaluated. GTE (25 mg/kg, i.p.), nimesulide (2 mg/kg, i.p.) and rofecoxib (2 mg/kg, i.p.) significantly attenuated LPS-induced thermal and behavioural hyperalgesia but per se did not modify any of the behavioural effects. Concurrent administration of a subeffective dose of GTE (10 mg/kg, i.p.) and rofecoxib (2 mg/kg, i.p.) or nimesulide (2 mg/kg, i.p.) significantly potentiated the antinociceptive effect of GTE in both LPS-induced thermal and behavioural hyperalgesia with nimesulide showing a more pronounced enhancing effect. Thus it can be concluded that GTE attenuates LPS-induced central and peripheral hyperalgesia by selective inhibition of cyclooxygenase-2 enzyme.

Analgesics, Non-Narcotic↗

PubMed2005

Renal protective effect of molsidomine and L-arginine in ischemia-reperfusion induced injury in rats.

BACKGROUND: Nitric oxide (NO), synthesized from L-arginine by the enzyme NO synthase (NOS) seems to play an ambiguous role during tissue ischemia-reperfusion (I/R) injury. This study was designed to investigate the effects of molsidomine, a NO donor and L-arginine in I/R induced renal failure in rats METHODS: The protective effect of molsidomine and L-arginine against the damage inflicted by I/R was investigated in Sprague-Dawley rats. In one set of experiments animals were unilaterally nephrectomized, and subjected to 45 min of left renal pedicle occlusion and in another set both the renal pedicles were occluded for 45 min followed by 24 h of reperfusion. Molsidomine (10 mg/kg, p.o.) was administered twice, 30 min before ischemia and 12 h after the reperfusion period, while L-arginine was administered once, 30 min before ischemia. At the end of the reperfusion period, rats were sacrificed. Tissue and urine nitrite levels were measured to assess the total NO levels. Thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) levels, catalase (CAT), and superoxide dismutase (SOD) activities were determined in renal tissue. Serum creatinine and BUN concentrations were measured for the evaluation of renal function. RESULTS: Ischemic control animals demonstrated severe deterioration of renal function, renal morphology, reduced levels of tissue, and urine NO levels and a significant renal oxidative stress. Pretreatment of animals with molsidomine and L-arginine markedly attenuated renal dysfunction, morphological alterations, improved the tissue as well as urine NO contents, reduced elevated TBAR levels and restored the depleted renal antioxidant enzymes. CONCLUSIONS: The findings imply that NO play a causal role in I/R induced renal injury.

Animals↗

PubMed2005

Role of nitric oxide in resveratrol-induced renal protective effects of ischemic preconditioning.

BACKGROUND: Resveratrol, a natural antioxidant and polyphenol found in red wine and grapes, has been found to pharmacologically precondition the heart through upregulation of nitric oxide (NO). This study was designed to explore the involvement of NO in the renoprotective effect of resveratrol in renal ischemic preconditioning in rat kidney. METHODS: Ischemic preconditioning was induced by three cycles 2-minutes of ischemia followed by 5 minutes of reperfusion before 45 minutes of prolonged ischemia. Resveratrol was given 1 hour before the surgical procedures. RESULTS: Ischemic preconditioning and resveratrol treatment significantly improved the renal dysfunction, decrease in total NO levels, and oxidative stress induced by 45 minutes of ischemia followed by 24 hours of reperfusion. Histopatholgic examination of the kidneys of ischemic/reperfusion rats revealed severe renal damage, which was attenuated in both preconditioned and resveratrol-treated animals. Preconditioning and resveratrol administration led to a marked increase in NO levels in kidney. Renoprotective effects of resveratrol were abolished when animals were pretreated with NG-nitro-L-arginine methyl ester, a nonspecific NO synthase inhibitor. CONCLUSIONS: These findings demonstrate an important contributory role of NO in the protection afforded by resveratrol in renal ischemic preconditioning. CLINICAL RELEVANCE: It is now well established that brief periods of ischemia followed by reperfusion render a variety of tissues tolerant to subsequent ischemia/reperfusion-induced injury. This phenomenon, referred to as ischemic preconditioning, was first demonstrated in the dog myocardium. The potential for clinical application of such a powerful protective phenomenon has generated enormous interest in identifying the underlying intracellular signaling pathways, with the ultimate aim of pharmacologically exploiting these mechanisms to develop therapeutic strategies that can enhance tolerance to ischemia/reperfusion injury in patients. This study explored the possible involvement of nitric oxide in renal ischemic preconditioning.

Angiogenesis Inhibitors↗

PubMed2005

Modulatory role of green tea extract on antinociceptive effect of morphine in diabetic mice.

Diabetic neuropathic pain is an important microvascular complication, and morphine has been demonstrated to be ineffective in this condition. Therefore the present study was designed to investigate the modulatory effect of green tea extract (GTE) on the decreased antinociceptive effect of morphine in diabetic mice. The tail withdrawal test was performed for measurement of the nociceptive threshold in both streptozotocin (STZ)-injected and control mice. Four weeks after administration of STZ, antinociception of morphine (5 mg/kg, s.c.) alone or in combination with GTE (25, 50, and 100 mg/kg, i.p.) was measured. Experimental diabetes markedly decreased the antinociceptive effect of morphine. The decrement in morphine response was significantly attenuated by GTE administration. When GTE (25 mg/kg) and a nitric oxide (NO) inhibitor, L-N(G)-nitroarginine methyl ester (L-NAME) (10 mg/kg, i.p), were co-administered along with morphine (5 mg/kg, s.c) in diabetic mice, the antinociceptive action of morphine was significantly increased as compared with the GTE + morphine-treated diabetic group, but the increased antinociceptive action was significantly attenuated by administration of an NO precursor, L-arginine (100 mg/kg, i.p), instead of L-NAME. Plasma nitrite concentrations were estimated using the Griess reagent. Diabetes significantly increased the plasma nitrite levels that were attenuated by GTE administration. When GTE (25 mg/kg) and L-NAME (10 mg/kg, i.p) were co-administered along with morphine (5 mg/kg, s.c) in diabetic mice, the plasma nitrite levels were significantly decreased as compared with the GTE + morphine alone-treated diabetic group, but the decreased plasma nitrite levels were significantly reversed by administration of L-arginine (100 mg/kg) instead of L-NAME. It may be concluded that increased NO formation may be responsible for the decreased antinociceptive effect of morphine in diabetic mice and that GTE restored the antinociceptive effect of morphine by inhibition of NO production. The results of the present study indicate the possibility of adding GTE as an adjuvant in the treatment of diabetic neuropathic pain.

Analgesics↗

PubMed2005

Green tea extract and catechin ameliorate chronic fatigue-induced oxidative stress in mice.

Chronic fatigue syndrome (CFS) is an illness characterized by persistent and relapsing fatigue, often accompanied by numerous symptoms involving various body systems. The etiology of CFS remains unclear, but a number of studies have shown that oxidative stress may be involved in its pathogenesis. The present study was designed to investigate the protective effect of green tea extract (GTE) and catechin in the mouse model of CFS. Animals were subjected to a forced swimming test session of 6 minutes every day for 7 days; a significant increase in immobility time on successive days represented the CFS in mice. Biochemical analysis revealed that the chronic swim test significantly increased lipid peroxidation levels and decreased glutathione levels in mouse whole-brain homogenate. Treatment with GTE (25 or 50 mg/kg, i.p.) and catechin (50 or 100 mg/kg, i.p.) for 7 days reversed the increase in immobility time. Protection was correlated with the lowered levels of lipid peroxidation and restoration of reduced glutathione levels in the brains of fatigued mice. These findings strongly suggest the pivotal role of oxidative stress in the pathophysiology of CFS and that GTE and catechin could be used as potential agents in the management of CFS and warrant the inclusion of GTE and catechin in the treatment regimen of CFS patients.

Animals↗

PubMed2005

Participation of alpha2 receptors in the antinociceptive activity of quercetin.

The present work was planned to evaluate the antinociceptive activity of quercetin, its site of action, and the involvement of adrenergic receptors in mediating the antinociceptive activity in thermal and chemonociceptive assays. Eight groups were employed in this study: Groups I, II, and III received quercetin alone in different doses, group IV animals were administered clonidine, group V animals were co-administered quercetin and clonidine, group VI animals were administered yohimbine 30 minutes prior to administratin of quercetin, group VII animals were administered yohimbine 30 minutes prior to co-administration of quercetin and clonidine, and group VIII animals were administered 0.5% carboxymethylcellulose in saline (vehicle for quercetin). The thermal nociception was measured by tail flick and hot plate methods. Quercetin produced a significant analgesic effect in a dose-dependent manner. Co-administration of low doses of quercetin and clonidine produced a synergistic analgesic effect. Pretreatment with yohimbine significantly reversed quercetin-as well as clonidine/quercetin combination-induced effects. The results of this study reveal that quercetin induces an antinociceptive effect and that this effect involves primarily the modulation of adrenergic pathways.

Adrenergic alpha-Agonists↗

PubMed2005

Antimutagenic and antioxidant/prooxidant activity of quercetin.

The present study has been performed to evaluate the antimutagenic activity of quercetin, ascorbic acid and their combination against an oxidative mutagen. An effort was also made to correlate this activity to the in vitro antioxidant activity of these agents. Antimutagenicity testing was done in Ames Salmonella Assay system using Salmonella typhimurium TA102 against t-butylhydroperoxide as an oxidative mutagen. In vitro antioxidant scavenging activity was tested for DPPH free radical, superoxide anion, hydrogen peroxide and hydroxyl radical in their specific test systems. Quercetin (0.5-8 nmole/plate) and ascorbic acid (0.1-100 micromole/plate) showed significant effect. Quercetin (4 and 8 nmole/plate) when combined with ascorbic acid (500 nmole/plate) showed an increase in the antimutagenic activity. In vitro antioxidant activity of quercetin was better than ascorbic acid in all the test systems used. The study indicated that the antimutagenic activity of quercetin was not solely accountable by its antioxidant nature. However, in vitro free radical scavenging activity of quercetin correlated well with the antimutagenic activity.

Antimutagenic Agents↗

PubMed2005

Diltiazem attenuates oxidative stress in diabetic rats.

Diabetic nephropathy is the main cause of end stage renal damage. Oxidative stress is involved in the etiology of diabetic nephropathy and intracellular calcium is reported to play a considerable role in the development of renal damage in the diabetic kidney. Calcium antagonism can slow the progression of renal impairment in diabetes. The present study was thus designed to examine the effect of a nondihydropyridine calcium channel blocker, diltiazem, on renal function, oxidative stress, and nitric oxide (NO) release in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg) in rats. After 4 weeks of STZ injection, the rats were divided in to four groups: control rats, diabetic rats treated with saline, and two groups of diabetic rats treated with diltiazem (5 and 10 mg/kg, i.p, respectively) for 8 weeks starting from 4 weeks after STZ injection. Renal function was assessed by creatinine, blood urea nitrogen, creatinine clearance, and urea clearance. Oxidative stress was measured by renal malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), and catalase. We also measured renal nitrite levels. At the end of the 8 weeks, diabetic rats exhibited renal dysfunction as evidenced by reduced creatinine and urea clearance along with enhanced albumin excretion rate as compared with control rats. Biochemical analysis of kidneys revealed a marked increase in oxidative stress demonstrated by increased lipid peroxidation and decreased activities of key antioxidant enzymes, GSH, SOD, and catalase in diabetic rats. Release of NO also significantly higher in diabetic rats than controls. Chronic treatment with diltiazem in diabetic rats significantly attenuated both renal dysfunction and oxidative stress along with increased NO levels as compared with untreated diabetic rats. The kidneys of diabetic rats showed morphological changes such as hyaline casts, glomerular thickening, and moderate interstitial fibrosis and arteriolopathy, whereas diltiazem administration markedly prevented diabetic-induced renal morphological alterations. The present study suggests that oxidative stress/nitrosative stress is increased in the diabetic kidney and calcium channel blockage can prevent these changes. The results also suggest that in STZ-induced diabetic rats, the protective action of diltiazem might be mediated, at least in part, by its effect on tissue oxidant/antioxidant status.

Animals↗

PubMed2004

Delineation of antimutagenic activity of catechin, epicatechin and green tea extract.

Tea is consumed worldwide as second largest to water in popularity as a beverage. It has been reported that tea extracts have antibacterial, antiviral, antioxidative, antitumor and antimutagenic activities. The protective effect of green tea has been assumed to be due to the powerful scavenging and antioxidative property of high concentrations of unpolymerised catechins and their gallates. In the present proposal green tea extract (GT), (+)-catechin (C) and (-)-epicatechin (EC) were investigated for their antioxidant activity by different in vitro methods like (i) DPPH assay (ii) superoxide anion scavenging and (iii) hydrogen peroxide scavenging activity. Further these agents were also tested against mutagenesis using the well-standardized Ames microsomal test system. The Ames tester strain Salmonella typhimurium TA102, which readily responds to reactive oxygen species, was used and the antimutagenic activity was evaluated against oxidative mutagens tertiary butyl hydroperoxide (ID50-24.41, 29.63 and 113.23 microg for EC, C and GT, respectively) and hydrogen peroxide (ID50-17.3, 18.4 and 88.1 microg for EC, C and GT, respectively). Ascorbic acid was used as a standard antioxidant in all the experiments. Results indicate that all the three agents possess excellent DPPH free radical scavenging activity (IC50-1.5 microg for EC, 3.45 microg for C and 3.8 microg for GT), good hydrogen peroxide (IC50-11.18 microg for EC, 13.5 microg for C and 11.78 microg for GT) and superoxide anion scavenging (IC50-1.64 microg for EC, 1.74 microg for C and 3.52 microg for GT) activities. Further, they also show antimutagenic activity in the above-mentioned test systems establishing their antioxidant nature to be responsible for such activity. The in vitro antioxidant activity correlates well with the antimutagenic action. (-)-Epicatechin is indicated to be a better agent in comparison to the other two agents (ID50-1.2 times more than C and 5 times more than GT in antimutagenicity studies against t-BOOH and hydrogen peroxide induced mutagenesis). Ascorbic acid however showed a much less activity (ID50-12.1 mg against t-BOOH and 7.2 mg with hydrogen peroxide induced mutagenesis).

Antimutagenic Agents↗

PubMed2004

Reversal of experimental myoglobinuric acute renal failure in rats by quercetin, a bioflavonoid.

The occurrence of acute renal failure (ARF) following rhabdomyolysis has been put at between 10 and 40% of cases, and accounts for between 3 and 15% of all cases of ARF. Reactive oxygen intermediates have been demonstrated to play an etiological role in myoglobinuric renal failure. This study was performed to explore the protective effect of quercetin, a bioflavonoid, in an experimental model of myoglobinuric ARF in rats. Four groups of rats were employed in this study: group 1 served as control, group 2 was given 50% glycerol (8 ml/kg, i.m.), group 3 was given glycerol + quercetin (2 mg/kg, i.p.), and group 4 was given glycerol + DMSO (the solvent for quercetin, 5 ml/kg, i.p.). Renal injury was assessed by measuring serum creatinine, blood urea nitrogen, creatinine and urea clearance. The oxidative stress was measured by renal malondialdehyde levels, reduced glutathione levels and by enzymatic activity of catalase, glutathione reductase, and superoxide dismutase. Glycerol administration resulted in a marked renal oxidative stress, significantly deranged the renal functions as well as renal cytoarchitecture. All these factors were significantly improved by quercetin treatment. Because of its radical-scavenging and iron-chelating properties, quercetin protected the kidney against the glycerol-induced oxidative stress and resultant renal dysfunction. Based on these results, this study confirms the role of oxidative stress and demonstrates the renoprotective potential of quercetin in this rhabdomyolysis-mimicking model.

Acute Kidney Injury↗

PubMed2004

Effect of irbesartan on the antioxidant defence system and nitric oxide release in diabetic rat kidney.

BACKGROUND/AIMS: Increased oxidative stress is involved in the aetiology of diabetic nephropathy, and angiotensin II is reported to play a considerable role in the development of renal damage in diabetic kidney. Angiotensin antagonism can slow the progression of renal impairment in diabetes. The present study was thus designed to examine the effect of an angiotensin II type 1 (AT1) receptor antagonist, irbesartan on renal function, oxidative stress and nitric oxide (NO) release in streptozotocin (STZ)-induced diabetic rats. METHODS: Diabetes was induced by a single intraperitoneal injection of streptozotocin (65 mg/kg) in rats. After 4 weeks of STZ injection, rats were divided into four groups: the control rats, diabetic rats and diabetic rats treated with irbesartan (25 and 50 mg/kg, orally) respectively till 8 weeks starting from 4 weeks after STZ injection. Renal function was assessed by creatinine, blood urea nitrogen, creatinine clearance and urea clearance. Oxidative stress was measured by renal malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase. We also measured renal nitrite levels. RESULTS: At the end of the 8th week, diabetic rats exhibited renal dysfunction as evidenced by reduced creatinine and urea clearance along with enhanced albumin excretion rate as compared with control rats. Biochemical analysis of kidneys revealed a marked increase in oxidative stress demonstrated by increased lipid peroxidation and decreased activities of key antioxidant enzymes, GSH, SOD and catalase in diabetic rats. NO release was also significantly higher in diabetic rats than controls. Chronic treatment with irbesartan in diabetic rats significantly attenuated both renal dysfunction and oxidative stress along with increased NO levels as compared with untreated diabetic rats. The kidneys of diabetic rats showed morphological changes such as hyaline casts, glomerular thickening and moderate interstitial fibrosis and arteriolopathy, whereas irbesartan administration markedly prevented diabetic-induced renal morphological alterations. CONCLUSIONS: The present study suggests that oxidative stress/nitrosative stress is increased in the diabetic kidney and AT1 receptor blockade can prevent these changes. The results also suggest that in STZ-induced diabetic rats, the protective action of irbesartan might be mediated, at least in part, by its effect on tissue oxidant/antioxidant status.

Angiotensin II Type 1 Receptor Blockers↗