Biomedical subjects

Kanwaljit Chopra

Publications and source records attributed to Kanwaljit Chopra.

At least 55 records · Page 3Linked to original sources

PubMed2004

Protective effect of naringin, a bioflavonoid on ferric nitrilotriacetate-induced oxidative renal damage in rat kidney.

An iron chelate, ferric nitrilotriacetate (Fe-NTA), induces acute proximal tubular necrosis as a consequence of lipid peroxidation and oxidative tissue damage that eventually leads to high incidence of renal adenocarcinomas in rodents. This study was designed to investigate the effect of Naringin, a bioflavonoid with anti-oxidant potential, on Fe-NTA-induced nephrotoxicity in rats. One hour after a single intra-peritoneal (i.p.) injection of Fe-NTA (8 mg iron/kg body weight), a marked deterioration of renal architecture and renal function was observed. Fe-NTA induced a significant renal oxidative stress, demonstrated by elevated thiobarbituric acid reacting substances (TBARS) and reduction in activities of renal catalase, superoxide dismutase, and glutathione reductase. Pre-treatment of animals with Naringin, 60 min before Fe-NTA administration, markedly attenuated renal dysfunction, morphological alterations, reduced elevated TBARS, and restored the depleted renal anti-oxidant enzymes. These results clearly demonstrate the role of oxidative stress and its relation to renal dysfunction and suggest a protective effect of Naringin on Fe-NTA-induced nephrotoxicity in rats.

Animals↗

PubMed2004

Protective effect of naringin, a bioflavonoid on glycerol-induced acute renal failure in rat kidney.

Rhabdomyolysis-induced myoglobinuric acute renal failure accounts for about 10-40% of all cases of acute renal failure (ARF). Reactive oxygen intermediates have been demonstrated to play an etiological role in myoglobinuric renal failure. This study was designed to investigate the effect of naringin, a bioflavonoid with antioxidant potential, in glycerol-induced ARF in rats. Five groups of rats were employed in this study, group I served as control, group II was given 50% glycerol (8 ml/kg, intramuscularly), group III, IV, and V were given glycerol plus naringin 100, 200, and 400mg/kg p.o. route, respectively) 60 min prior to the glycerol injection. 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, glutathione reductase, and superoxide dismutase. Glycerol treatment resulted in a marked renal oxidative stress and significantly deranged the renal functions. Pretreatment of animals with naringin 60 min prior to glycerol injection markedly attenuated renal dysfunction, morphological alterations, reduced elevated thiobarbituric acid reacting substances (TBARS), and restored the depleted renal antioxidant enzymes. These results clearly demonstrate the role of oxidative stress and its relation to renal dysfunction, and suggest a protective effect of naringin in glycerol-induced renal failure in rats.

Acute Kidney Injury↗

PubMed2004

Fluoxetine attenuates thermal hyperalgesia through 5-HT1/2 receptors in streptozotocin-induced diabetic mice.

Diabetic neuropathic pain, an important microvascular complication in diabetes mellitus, is recognised as one of the most difficult types of pain to treat. A lack of understanding of its aetiology, inadequate relief, development of tolerance and potential toxicity of classical antinociceptives warrant the investigation of newer agents to relieve this pain. The aim of the present study was to explore the antinociceptive effect and possible mechanism of action of a serotonin reuptake inhibitor, fluoxetine, in streptozotocin-induced diabetic mice. Four weeks after a single intraperitoneal injection of streptozotocin (200 mg/kg), mice were tested in the tail-immersion and hot-plate assays. Diabetic mice exhibited significant hyperalgesia compared with control mice. Fluoxetine (10 and 20, but not 5 mg/kg, i.p.) injected into diabetic mice produced an antinociceptive effect in both the tail-immersion and hot-plate assays. The percentage maximum possible effect (% MPE) produced by fluoxetine (20 mg/kg, i.p.) was significantly lower in diabetic mice than in control mice. The antinociceptive effect of fluoxetine (20 mg/kg) in diabetic mice was dose-dependently potentiated by pindolol (5 and 10 mg/kg, i.p., a selective 5-HT(1A/1B) receptor antagonist), attenuated by ritanserin (1 and 2 mg/kg, i.p., a selective 5-HT(2A/2C) receptor antagonist) and remained unaffected by ondansetron (1 and 2 mg/kg, i.p., a selective 5-HT(3) receptor antagonist) in both test systems. These results suggest that fluoxetine-induced antinociception primarily involves serotonin pathway modulation through 5-HT(1) and 5-HT(2) receptors, but not through 5-HT(3) receptors, in the chronic pain associated with streptozotocin-induced diabetic neuropathy. Further, the potentiation of the antinociceptive effect of fluoxetine by pindolol indicates the usefulness of a combination of an antidepressant and a 5-HT(1A/1B) receptor antagonist in the treatment of diabetic neuropathic pain in humans.

Analgesics↗

PubMed2004

Reversal of LPS-induced immobility in mice by green tea polyphenols: possible COX-2 mechanism.

An endotoxin (lipopolysaccharide, LPS) is known to activate the hypothalamo-pituitary adrenocortical axis, as well as norepinephrine and indolamine metabolism. Systemically administered LPS produces depression in the forced swimming-induced despair behaviour model in mice. The present study was designed to investigate the effect of green tea extract (GTE) on LPS-induced despair behaviour and to explore the mechanism involved in modulation of LPS-induced immobility by GTE. GTE (10-100 mg/kg) pretreatment reversed LPS-induced immobility in a dose-dependent manner. Rofecoxib (2 mg/kg) and nimesulide (2 mg/kg), COX-2 inhibitors, also reversed the LPS-induced immobility, which was significantly potentiated by concomitant administration of GTE. On the other hand, GTE did not show any potentiating effect on immobility with naproxen (10 mg/kg), which is a nonselective COX blocker. Interestingly the antioxidant, carvedilol (2 mg/kg) did not produce any effect on immobility either in normal or in LPS treated mice. The results of the study implicate the role of COX-2 inhibition by GTE in the reversal of LPS-induced immobility.

Animals↗

PubMed2004

The effect of naringin, 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 naringin (Ng), a bioflavonoid in I/R induced renal failure in rats. The protective effect of naringin 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 24h of reperfusion. Naringin (400 mg kg(-1), p.o.) was administered 60 min prior to ischemia. At the end of the reperfusion period, rats were sacrificed. Thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) levels, 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 naringin 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 naringin exert renoprotective effects probably by the radical scavenging and antioxidant activities.

Administration, Oral↗

PubMed2004

Effect of trimetazidine on renal ischemia/reperfusion 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 trimetazidine, in I/R induced renal failure in rats. The protective effect of trimetazidine (Tmz) 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. Trimetazidine (3 mg kg(-1), i.p.) was administered 30 min prior to ischemia and repeated 12 h after the first dose. 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 trimetazidine 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 trimetazidine exert renoprotective effects probably by the radical scavenging and antioxidant activities.

Animals↗

PubMed2004

Quercetin, a bioflavonoid, attenuates ferric nitrilotriacetate-induced oxidative renal injury in rats.

An iron chelate, ferric nitrilotriacetate (Fe-NTA), induces acute proximal tubular necrosis as a consequence of lipid peroxidation and oxidative tissue damage, that eventually leads to high incidence of renal adenocarcinomas in rodents. This study was designed to investigate the effect of quercetin, a bioflavonoid with antioxidant potential, on Fe-NTA-induced nephrotoxicity in rats. One hour after a single intraperitoneal (i.p.) injection of Fe-NTA (8 mg iron/kg), a marked deterioration of renal architecture and renal function was observed. Fe-NTA induced a significant renal oxidative stress demonstrated by elevated thiobarbituric acid reacting substances (TBARS) and reduction in activities of renal catalase, superoxide dismutase and glutathione reductase. Pretreatment of animals with quercetin (2 mg/kg, i.p.) 30 minutes before Fe-NTA administration markedly attenuated renal dysfunction, morphological alterations, reduced elevated TBARS and restored the depleted renal antioxidant enzymes. These results clearly demonstrate the role of oxidative stress and its relation to renal dysfunction, and suggest a protective effect of quercetin on Fe-NTA-induced nephrotoxicity in rats.

Animals↗

PubMed2004

Amelioration of cyclosporine nephrotoxicity by irbesartan, A selective AT1 receptor antagonist.

Cyclosporine A (CsA), a fungal undecapeptide, is the most common immunosuppressive drug used in organ transplantation and autoimmune diseases. However, nephrotoxicity is the major adverse effect of CsA use. The molecular mechanisms of CsA nephrotoxicity are not well characterized, but more recent studies suggest an involvement of angiotensin II (ANG II) and reactive oxygen species in the development of cyclosporine nephrotoxicity. Induction of heat shock proteins (HSPs) is one of the best-described cellular responses to heat stress, hypoxia, and exposure to oxidants. HSPs have beneficial roles in protein processing and protection against cell injury. There is emerging evidence that ANG II induces oxidative stress in vitro and in vivo. This study was thus designed to investigate the role of Angiotensin II type I (AT1) receptor antagonist, irbesartan, on CsA-induced nephrotoxicity. Five groups of rats were employed in this study: group 1 served as control, group 2 rats were treated with CsA (20 mg kg(-1), subcutaneously for 21 days), and groups 3, 4, and 5 received CsA along with irbesartan (10, 25, and 50 mg kg(-1), perorally 24 hr before and 21 days concurrently), respectively. Renal function was assessed by measuring serum creatinine, blood urea nitrogen, creatinine, and urea clearance. The renal oxidative stress was measured by renal malondialdehyde levels, reduced glutathione levels, and enzymatic activity of catalase, glutathione reductase, and superoxide dismutase. Renal morphological alterations were assessed by histopathological examination. CsA administration for 21 days resulted in a marked renal oxidative stress and significantly deranged the renal functions as well as renal morphology. All these factors were significantly improved by irbesartan (50 mg kg(-1)) treatment. HSP72, HSP47, and HSP25 were clearly induced and expressed in CsA-treated animals. The induction and expression of HSP25 was markedly protected by treatment with irbesartan, whereas the induction and expression of HSP47 and HSP72 remained unaltered with the irbesartan treatment. These results clearly demonstrate the pivotal role of ANG II-induced oxidative stress and therapeutic potential of AT, receptor antagonist in ameliorating CsA-induced nephrotoxicity.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2004

Quercetin, an anti-oxidant bioflavonoid, attenuates diabetic nephropathy in rats.

1. Diabetic nephropathy is an important microvascular complication and one of the main causes of end-stage renal disease. Many in vivo and in vitro studies have indicated that oxidative stress is one of the major pathophysiological mechanisms involved in the development of diabetic nephropathy. In the present study, we examined the effect of an anti-oxidant bioflavonoid quercetin on renal function and oxidative stress in streptozotocin (STZ)-induced diabetic rats. 2. Diabetes was induced in Sprague-Dawley rats with a single intravenous injection of STZ (45 mg/kg). Four weeks after STZ injection, quercetin (10 mg/kg per day) was given orally for 4 weeks in both control and diabetic rats. Plasma glucose levels and bodyweights were measured at 4 and 8 weeks after the STZ injection. At the termination of the experiments, urine albumin excretion, urine output, serum creatinine, blood urea nitrogen, creatinine and urea clearance were measured. The renal oxidative stress marker malonaldehyde, glutathione levels and the anti-oxidant enzymes superoxide dismutase and catalase were measured in kidney homogenate. 3. Streptozotocin-injected rats showed significant increases in blood glucose, polyuria, proteinuria and a decrease in bodyweight compared with age-matched control rats. After 8 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 anti-oxidant enzymes. Treatment with quercetin significantly attenuated renal dysfunction and oxidative stress in diabetic rats. 4. These results confirm the role of oxidative stress in the development of diabetic nephropathy and point to the possible anti-oxidative mechanism being responsible for the nephroprotective action of quercetin.

Animals↗

PubMed2004

Carvedilol attenuates ischemia-reperfusion-induced oxidative 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 carvedilol (CVD), an antihypertensive drug in I/R-induced renal failure in rats. The protective effect of CVD 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. Carvedilol (2 mg/kg, i.p.) was administered twice, 30 min prior to ischemia and 12 h after the reperfusion period. At the end of the reperfusion period, rats were killed. Thiobarbituric acid-reactive substances (TBARS), reduced glutathione (GSH) levels, 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 CVD 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 CVD exerts renoprotective effects probably by the radical scavenging and antioxidant activities.

Animals↗

PubMed2004

Nordihydroguairetic acid, a lignin, prevents oxidative stress and the development of diabetic nephropathy in rats.

Recent evidences indicate a pivotal role of reactive oxygen species in etiology of diabetic nephropathy, an important microvascular complication of diabetes mellitus. Moreover, oxidative stress leads to an increased production of lipoxygenase derivatives which also play a role in diabetic nephropathy. The present study was thus designed to examine the effect of an antioxidant and a lipoxygenase inhibitor, nordihydroguairetic acid (NDGA), on renal function and oxidative stress in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of streptozotocin (65 mg/kg) in rats. After the 4th week of STZ injection, NDGA (5 and 10 mg/kg) was given subcutaneously (s.c.) for another 4 weeks to both control and diabetic rats. 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, glutathione (GSH), superoxide dismutase (SOD) and catalase in diabetic rats. Chronic treatment with NDGA in diabetic rats significantly prevented both renal dysfunction and oxidative stress as compared with vehicle-treated diabetic rats. The kidneys of diabetic rats showed morphological changes such as hyaline casts, glomerular thickening and moderate interstitial fibrosis and arteriolopathy, whereas NDGA administration in diabetic rats markedly prevented renal morphological alterations. These results emphasize the role of oxidative stress in the pathophysiology of diabetic nephropathy and point towards the potential of NDGA as a complementary therapy for the prevention/treatment of diabetic nephropathy.

Animals↗

PubMed2004

Nephrotoxicity and its prevention by catechin in ferric nitrilotriacetate promoted oxidative stress in rats.

Intraperitoneal injection of ferric nitrilotriacetate (Fe-NTA) to rats and mice results in iron-induced free radical injury and cancer in kidneys. This study was designed to investigate the effect of catechin, a bioflavonoid with antioxidant potential, on Fe-NTA-induced nephrotoxicity in rats. Four groups were employed in the present study. Group I served as control group, Group II animals received Fe-NTA (8 mg iron/kg body weight i.p.), Group III animals were given 40 mg/kg catechin p.o. twice a day for 4 days and on the 5th day Fe-NTA was challenged, and Group IV animals received catechin alone for 4 days. Renal function was assessed by measuring plasma creatinine and blood urea nitrogen. The oxidative stress was measured by renal malondialdehyde levels, reduced glutathione levels and by enzymatic activity of catalase, glutathione reductase and superoxide dismutase. One hour after a single intraperitoneal (i.p.) injection of Fe-NTA (8 mg iron/kg), a marked deterioration of renal architecture, renal function and severe oxidative stress was observed. Pretreatment of animals with catechin markedly attenuated renal dysfunction, reduced elevated thiobarbituric acid reacting substances (TBARS), restored the depleted renal antioxidant enzymes and normalized the renal morphological alterations. These results clearly demonstrate the role of oxidative stress and its relation to renal dysfunction, and suggest a protective effect of catechin on Fe-NTA-induced nephrotoxicity in rats.

Animals↗

PubMed2004

Quercetin attenuates thermal hyperalgesia and cold allodynia in STZ-induced diabetic rats.

Neuropathic pain is one of the important microvascular complications of diabetes. Oxidative stress and superoxide play a critical role in the development of neurovascular complications in diabetes. Aim of the present study was to evaluate the effect of quercetin, a bioflavonoid on thermal nociceptive responses in streptozotocin (STZ)-induced diabetic rats assessed by tail-immersion and hot plate methods. After 4-weeks of a single intravenous STZ injection (45 mg/kg body weight), diabetic rats exhibited a significant thermal hyperalgesia and cold allodynia along with increased plasma glucose and decreased body weights as compared with control rats. Chronic treatment with quercetin (10 mg/kg body weight; p.o) for 4-weeks starting from the 4th week of STZ-injection significantly attenuated the cold allodynia as well as hyperalgesia. Results indicate that quercetin, a natural antioxidant, may be helpful in diabetic neuropathy.

Animals↗

PubMed2003

Carvedilol, an antihypertensive drug with antioxidant properties, protects against glycerol-induced acute renal failure.

BACKGROUND/AIMS: 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 role of carvedilol, an antihypertensive drug with antioxidative potential, in glycerol-induced acute renal failure in rats. METHODS: Three groups of rats were employed in this study. Group 1 served as control, group 2 was given 50% glycerol (8 ml/kg, i.m.) and group 3 was given glycerol plus carvedilol (3 mg/kg, i.p.). 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 enzymatic activity of catalase, glutathione reductase and superoxide dismutase. RESULTS: Glycerol treatment resulted in marked renal oxidative stress and significantly deranged renal functions. Both of these factors were significantly improved by carvedilol treatment. Carvedilol, by its interaction with Fenton reaction chemistry and radical scavenging activity, protected the kidney against the oxidative stress and resultant renal dysfunction produced by glycerol. CONCLUSION: Based on these results, this study indicates the protective effect of carvedilol in this rhabdomyolysis-mimicking model.

Acute Kidney Injury↗

PubMed2003

Carvedilol and trimetazidine attenuates ferric nitrilotriacetate-induced oxidative renal injury in rats.

Intraperitoneal (i.p.) injection of ferric nitrilotriacetate (Fe-NTA) induces acute proximal tubular necrosis as a consequence of lipid peroxidation and oxidative tissue damage, which eventually leads to high incidence of renal adenocarcinoma in rodents. This study was designed to investigate the effect of carvedilol, an antihypertensive and trimetazidine, an antiischemic, both the drugs with additional antioxidative potentials, on Fe-NTA induced nephrotoxicity in rats. One hour after a single i.p. injection of Fe-NTA (8 mg iron per kg), a marked deterioration of renal architecture and renal function as evidenced by a sharp increase in blood urea nitrogen (BUN) and serum creatinine was observed. Fe-NTA induced a significant renal oxidative stress demonstrated by elevated thiobarbituric acid reacting substances (TBARS) and reduction in activities of renal catalase, superoxide dismutase (SOD) and glutathione reductase (GR). Pretreatment of animals with carvedilol (2 mg/kg, i.p.) as well as with trimetazidine (3 mg/kg, i.p.), 30 min before Fe-NTA administration markedly attenuated renal dysfunction, reduced elevated TBARS, restored the depleted renal antioxidant enzymes and normalised the renal morphological alterations. These results clearly demonstrate the role of oxidative stress and its relation to renal dysfunction, and suggest a protective effect of carvedilol and trimetazidine on Fe-NTA-induced nephrotoxicity in rats.

Animals↗

PubMed2003

Quercetin, a bioflavonoid, attenuates thermal hyperalgesia in a mouse model of diabetic neuropathic pain.

Diabetic neuropathic pain, an important microvascular complication in diabetes mellitus, has been recognised as one of the most difficult types of pain to treat. Lack of understanding of etiology involved, inadequate relief, development of tolerance and potential toxicity of classical antinociceptives warrant the investigation of newer agents to relieve pain. The aim of the present study was to explore the antinociceptive effect of a bioflavonoid, quercetin, both in control and streptozotocin (STZ)-induced diabetic mice. After 4 weeks of a single intraperitoneal injection of STZ (200 mg/kg), both control and diabetic mice were subjected to test thermal hyperalgesia by tail-immersion assay (warm water). Diabetic mice exhibited a significant hyperalgesia as compared with control mice. Quercetin (100 but not 50 mg/kg p.o.) produced a marked increase in tail-flick latencies in both diabetic and nondiabetic mice. Quercetin-induced increase in nociceptive threshold was reversed by naloxone (2 mg/kg i.p.), an opioid receptor antagonist. These preliminary results indicate an antinociceptive activity of quercetin, probably through modulation of opioidergic mechanism and point towards its potential to attenuate diabetic neuropathic pain.

Animals↗

PubMed2003

Catechin, a natural antioxidant 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). 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 catechin-a natural antioxidant 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(-1), i.m.), group 3, glycerol plus catechin (40 mg kg(-1), p.o. for 4 days, twice a day) and group 4 was given only catechin (40 mg kg(-1), p.o.), respectively. Renal injury was assessed by measuring serum creatinine, blood urea nitrogen (BUN), creatinine, and urea clearance. The oxidative stress was measured by renal malondialdehyde (MDA) levels, reduced glutathione levels and by enzymatic activity of catalase, glutathione reductase (GR) and superoxide dismutase (SOD). Glycerol administration resulted in a marked renal oxidative stress, significantly deranged the renal functions as well as renal morphology. All these factors were significantly improved by catechin treatment. Catechin, due to its antioxidative activity, reduced the toxicity of myoglobin in the renal tissues, and thus exerted a renoprotective effect in this rhabdomyolysis mimicking model.

Acute Kidney Injury↗

PubMed2003

Effect of U-74500A, a 21-aminosteroid on renal ischemia-reperfusion injury in rats.

Renal ischemia-reperfusion injury constitutes the most common pathogenic factor for acute renal failure and is the main contributor to renal dysfunction in allograft recipients and revascularization surgeries. Many studies have demonstrated that reactive oxygen species play an important role in ischemic acute renal failure. The aim of the present study was to investigate the effects of the synthetic antioxidant U-74500A, a 21-aminosteroid in a rat model of renal ischemia-reperfusion injury. Renal ischemia-reperfusion was induced by clamping unilateral renal artery for 45 min followed by 24 h of reperfusion. Two doses of U-74500A (4.0 mg/kg, i.v.) were administered 45 min prior to renal artery occlusion and then 15 min prior to reperfusion. Tissue lipid peroxidation was measured as thiobarbituric acid reacting substances (TBARS) in kidney homogenates. 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 hematoxylin-eosin stained sections of the kidneys. Ischemia-reperfusion 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 sham operated rats. The ischemic kidneys of rats showed severe hyaline casts, epithelial swelling, proteinaceous debris, tubular necrosis, medullary congestion and hemorrhage. U-74500A markedly attenuated elevated levels of TBARS as well as morphological changes, but did not improve renal dysfunction in rats subjected to renal ischemia-reperfusion. These results clearly demonstrate the in vivo antioxidant effect of U-74500A, a 21-aminosteroid in attenuating renal ischemia-reperfusion injury.

Animals↗