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.     

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.     

Contribution of renal oxygenases to glycerol-induced acute renal failure in the rat

Administration of glycerol produces acute renal failure (ARF) accompanied by profound vasoconstriction. It was hypothesized that impaired arachidonic acid metabolism may contribute to the vasoconstriction through alteration of renal eicosanoids or endothelin-1 or angiotensin II stimulation of renal oxygenases. Arachidonic acid (5, 10, 25 microg) in the control kidney produced increases in perfusion pressure of 15 +/- 9, 18 +/- 8, and 43 +/- 18 mm Hg, respectively. These responses were increased 1.5-fold in glycerol-induced renal failure (p < 0.01). Indomethacin (10 microM), the cyclooxygenase inhibitor, converted arachidonic acid vasoconstriction to epoxide-mediated vasodilator responses, which were unchanged in ARF. In ARF, 5,8,11,14-eicosatetraynoic acid (10 microM), the all-purpose inhibitor of arachidonic acid metabolism; indomethacin (10 microM), a cyclooxygenase inhibitor; 5,8,11-eicosatriyenoic acid (2.5 microM), the 5- and 12-lipoxygenase inhibitor; or aminobenzotriazole (50 mM), the cytochrome P-450 monooxygenase inhibitor, markedly attenuated arachidonic acid-induced vasoconstriction by 73 +/- 11% (p < 0.01), 89 +/- 1% (p < 0.01), 62 +/- 11% (p < 0.01), and 82 +/- 2% (p < 0.01), respectively. In ARF, angiotensin II-induced vasoconstriction was amplified by 67% (p < 0.01). Eicosatetraynoic acid, eicosatriyenoic acid, and aminobenzotriazole reduced these responses by 33 +/- 6% (p < 0.05), 53 +/- 6% (p < 0.01), and 52 +/- 11% (p < 0.05), respectively. Vasoconstriction by endothelin-1 was unchanged in ARF (24 +/- 17%). However, indomethacin attenuated endothelin-1 vasoconstriction by 41 +/- 11% (p < 0.05), whereas eicosatriyenoic acid and aminobenzotriazole were without effect. These data suggest that the increased renal vascular reactivity in ARF in response to arachidonic acid involves a relatively greater production of cyclooxygenase metabolites than monoxygenase- or lipoxygenase-derived eicosanoid metabolites. Furthermore, increased angiotensin II vasoconstriction is predominantly through lipoxygenase and monoxygenase metabolic pathways, whereas for endothelin-1, increased cyclooxygenase-derived vasoconstrictor metabolites play a significant role in its amplified vasoconstrictor effect in glycerol-induced ARF.     

松花粉对甘油诱导大鼠急性肾衰竭的保护作用

目的：研究松花粉对甘油诱发大鼠急性肾衰竭（acute renal failure,ARF）的保护作用及机制。方法：采用双侧后肢注射50%甘油溶液（10 mL·kg-1）诱发大鼠成急性肾衰竭模型,检测大鼠血清肌酐（Scr）、血清尿素氮（BUN）的含量,肾组织中超氧化物歧化酶（SOD）的活性,谷胱甘肽（GSH）、丙二醛（MDA）的含量,同时测定肾组织中一氧化氮（NO）的含量和诱导型一氧化氮合酶（iNOS）的活性;HE染色观察肾病理组织形态学变化。结果：与空白组大鼠相比,模型组大鼠血清Scr和BUN的含量明显上升,肾组织中SOD的活性和GSH的含量显著降低,MDA的含量显著升高;组织病理检查发现,模型组大鼠肾小管损伤明显,肾皮质细胞部分脱落,肾小球肿胀,间质炎性侵润明显。给予松花粉治疗后,可显著降低ARF大鼠血清Scr和BUN,升高肾组织中SOD的活性、GSH的含量,降低MDA的含量,同时发现,松花粉可明显降低肾组织中NO的含量和iNOS的活性,并显著降低肾组织损伤。结论：松花粉对甘油致大鼠ARF具有治疗作用,其作用机制可能与抑制iNOS的活性,降低体内NO过多产生,降低NO相关的脂质过氧化过程有关。     

Dietary curcumin does not protect kidney in glycerol-induced acute renal failure.

Generation of reactive oxygen species significantly contribute to the pathogenesis of renal injury induced by myoglobin release. The present study was performed to investigate the effects of dietary curcumin, a natural antioxidant isolated from plant Curcuma longa, in an experimental model of myoglobinuric acute renal failure. Rats received curcumin at an oral dose of 100mg/kg/day for 30 days. Renal injury was induced with injection of hypertonic glycerol (10 ml/kg 50% solution) in hind limb muscle with blood urea of 57.8+/-7.2 vs. 7.72+/-1.03 mmol/l and serum creatinine of 444.4+/-61.3 vs. 51.8+/-10.6 micromol/l, in glycerol-induced acute renal failure (ARF) vs. control rats, respectively. After 48 h rats were sacrificed and thiobarbituric acid reactive substance (TBARS), glutathione, carbonyl content and kidney cortex brush border peptidase activities were determined in serum, kidney and liver. Rats that received curcumin in addition to glycerol had significantly lower TBARS in serum but not in kidney and liver. Carbonyl content in kidney and liver was significantly elevated in curcumin and glycerol treated rats and improved in animals treated with curcumin and glycerol together. The activities of kidney cortex enzymes, aminopeptidase N, angiotensinase A and dipeptidyl peptidase IV, were reduced in glycerol as well as in curcumin treated rats. The results obtained in this study provided additional evidence that despite its limited antioxidant activity curcumin did not protect kidney in myoglobinuric model of ARF.     

Protective effect of γ-aminobutyric acid against glycerol-induced acute renal failure in rats

To investigate the effect of γ-aminobutyric acid (GABA) on acute renal failure, we used a rat model of acute tubular necrosis induced by glycerol. After deprivation of water for 6 h, the rats received an injection of 50% glycerol into the muscle of the rear limb at 10 ml/kg body weight. GABA was then administered orally to the rats (100 or 500 mg/kg body weight/day) once every 12 h for 3 days. The rats with acute renal failure showed arrested body weight gain and an increase of kidney weight, whereas oral administration of GABA attenuated the physiological changes induced by acute renal failure. However, GABA administration had no significant effect on increased urine volume. Oral administration of GABA at a dose of 100 or 500 mg/kg body weight/day for 3 days significantly improved the markedly elevated levels of blood urea nitrogen and creatinine and the reduced creatinine clearance related to progression of renal failure. Moreover, the rats with acute renal failure exhibited high levels of fractional excretion of sodium (FE_Na) due to alteration of tubule function following injection of glycerol. However, administration of GABA lowered the FE_Na levels dose-dependently. Furthermore, urine osmolarity was markedly reduced in control rats with acute renal failure as compared with normal rats, whereas it was significantly increased by administration of GABA at a dose of 500 mg/kg body weight/day. These results indicate that GABA has potential as a therapeutic agent against the renal damage involved in acute renal failure.     

Effect of 8-phenyltheophylline, enprofylline and hydrochlorothiazide on glycerol-induced acute renal failure in the rat

The adenosine antagonist 8-phenyltheophylline (8-PT) is a diuretic in normal rats and can ameliorate glycerol-induced acute renal failure (ARF) in this species. To define which action of 8-PT is important in its salutary effect in ARF, we have compared its effects with those of enprofylline (a xanthine with little affinity for adenosine receptors) and with those of the tubular diuretic hydrochlorothiazide. In one series of experiments, groups of rats with ARF of 24 h duration were given a single dose of drug or vehicle. Only 8-PT enhanced urine volume when compared with the vehicle-treated group. In a second set of experiments, groups of glycerol-injected rats received drug or vehicle treatment (i.p.) twice daily for 2 days. Rats which received a course of 8-PT treatment had significantly lower plasma urea and creatinine concentrations, a higher glomerular filtration rate, a lower kidney weight and improved kidney morphology when compared with vehicle-treated rats. The only beneficial effect noted after enprofylline treatment was an improved kidney morphology. Hydrochlorothiazide treatment compared with vehicle treatment did not ameliorate any index of renal function but resulted in significant elevations in plasma urea and creatinine levels. The inability of enprofylline or hydrochlorothiazide to mimic the effects of 8-PT in ARF indicate that the effects of 8-PT are probably associated with adenosine receptor blockade and not with a tubular diuretic action.     

Protective effects of FK453, a potent nonxanthine adenosine A1 receptor antagonist,on glycerol-induced acute renal failure in rats

The purpose of the present study was to examine the protective effect of FK453, (+)-(R)-1-[(E)-3-(2-phenylpyrazolo [1,5-a] pyridin-3-yl) acryloyl]-2-piperidine ethanol, a potent non-xanthine (adenosine A₁ receptor antagonist, on glycerol-induced acute renal failure (ARF) in rat in comparison with the effects of FR113452 (S-(-) enantiomer of FK453), 1,3-dipropyl-8-cyclopentyl-xanthine (adenosine A₁ receptor antagonist), theophylline (nonselective adenosine receptor antagonist), CGS15943 [1,2,4] triazolo [1,5-C] quinazolone, adenosine A_2A receptor antagonist), and typical diuretics (hydrochlorothiazide and furosemide). FK453 (1 and 10 mg/kg orally) significantly reduced serum creatinine and urea concentrations in 25% glycerol (10 ml/kg intramuscularly)-induced ARF by protective treatment. The effect was similar to that of 1,3-dipropyl-8-cyclopentyl-xanthine and theophylline. FR113452 and CGS15943 had little effect on serum creatinine and urea concentrations. In contrast, hydrochlorothiazide and furosemide increased serum creatinine and urea concentrations. FK453, hydrochlorothiazide, and furosemide did not have any effect on either serum creatinine or urea concentration in 25% glycerol-induced ARF by therapeutic treatment. In 50% glycerol (10 ml/kg im)-induced ARF, FK453 reduced serum creatinine and urea concentrations, and increased urine volume and creatinine clearance. The results of the present study showed that FK453, a potent nonxanthine adenosine A₁ receptor antagonist, ameliorated glycerol-induced ARF in the rat. The findings support the idea that adenosine is an important factor in the development of glycerol-induced ARF in the rat and that the protective effect of adenosine receptor antagonist is mediated via the adenosine A₁ receptor. Drug Dev. Res. 39:47–53 © 1997 Wiley-Liss, Inc.     

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.     

Effects of glycerol-induced acute renal failure on tissue glutathione and glutathione-dependent enzymes in the rat

The activities of tissue glutathione (reduced and oxidized) and glutathione-dependent enzymes such as glutathione S-transferase (GSH S-transferase), glutathione reductase (GSSG reductase) and glutathione peroxidase (GSH-Px) were determined for control and uremic rats. Acute renal failure (ARF) was produced by glycerol-water injection. Cytosolic and microsomal GSH S-transferase activity in the kidney was decreased by 38% and 15%, respectively. Hepatic microsomal GSH S-transferase was also decreased by 40% in uremic rats. GSH-Px activity was decreased by 51% in the cytosolic fraction and 33% in the microsomal fraction in the kidney, but was not affected in the liver and whole blood. GSSG reductase activity was also decreased by 48% in the cytosolic fraction in the kidney of uremic rats. In whole blood, however, GSSG reductase activity was increased by 12-fold (0.66 +/- 0.12 mumol NADPH oxidized/min/ml blood in the control; 8.03 +/- 3.29 mumol NADPH oxidized/min/ml blood in uremia). Although the total glutathione concentrations were not significantly affected, the GSSG/GSH ratio, which is an indication of oxidative stress, was significantly increased in the liver and whole blood of uremic rats. In addition to the decreases in hepatic and renal GSH S-transferase activities, which is important in drug disposition, ARF caused decreases in GSSG reductase and GSH-Px activity, which are essential for the protection against lipid peroxidation.     

Cardiovascular responses in rats with glycerol-induced acute renal failure

Autonomic and cardiovascular function were assessed in rats with glycerol-induced acute renal failure (ARF). Rats with ARF had significantly lower mean arterial blood pressure and heart rates and significantly elevated plasma noradrenaline concentrations. The chronotropic responses to right cervical sympathetic and vagal stimulation were diminished in rats with ARF. The pressor and depressor responses to noradrenaline and nitroprusside respectively when expressed as a change in mmHg pressure were significantly reduced in rats with ARF when compared to controls. However, when the depressor responses to nitroprusside were expressed as a percentage fall in basal mean arterial pressure, with the exception of the response to a dose of 10 micrograms kg-1, there were no significant differences between control and uraemic rats. The present findings show that in the rat, changes in cardiovascular responsiveness occur after a brief period of uraemia which are similar to those observed in patients and rats with chronic renal failure.     

Effect of the adenosine antagonist 8-phenyltheophylline on glycerol-induced acute renal failure in the rat.

8-Phenyltheophylline (8-PT)(10 mg kg-1) or its vehicle(1 ml kg-1) were administered intravenously or intraperitoneally twice daily over 48 h to rats with acute renal failure (ARF) induced by intramuscular (i.m.) injection of glycerol. Rats treated with 8-PT i.v. had significantly lower plasma urea and creatinine levels at 24 and 48 h compared to untreated animals. The vehicle also reduced plasma urea and creatinine when compared to untreated controls. However, plasma urea levels in 8-PT-treated rats were significantly lower than in vehicle-treated animals at 24 and 48 h after both i.v. and i.p. administration. Plasma creatinine concentrations also tended to be lower in the 8-PT-treated group. [3H]-inulin clearance at 48 h after i.m. glycerol was significantly greater in rats dosed i.p. with 8-PT compared to either untreated or vehicle treated rats. Examination of kidneys taken from rats 48 h after i.m. glycerol showed that 8-PT treatment significantly reduced renal damage and kidney weight compared to the untreated or vehicle-treated groups. In a 7 day study all the rats which received 8-PT i.p. survived whilst in the vehicle and untreated groups the mortality rates were 12 and 21% respectively. In a separate series of experiments 8-PT (10 mg kg-1, i.v. or i.p.) was found to antagonize adenosine-induced bradycardia in conscious rats for up to 5 h. There is no clear explanation for the partial protection afforded by the vehicle but it may be related to either its alkalinity or an osmotic effect produced by the polyethylene glycol component.(ABSTRACT TRUNCATED AT 250 WORDS)     

Further characterization of the protective effect of 8-cyclopentyl-1,3-dipropylxanthine on glycerol-induced acute renal failure in the rat.

In the rat, treatment with the alkylxanthine 8-cyclopentyl-1,3-dipropylxanthine (CPX) at a dose of 0.1 mg kg-1 antagonizes adenosine-induced falls in renal blood flow and reduces the severity of glycerol-induced acute renal failure. Treatment of glycerol-injected rats with 0.03 mg kg-1 of CPX resulted in no significant improvements in a range of indices of renal function. However, treatment with 0.1 or 0.3 mg kg-1 doses of CPX did significantly ameliorate acute renal failure although there were no significant differences in the degree of protection of renal function afforded by these two doses. In glycerol-injected rats, 0.1 or 0.3 mg kg-1 CPX administered either as a single dose or repeated doses every 12 h for two days did not inhibit renal phosphodiesterase. Thus the beneficial effects of CPX can be produced by doses that have no effect on renal phosphodiesterase activity whereas 0.1 mg kg-1 of CPX has been shown previously to antagonize the actions of adenosine. The findings provide further evidence that the beneficial effect of CPX in glycerol-induced acute renal failure is a consequence of adenosine antagonism and not phosphodiesterase inhibition.     

Amelioration of glycerol-induced acute renal failure in the rat with 8-cyclopentyl-1,3-dipropylxanthine.

1. Previous studies have shown that 8-phenyltheophylline (8-PT), a non-selective antagonist at adenosine A1- and A2-receptors, can ameliorate the severity of glycerol-induced acute renal failure (ARF) in the rat. In the present study we have examined the effects of an antagonist with selectivity for adenosine A1-receptors (8-cyclopentyl-1,3-dipropylxanthine, CPX) on the development of ARF. 2. In the anaesthetised rat 8-PT (4 mg kg-1, i.v.) and CPX (0.1 mg kg-1, i.v.) antagonised adenosine-evoked responses which are thought to be mediated via A1-receptors (bradycardia and decrease in renal blood flow). The agonist dose-ratio produced by CPX was equal to or greater than that found with 8-PT (heart rate and renal blood flow respectively). The hypotensive response to adenosine which is predominantly due to A2-receptor activation was also antagonised by 8-PT, whereas CPX was a much less effective antagonist of this response. 3. Administration of CPX (0.1 mg kg-1, i.v.; twice daily for two days) significantly attenuated the increase in plasma levels of urea and creatinine, the increased kidney weight and the renal tubule damage observed in rats 2 days following induction of ARF with intramuscular glycerol injection. In addition treatment with CPX significantly enhanced the clearances of inulin and p-aminohippurate. 4. After glycerol injection, the mortality rate over 7 days in untreated and vehicle-treated rats was 43% and 21% respectively. In contrast, all animals treated with CPX survived over the 7 day observation period. 5. These results support the suggestion that adenosine is an important factor in the development of ARF and indicate that this effect of the purine is likely to be mediated via an adenosine A1-receptor.     

The effect of glycerol-induced acute renal failure upon cardiac reactivity in the rat: influence of indomethacin treatment and renal pedicle ligation

Cardiac chronotropic responses to isoprenaline, carbachol and electrical stimulation of the cervical sympathetic and vagal nerves were recorded in rats with glycerol-induced acute renal failure (ARF) and control rats. The experiments involving electrical stimulation of cardiac nerves were performed in rats which either had been pretreated with indomethacin (1 mg kg-1 twice daily for 2 days) or had undergone acute bilateral renal pedicle ligation. The findings from this investigation indicate that the reduced chronotropic responses to vagal stimulation in rats with glycerol-induced ARF are due to a reduction in acetylcholine release mediated by prostaglandins possibly originating from the damaged kidneys. The diminished response to cervical sympathetic stimulation results from a decreased postsynaptic response to beta-adrenoceptor stimulation.     

肾安康胶囊对急性肾功能衰竭模型大鼠的保护作用

目的:研究肾安康胶囊改善急性肾功能衰竭(ARF)模型大鼠的血生化指标和排尿作用。方法:灌胃给予血红蛋白尿模型大鼠不同剂量的肾安康胶囊后,取血观察其血尿素氮(BUN)和血清肌酐(Scr)水平,以及每天排尿量。结果:该药高、低剂量组对血红蛋白尿模型大鼠的BUN水平均无明显改变;而能不同程度的降低模型大鼠的Scr水平;其高、低剂量组均可改善模型大鼠的排尿量。结论:肾安康胶囊对急性肾功能衰竭模型大鼠有一定的保护作用。     

Amelioration of glycerol-induced acute renal failure in the rat with 8-phenyltheophylline: timing of intervention

The importance of timing and duration of 8-phenyltheophylline (8-PT) administration in determining its beneficial action in glycerol-induced acute renal failure (ARF) was investigated by examining the effects of a single dose of 8-PT given immediately following (0 h) glycerol injection and at 1 and 3 h after glycerol injection. 8-PT when given at 0 h significantly lowered plasma urea and creatinine concentrations and significantly increased inulin clearance when compared both to untreated animals and those that received the vehicle for the drug. By contrast, 8-PT when administered at 1 h afforded no protective effect on renal function and, when injected at 3 h, the only significant effect was lowered plasma creatinine levels when compared to untreated rats; at this latter time it did not lower plasma urea levels or improve inulin clearance. None of the 8-PT injections attenuated the increase in kidney weight associated with ARF or reduced the kidney damage as assessed by histological examination. The results show that a single administration of 8-PT made immediately following glycerol injection can ameliorate the biochemical and functional indices of impaired renal function, but does not produce an improvement in kidney morphology.     

Effects of caffeic acid phenethyl ester on glycerol-induced acute renal failure in rats

1. Free radicals and nitric oxide (NO) play a crucial role in the pathogenesis of myoglobinuric acute renal failure (ARF). The aim of the present study was to investigate the effects of caffeic acid phenethyl ester (CAPE), an anti-oxidant, on the myoglobinuric ARF induced by intramuscular hypertonic glycerol injection. 2. Thirty rats were divided equally into three groups. Rats in group 1 were given saline and those in groups 2 and 3 were injected with glycerol (10 mL/kg, i.m.). Concomitant and 24 h after glycerol injection, CAPE (10 micromol/kg, i.p.) was administered to group 3 rats. Forty-eight hours after glycerol injection, blood samples and kidney tissues of rats were taken under anaesthesia. 3. Plasma concentrations of urea, creatinine, malondialdehyde (MDA) and NO were determined, as were superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities and MDA levels in kidney tissues. Kidney morphology was also investigated. 4. In the group receiving CAPE, although SOD enzyme activity was found to be increased, we failed to find any protective effect of CAPE on other parameters investigated. Moreover, although CAPE significantly decreased NO levels, it increased plasma concentrations of urea and MDA. 5. We suggest that the effect of CAPE in decreasing NO concentrations may further increase the renal ischaemia in this model. Thus, CAPE may have a worsening rather than beneficial effect under these conditions in this model of ARF.     

Pharmacological investigations of Punica granatum in glycerol-induced acute renal failure in rats

Objective:

The present study was designed to investigate the ameliorative potential and possible mechanism of hydroalcoholic extract of flowers of P. granatum in glycerol-induced acute renal failure (ARF) in rats.

Materials and Methods:

The rats were subjected to rhabdomyolytic ARF by single intramuscular injection of hypertonic glycerol (50% v/v; 8 ml/kg) and the animals were sacrificed after 24 hours of glycerol injection. The plasma creatinine, blood urea nitrogen, creatinine clearance, and histopathological studies were performed to assess the degree of renal injury.

Results:

Pretreatment with hydroalcoholic extract of flowers of P. granatum (125 and 250 mg/kg p.o. twice daily for 3 days) significantly attenuated hypertonic glycerol-induced renal dysfunction in a dose-dependent manner. BADGE (Bisphenol-A-diglycidyl ether) (30 mg/kg), a peroxisome proliferator-activated receptor (PPAR)-γ antagonist, and N(omega)-nitro-l-arginine-methyl ester (L-NAME) (10, 20, and 40 mg/kg), nitric oxide synthase inhibitor, were employed to explore the mechanism of renoprotective effects of Punica granatum. Administration of BADGE (30 mg/kg) and L-NAME (40 mg/kg) abolished the beneficial effects of P. granatum in glycerol-induced renal dysfunction.

Conclusion:

Hydroalcoholic extract of flowers of P. granatum has ameliorative potential in attenuating myoglobinuric renal failure and its renoprotective effects involve activation of PPAR-γ and nitric oxide-dependent signaling pathway.