Biomedical subjects

Kanwaljit Chopra

Publications and source records attributed to Kanwaljit Chopra.

63 records · Page 4Linked to original sources

PubMed2003

Attenuation of cyclosporine-induced renal dysfunction by catechin: possible antioxidant mechanism.

One of great use of immunosuppressant, Cyclosporine-A (CsA) is in the solid organ transplantation; however the extensive use of this is cautionable due to its toxic effect in renal tissue, characterized by the tubular atrophy, interstitial fibrosis, and progressive renal impairment. However, there are many mediators are associated with pathogenesis of nephrotoxicity of CsA, the exact mechanism is still in debate. Recent studies indicate that Reactive Oxygen Species (ROS) induced oxidative stress and lipid peroxidations are the important mechanisms implicated in the pathophysiology of nephrotoxicity with CsA. In the present study we examined effect of dietary flavonoid catechin on oxidative damage in cyclosporine-A induced nephrotoxicity. Chronic administration of CsA (20 mg/kg/day) subcutaneously for 21 days significantly decreased the body weight as compared with vehicle treated rats. CsA (20 mg/kg/day) administration for 21 days significantly decreased the renal function by increase in the serum creatinine, blood urea nitrogen, and decrease in the creatinine and urea clearance as compared with vehicle treated rats. Catechin (100 mg/kg/day) for 21 days along with CsA significantly reversed the changed renal parameters, however lower dose of catechin (50 mg/kg/day) restored only increased serum creatinine levels as compared with CsA alone treated group. Biochemical analysis revealed that chronic administration of CsA (20 mg/kg/day) for 21 days significantly induced lipid peroxidation and decreased the glutathione levels in the kidney homogenate of rats. It is also observed that chronic CsA administered rats showed decrease in antioxidant defense enzyme superoxide dismutase and increase in the catalase activity as compared with vehicle treated rats. Co-administration of catechin (100 mg/kg/day) orally along with CsA for 21 days significantly reduced the lipid peroxidation and restored the decreased glutathione levels as compared with CsA alone group, but lower dose of catechin (50 mg/kg/day) restored only decreased glutathione levels induced by CsA. Co-administration of only higher dose of catechin (100 mg/kg/day) along with CsA significantly increased the superoxide dismutase (SOD) levels as compared with CsA alone treated group. It is also observed that catechin (100 mg/kg/day) along with CsA further increased the catalase levels as compared with CsA alone treated group, but not with lower dose of catechin. Animals administered with catechin (100 mg/kg/day) alone for 21 days showed significant increase in the catalase levels as compared with vehicle treated group. The major findings of the present study suggest that oxidative stress might play a significant role in CsA-induced nephrotoxicity. In conclusion, dietary administration of flavonoid catechin could be a useful component for the prevention/treatment of CsA-induced nephrotoxicity.

Animals↗

PubMed2003

Antidepressant activity of quercetin, a bioflavonoid, in streptozotocin-induced diabetic mice.

Depression is highly prevalent in diabetics and is associated with poor glucose regulation and increased risk of diabetic complications. Identification and effective treatment of comorbid depression are increasingly being considered essential components of clinical care of diabetics. In the present study, the antidepressant activity of quercetin (50 and 100 mg/kg, i.p.), a bioflavonoid, was evaluated using the Porsolt forced swimming-induced behavioral despair test in control and 6-week-streptozotocin-induced diabetic mice. The effect of quercetin was compared with that of the classical antidepressants fluoxetine (5 mg/kg, i.p.) and imipramine (15 mg/kg, i.p.). Streptozotocin-induced diabetic mice exhibited prolonged immobility duration during the test as compared with age-matched control mice. Quercetin dose-dependently reduced the immobility period in diabetic mice, and this effect was comparable to that of fluoxetine (5 mg/kg, i.p.) and imipramine (15 mg/kg, i.p.). Fluoxetine and imipramine significantly lowered the immobility time in naive mice also, but quercetin failed to induce any antidepressant activity in naive mice. The results of our preliminary study indicate that quercetin has the potential to be employed as a therapy for depression associated with diabetes.

Animals↗

PubMed2003

Attenuation of glycerol-induced acute renal failure in rats by trimetazidine and deferoxamine.

The pathogenesis of glycerol-induced myoglobinuric acute renal failure involves, among other causes, ischaemia, vascular congestion, and reactive oxygen metabolites. The aim of this study was to investigate the roles of ischaemia and iron-induced oxidative stress by employing trimetazidine, an anti-ischemic drug with an additional antioxidant effect, and deferoxamine, an iron chelator, in glycerol-induced acute renal failure in rats. Five groups of rats were employed in this study: group 1 served as control group, group 2 was given 50% glycerol alone (8 ml/kg i.m.), group 3 was given glycerol plus trimetazidine (3 mg/kg), and groups 4 and 5 were given glycerol plus deferoxamine (50 and 100 mg/kg, respectively). Renal injury was assessed by measuring plasma creatinine and blood urea nitrogen levels and creatinine and urea clearances. The oxidative stress was measured on the basis of the renal malondialdehyde and reduced glutathione levels and the activities of catalase, glutathione reductase, and superoxide dismutase. Glycerol treatment resulted in marked renal oxidative stress and deranged renal functions which significantly improved by trimetazidine and deferoxamine treatments. Deferoxamine, by interacting with Fenton reaction chemistry, and trimetazidine, by its anti-ischaemic and antioxidative properties, protected the kidney against the oxidative stress and the resultant renal dysfunction produced by glycerol. Based on these results, this study points towards renal ischaemia and iron as potential mediators and demonstrates the potential beneficial effects of deferoxamine and trimetazidine in glycerol-induced acute renal failure in rats.

Acute Kidney Injury↗

PubMed2002

Selective angiotensin II type 1 receptor blockade ameliorates cyclosporine nephrotoxicity.

Nephrotoxicity associated with cyclosporine A (CsA) administration is characterized by marked renal vasoconstriction, interstitial fibrosis and arteriolar hypertrophy. The molecular mechanisms of CsA nephrotoxicity are not well characterized, but previous studies have demonstrated that angiotensin II (Ang II), the primary mediator of renin-angiotensin system (RAS) cascade plays a role in its pathogenesis. Recent studies also suggest an involvement of reactive oxygen species (ROS) in CsA nephrotoxicity. There is emerging evidence that Ang II induces oxidative stress in vitro and in vivo. The aims of this study were to investigate the role of Ang II-induced oxidative stress in CsA nephrotoxicity, and to examine the effects of the insurmountable Ang II type 1 (AT (1)) receptor antagonist, candesartan on CsA-induced nephrotoxicity in rats. Candesartan cilexetil (1.0 mg kg (-1), perorally (p.o.), once a day) was administered 24 h before and 21 days concurrently with CsA (20 mg kg(-1), subcutaneously (s.c.)). Tissue lipid peroxidation was measured as thiobarbituric acid reacting substances (TBARS). Renal function was assessed by estimating serum creatinine, blood urea nitrogen (BUN), creatinine and urea clearance. Renal morphological alterations were assessed by histopathological examination of Haematoxylin-Eosin, PAS and Mason's trichome stained sections of the kidneys. CsA (20 mg kg (-1), s.c.) administration for 21 days produced elevated levels of TBARS and deteriorated the renal function as assessed by increased serum creatinine, BUN and decreased creatinine and urea clearance as compared to vehicle treated rats. The kidneys of CsA-treated rats showed severe striped interstitial fibrosis, arteriolopathy, glomerular basement thickening, tubular vacuolisation and hyaline casts. Candesartan cilexetil (1.0 mg kg (-1)) markedly reduced elevated levels of TBARS, significantly attenuated renal dysfunction and morphological changes in CsA-treated rats. These results clearly demonstrate the pivotal role of Ang II-induced oxidative stress and the therapeutic potential of AT (1)receptor antagonists in ameliorating CsA-induced nephrotoxicity.

Angiotensin Receptor Antagonists↗

PubMed2002

Probiotics: potential pharmaceutical applications.

Realisation of the importance of human gut microbiota in health restoration and maintenance has kindled an interest in probiotics. Probiotics are defined as the microbial food supplements, which beneficially affect the host by improving its intestinal microbial balance. Probiotics are the health enhancing functional food ingredients used therapeutically to prevent diarrhea, improve lactose tolerance and modulate immunity. They may also have potential to prevent cancer and lower serum cholesterol levels. Lactobacillus, Bifidobacterium and several other microbial species are perceived to exert such effects by changing the composition of the gut microbiota. However, it is important that exogenously administered bacteria reach and establish themselves in the large intestine in an intact form. The use of non-digestible oligosaccharides ('prebiotics') can fortify intestinal microflora and stimulate their growth. The present review encompasses information regarding the probiotics and their proposed uses. It addresses the concepts of prebiotics and synbiotics, the application of genetic engineering to produce newer probiotics. Finally, the list of commercially available products are reviewed with discussion of questions regarding the reliability, utility and the safety of these products.

Animals↗

PubMed2002

Oxidative stress-mediated renal dysfunction by cyclosporine A in rats: attenuation by trimetazidine.

Cyclosporine A (CsA) is one of the first line immunosuppressants employed in the management of solid organ transplantation and autoimmune diseases. The clinical utility of CsA is limited by the frequent occurrence of chronic nephrotoxicity, characterized by tubular atrophy, interstitial fibrosis and progressive renal impairment. The pathogenesis of CsA nephrotoxicity is still not well delineated. Recent evidences suggest that reactive oxygen species (ROS) play an important role in CsA nephrotoxicity. The present study was designed to demonstrate the role of oxidative stress, its relation to renal dysfunction and to investigate the effect of trimetazidine (TMZ), an anti-ischemic agent with free radical scavenging property, in CsA-induced nephrotoxicity. TMZ (2.5 mg/kg, p.o., twice a day) was administered 24 h before and 21 days concurrently with CsA (20 mg/kg, s.c.). Tissue lipid peroxidation was measured as thiobarbituric acid reacting substances (TBARS). Renal function was assessed by measuring the plasma and urine creatinine concentrations, blood and urine urea nitrogen levels and the creatinine and urea clearances. Renal morphological alterations were assessed by histopathological examination of Hematoxylin-Eosin, PAS and Masson's trichome stained sections of the kidneys. CsA (20 mg/kg, s.c) administration for 21 days produced elevated levels of TBARS and decreased renal function as assessed by increased plasma creatinine, BUN and decreased creatinine and urea clearances as compared to vehicle treated rats. The kidneys of CsA treated rats showed severe striped interstitial fibrosis, arteriolopathy, glomerular basement thickening, tubular vacuolization and hyaline casts. TMZ (2.5 mg/kg) markedly reduced elevated levels of TBARS, significantly attenuated renal dysfunction and the morphological changes in CsA treated rats. These results clearly demonstrate the pivotal role of reactive oxygen species and their relation to renal dysfunction and point to the therapeutic potential of an anti-ischemic agent, trimetazidine, in CsA-induced nephrotoxicity.

Animals↗

PubMed2002

Salvage of cyclosporine A-induced oxidative stress and renal dysfunction by carvedilol.

BACKGROUND: Cyclosporine A (CsA) is the first-line immunosuppressant employed for the management of solid organ transplantation and autoimmune diseases. Nephrotoxicity is the major limitation of CsA use. Recent evidence suggests that reactive oxygen species (ROS) play an important role in mediating CsA nephrotoxicity. The present study was designed to investigate effects of carvedilol, a third-generation beta-blocker with potent free radical-scavenging activity on CsA-induced oxidative stress and resultant renal dysfunction in a rat model of chronic CsA nephrotoxicity. METHODS: Carvedilol (2.0 and 4.0 mg/kg i.p.) and propranolol (10 mg/kg i.p.) were administered to separate group of animals 24 h before and concurrently with CsA (20 mg/kg s.c.) for 21 days. Renal function was assessed by estimating plasma creatinine, blood urea nitrogen (BUN), creatinine and urea clearance. Tissue lipid peroxidation was measured as thiobarbituric acid-reacting substances (TBARS). Renal morphological alterations were assessed by histopathological examination of hematoxylin-eosin, PAS and Masson's trichrome stained sections of the kidneys. RESULTS: CsA (20 mg/kg s.c) administration for 21 days produced elevated levels of TBARS and deteriorated renal function as assessed by increased plasma creatinine, BUN and decreased creatinine and urea clearance as compared to vehicle-treated rats. The kidneys of CsA-treated rats showed severe striped interstitial fibrosis, arteriolopathy, glomerular basement thickening, tubular vacuolization and hyaline casts. Propranolol neither decreased TBARS nor improved the renal dysfunction and morphological changes induced by CsA. Both doses of carvedilol markedly reduced elevated levels of TBARS, whereas the higher dose of carvedilol significantly attenuated renal dysfunction and morphological changes in CsA-treated rats. CONCLUSIONS: These data clearly indicate the renoprotective potential of carvedilol in CsA-induced nephrotoxicity and suggest a significant contribution of its antilipoperoxidative property in this beneficial effect.

Animals↗

PubMedDate not supplied

The effect of quercetin, a bioflavonoid on ischemia/reperfusion induced renal injury in rats.

There is increasing evidence to suggest that toxic oxygen radicals play a role in the pathogenesis of ischemia/reperfusion (I/R) injury in the kidney. This study was designed to investigate the effects of quercetin (Qr), a bioflavonoid in ischemia-reperfusion induced renal failure in rats. The effect of quercetin against the damage inflicted by reactive oxygen species (ROS) during renal I/R was investigated in Sprague-Dawley rats using histopathological and biochemical parameters. In one set of experiments, animals were unilaterally nephrectomized and subjected to 45 min of left renal pedicle occlusion, and in another set both renal pedicles were occluded for 45 min followed by 24 h of reperfusion. Quercetin (2 mg/kg, 30 mg/kg, i.p. and 100 mg/kg, p.o.) was administered 2 h prior to ischemia. At the end of the reperfusion period, rats were sacrificed. Thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) levels, glutathione reductase (GR), catalase (CAT), and superoxide dismutase (SOD) activities were determined in renal tissue. Serum creatinine and blood urea nitrogen (BUN) concentrations were measured for the evaluation of renal function. Ischemic control animals demonstrated severe deterioration of renal function, renal morphology and a significant renal oxidative stress. Pretreatment of animals with quercetin (2 mg/kg and 30 mg/kg, i.p.) markedly attenuated renal dysfunction, morphological alterations, reduced elevated TBARS levels and restored the depleted renal antioxidant enzymes, whereas the (100 mg/kg, p.o.) dose of quercetin failed to revert the renal I/R induced changes. The findings imply that ROS play a causal role in I/R induced renal injury and quercetin exerts protective and deleterious effects in the kidney, depending upon the dose.

Animals↗

PubMedDate not supplied

Protective effect of catechin on ischemia-reperfusion-induced renal injury in rats.

There is increasing evidence to suggest that toxic oxygen radicals play a role in the pathogenesis of ischemia/reperfusion (I/R) injury in the kidney. This study was designed to investigate the effects of catechin, a bioflavonoid, in I/R-induced renal failure in rats. The protective effect of catechin against the damage inflicted by reactive oxygen species (ROS) during renal I/R was investigated in Sprague Dawley rats using histopathological and biochemical parameters. 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. Catechin (40 mg/kg, po) was administered twice daily for 4 days and 2 h prior to ischemia. At the end of the reperfusion period, rats were sacrificed. Thiobarbituric acid reactive substances (TBARS), reduced glutathione levels, glutathione reductase, catalase, and superoxide dismutase activities were determined in renal tissue. Serum creatinine and blood urea nitrogen concentrations were measured for the evaluation of renal function. Ischemic control animals demonstrated severe deterioration of renal function, renal morphology and a significant renal oxidative stress. Pretreatment of animals with catechin markedly attenuated renal dysfunction, morphological alterations, reduced elevated TBARS levels and restored the depleted renal antioxidant enzymes. The findings imply that ROS play a causal role in I/R-induced renal injury, and catechin exerts renoprotective effects probably by the radical scavenging and antioxidant activities.

Animals↗