Protective Effect of a Bioflavonoid Proanthocyanidin-BP1 in Glycerol-Induced Acute Renal Failure in the Rat: Renal Stereological Study

Renal ischemia as well as oxygen metaholites ploy an important role in renal Injury during myoglobinuric acute renal failure (ARF). On the other hand, flavonoids. a diverse group of constituents naturally occurring in plants, have a strong antioxidative activity, and have been implicated in vascular relaxation. In this study the protective effect of a new bioflavonoid proanthocvanidin-BP1 (BP1), extracted from seeds of grapes, was evaluated in glycerol-induced ARF in rats. Stereological methods were used to quantify changes in renal morphology associated with ARF. Volume density of tubular lumen and intratubular cast formations, nuclear parameters (area, diameter, volume) of epithelial cells in the cortical proximal tubules, and glomerular parameters (surface area, diameter, volume, perimeter) were estimated on kidney sections of rats treated either with 50% glycerol (8 ml/kg i.m.) alone. BP1 (20 mg/kg i.p.) in addition to glycerol, or BP1 alone. It was noted that the volume density of tubular lumen and cast formations were significantly lower (p < 0.001) in kidneys of the rats treated with BP1 in addition to glycerol, compared with those treated with glycerol alone. There were no significant differences in glomerular and nuclear parameters between glycerol treated, and BP1 in addition to glycerol treated rats. Renal function was significantly improved in rats treated with BP1 in addition to glycerol. The results suggest that BP1 is a protective agent in glycerol model of ARF. This effect is probably due to the antioxidative activity of BP1 and reduced toxicity of myoglobin in renal tissue. Moreover, it is possible that the ability of BP1 to protect the kidney is dependent upon renal vascular relaxation. The potential beneficial effects of bioflavonoid-BP1 demonstrated in experimental ARF could be considered in therapy of myoglobinuric ARF.     

Effects of melatonin administration to rats with glycerol-induced acute renal failure

Melatonin, the pineal hormone with antioxidative properties was administered to rats with glycerol-induced myoglobinuric acute renal failure (Gly-ARF). This model is characterized by acute tubular necrosis mediated by heme-iron oxidative stress. Rats received melatonin (20 mg/kg) concomitant and 3 h after glycerol injection. Gly-ARF rats showed at 24 h a 78% reduction in glomerular filtration rate, whereas this decrement was significantly reduced to 35% in the melatonin treated Gly-ARF rats. Tubular function evaluated by tubular reabsorption of sodium and lithium was also preserved in melatonin treated rats. The histologic analysis revealed extensive cortical tubular necrosis that was significantly reduced by melatonin treatment. The renal concentration of malondialdehyde (MDA) was increased 6 h after glycerol injection in Gly-ARF and this elevation was prevented when melatonin was administered. Renal concentration of reduced glutathione (GSH) was decreased at 6 h in Gly-ARF and melatonin did not reverse this decrease. It was concluded that melatonin administration attenuated the renal injury in the glycerol model of acute renal failure and reduced kidney oxidative stress through a GSH-independent mechanism.     

EFFECTS OF MELATONIN ADMINISTRATION TO RATS WITH GLYCEROL-INDUCED ACUTE RENAL FAILURE

Melatonin, the pineal hormone with antioxidative properties was administered to rats with glycerol-induced myoglobinuric acute renal failure (Gly-ARF). This model is characterized by acute tubular necrosis mediated by heme-iron oxidative stress. Rats received melatonin (20 mg/kg) concomitant and 3 h after glycerol injection. Gly-ARF rats showed at 24 h a 78% reduction in glomerular filtration rate, whereas this decrement was significantly reduced to 35% in the melatonin treated Gly-ARF rats. Tubular function evaluated by tubular reabsorption of sodium and lithium was also preserved in melatonin treated rats. The histologic analysis revealed extensive cortical tubular necrosis that was significantly reduced by melatonin treatment. The renal concentration of malondialdehyde (MDA) was increased 6 h after glycerol injection in Gly-ARF and this elevation was prevented when melatonin was administered. Renal concentration of reduced glutathione (GSH) was decreased at 6 h in Gly-ARF and melatonin did not reverse this decrease. It was concluded that melatonin administration attenuated the renal injury in the glycerol model of acute renal failure and reduced kidney oxidative stress through a GSH-independent mechanism.     

Protective effect of resveratrol, a polyphenolic phytoalexin on glycerol-induced acute renal failure in rat kidney

Rhabdomyolysis-induced myoglobinuric acute renal failure (ARF) accounts for about 10% to 40% of all cases of ARF. Reactive oxygen intermediates have been demonstrated to play an etiologic role in myoglobinuric renal failure. This study was designed to investigate the effect of resveratrol, a polyphenolic phytoalexin in glycerol-induced ARF in rats. Seven 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 IV, and V were given glycerol plus resveratrol (2 mg/kg, 5 mg/kg, and 10 mg/kg p.o. route, respectively) 60 min prior to the glycerol injection; group VI received L-NAME (10 mg/kg, i.p.) along with glycerol and resveratrol (5 mg/kg), group VII animals received L-NAME (10 mg/kg) 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 and reduced glutathione levels, and by enzymatic activity of catalase, glutathione reductase, and superoxide dismutase. Tissue and urine nitrite levels were measured as an index of total nitric oxide levels. Glycero 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 resveratrol (5 and 10 mg/kg) 60 min prior to glycerol injection markedly attenuated the fall in nitric oxide levels, renal dysfunction, morphologic alterations, reduced elevated thiobarbituric acid reacting substances, and restored the depleted renal antioxidant enzymes. This protection afforded by resveratrol was significantly reversed by cotreatment of L-NAME along with resveratrol, clearly indicating that resveratrol exerts its protective effect through nitric oxide release along with the antioxidative effect in glycerol-induced ARF.     

Acute renal failure in rhabdomyolysis.

Fifteen to 30% of patients develop acute renal failure (ARF) following rhabdomyolysis and rhabdomyolysis accounts for 5 to 9% of all ARF. Experimental studies revealed two critical factors that predispose to myoglobinuric ARF: hypovolemia/dehydration and aciduria. At the nephron level, three basic mechanisms underlie heme protein toxicity: renal vasoconstriction with decreased renal blood flow, intraluminal cast formation and direct heme protein-induced cytotoxicity. During the early phase of myoglobinuric ARF, hemodynamic process are mainly involved in glomerumar filtration rate decrease while tubular mechanisms occur in the late phase. Critical factors which predispose to myoglobinuric ARF in animal models--i.e. hypovolemia/dehydration and aciduria--are also encountered in human epidemiological studies. Prevention of myoglobinuric ARF rely on rapid and adequate correction of fluid deficits with saline, bicarbonates and mannitol. The choice of hemodialysis technique in the case of constituted ARF strongly depends on the site of intervention, especially in the case of rescue operation. The care of myoglobinuric ARF in intensive care unit do not differ from this of ARF from other causes.     

Effects of N-acetylcysteine on myoglobinuric-acute renal failure in rats

Oxygen metabolites play an important role in renal injury during myoglobinuric acute renal failure (ARF). This study was designed to determine the protective influence of N-acetylcysteine (NAC), a hydroxyl radical scavenger, and treatment in an experimental model of myoglobinuric-ARF induced by intramuscular injection of hypertonic glycerol in rats. The rats were randomly distributed into five groups: Group 0 (n = 10), was assigned to receive 2mL saline (0,9%) intraperitoneally (ip); Group 1 (n = 10), NAC ip in a dose of 0 mg/100 g of body weight 30 min before the intramuscular (im) injection of 50% glycerol (10 mg/kg); Group 2 (n = 10), received saline 0,9% ip in a equivalent volume of NAC in Group I before the im injection of glycerol; Group 3 (n = 10), received NAC ip in a dose of 10 mg/100 g after im injection of glycerol; Group 4 (n = 10), saline 0,9% ip in a equivalent volume of NAC of the Group 3 after im administration of glycerol. After 24 h rats were sacrificed and kidney morphology and renal function were determined. A severe renal failure was produced by glycerol injection in the Groups 1, 2, 3, and 4, with significant tubular proximal necrosis and cast formation, and creatinine and urea concentrations were elevated in these groups without significant differences among groups, but Group 0 where the values were significantly lower. The results of this study suggests that ip administration of NAC in rats before or after glycerol injection do not confer protection against impairment of renal function under these conditions in this model of myoglobinuric-ARF.     

Experimental myoglobinuric acute renal failure: the effect of vitamin C

During times of war and natural disasters, rhabdomyolysis-induced myoglobinuric acute renal failure (ARF) can assume epidemic proportions. Free radicals play an important role in the pathogenesis of myoglobinuric ARF. Vitamin C is a major antioxidant, scavenging free radicals. We have not found any studies on the effect of vitamin C on myoglobinuric ARF. Thus, we aimed to investigate the effects of vitamin C on the myoglobinuric ARF formed by glycerol in rats. Three groups of rats were employed in this study. Group 1 served as control, group 2 was given 50% glycerol (10 mL/kg, i.m.), and group 3 was given glycerol plus vitamin C (20 mg/kg, i.p. for four days). Ninety-six hours after glycerol injections, blood samples and kidney tissues were taken from the anesthetized rats. Urea and creatinine levels in plasma; N-acetyl-beta-D-glucosaminidase activity in urine; malondialdehyde levels, superoxide dismutase and catalase enzyme activity in kidney tissue were determined. Histopathological changes and iron accumulation in the kidney tissue were evaluated. In this study, glycerol administration led to marked renal oxidative stress and severe renal functional and morphological deterioration. The treatment of animals with vitamin C partially corrected the renal dysfunction and morphological impairment. In this respect, vitamin C appears to be a promising candidate for the prevention of rhabdomyolysis-induced ARF. Higher dosages of vitamin C than in 20 mg/kg may be beneficial for better functional and morphological recovery in this model ARF.     

Protective Effect of Resveratrol,a Polyphenolic Phytoalexin on Glycerol-Induced Acute Renal Failure in Rat Kidney

Rhabdomyolysis-induced myoglobinuric acute renal failure (ARF) accounts for about 10% to 40% of all cases of ARF. Reactive oxygen intermediates have been demonstrated to play an etiologic role in myoglobinuric renal failure. This study was designed to investigate the effect of resveratrol, a polyphenolic phytoalexin in glycerol-induced ARF in rats. Seven groups of rats were employed in this study, group I served as control; group II was given 50% glycerol (8mL/kg, intramuscularly); groups III, IV, and V were given glycerol plus resveratrol (2mg/kg, 5mg/kg, and 10mg/kg p.o. route, respectively) 60 min prior to the glycerol injection; group VI received L-NAME (10mg/kg, i.p.) along with glycerol and resveratrol (5 mg/kg), group VII animals received L-NAME (10 mg/kg) 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 and reduced glutathione levels, and by enzymatic activity of catalase, glutathione reductase, 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. Pretreatment of animals with resveratrol (5 and 10 mg/kg) 60 min prior to glycerol injection markedly attenuated the fall in nitric oxide levels, renal dysfunction, morphologic alterations, reduced elevated thiobarbituric acid reacting substances, and restored the depleted renal antioxidant enzymes. This protection afforded by resveratrol was significantly reversed by cotreatment of L-NAME along with resveratrol, clearly indicating that resveratrol exerts its protective effect through nitric oxide release along with the antioxidative effect in glycerol-induced ARF.     

Reversal of experimental myoglobinuric acute renal failure with bioflavonoids from seeds of grape

Rhabdomyolysis may account for about 10% of all cases of acute renal failure (ARF). This study was performed to explore the protective influence of proanthocyanidins from seeds of grape in an experimental model of myoglobinuric ARF. Rats were injected with 50% glycerol (8 mL/kg, im) followed immediately and daily in the next three days by ip proanthocyanidins (20 mg/kg) or saline. After 96 h rats were sacrificed and kidney morphology, kidney cortex peptidase activities, and malondialdehyde (MDA) content were determined. A moderate renal failure was produced by glycerol injection with blood urea of 31.8+/-11.0 vs. 7.68+/-0.24 m mol/L, and serum creatinine of 153. +/-38.2 vs. 39.6+/-9.0 micromol/L, in glycerol-induced ARF vs. control rats, respectively. Rats that received proanthocyanidins in addition to glycerol had significantly lower (p < 0.01) blood urea and serum creatinine levels compared to those receiving glycerol alone. These functional differences between the glycerol and glycerol plus proanthocianidins groups were also confirmed histologically. Kidney cortex dipeptidylpeptidase IV (DPP IV) activity was not significantly changed in glycerol-induced ARF, however, markedly increased after proanthocyanidins treatment. Kidney cortex malondialdehyde content was found significantly increased in glycerol-induced ARF over control level, and was markedly reduced by proanthocyanidin treatment. Taken together, these results provide strong evidence for the protective role of proanthocyanidins from seeds of grape in glycerol-induced ARF. The effect is probably due to the antioxidant activity of proanthocyanidins and to increased expression of kidney cortex DPP IV with effective degradation of TNF-alpha. This may provide therapeutic opportunities of preventing and/or treating myoglobinuric ARF in humans.     

Experimental Myoglobinuric Acute Renal Failure: The Effect of Vitamin C

During times of war and natural disasters, rhabdomyolysis-induced myoglobinuric acute renal failure (ARF) can assume epidemic proportions. Free radicals play an important role in the pathogenesis of myoglobinuric ARF. Vitamin C is a major antioxidant, scavenging free radicals. We have not found any studies on the effect of vitamin C on myoglobinuric ARF. Thus, we aimed to investigate the effects of vitamin C on the myoglobinuric ARF formed by glycerol in rats. Three groups of rats were employed in this study. Group 1 served as control, group 2 was given 50% glycerol (10 mL/kg, i.m.), and group 3 was given glycerol plus vitamin C (20 mg/kg, i.p. for four days). Ninety-six hours after glycerol injections, blood samples and kidney tissues were taken from the anesthetized rats. Urea and creatinine levels in plasma; N-acetyl-beta-D-glucosaminidase activity in urine; malondialdehyde levels, superoxide dismutase and catalase enzyme activity in kidney tissue were determined. Histopathological changes and iron accumulation in the kidney tissue were evaluated. In this study, glycerol administration led to marked renal oxidative stress and severe renal functional and morphological deterioration. The treatment of animals with vitamin C partially corrected the renal dysfunction and morphological impairment. In this respect, vitamin C appears to be a promising candidate for the prevention of rhabdomyolysis-induced ARF. Higher dosages of vitamin C than in 20 mg/kg may be beneficial for better functional and morphological recovery in this model ARF.     

Effects of exogenous melatonin on myoglobinuric acute renal failure in the rats

Free oxygen radicals and nitric oxide (NO) play a crucial role in the pathogenesis of myoglobinuric acute renal failure (ARF). In this study, we aimed to investigate the effect of melatonin, a potent free radical scavenger, on the myoglobinuric ARF formed by injecting hypertonic glycerol intramuscularly (i.m.). The rats were randomly divided into 4 Groups. Rats in Group 1 were given saline and those in Groups 2, 3, and 4 were injected with glycerol (10 mL/kg) i.m. Concomitant and 24 hours after glycerol injection Group 3 (5 mg/kg) and Group 4 (10 mg/kg) were administrated melatonin intraperitoneally. Forty-eight hours after the glycerol injection, the blood and kidneys of the rats were taken under anesthesia. Kidney morphology and the levels of urea, creatinine and nitric oxide metabolites (NOx) in the plasma and the enzyme activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and the level of malondialdehyde (MDA) in the kidney were determined. In both groups of melatonin administration, there was no protective effect of melatonin. Moreover, melatonin significantly decreased the level of NO. As a result, we suggest that the decreasing effect of melatonin on NO, which is a strong vasodilatator, may further increase the renal ischemia in this model. Thus, melatonin may have worsening rather than beneficial effects on myoglobinuric ARF.     

Prolactin status in experimentally induced acute renal failure in the rat

Serum prolactin levels were elevated in male Sprague-Dawley rats with acute renal failure induced by glycerol administration. Specific prolactin binding to kidney membrane preparations was reduced in glycerol and antirat glomerular basement membrane serum-treated rats, after morphological and biochemical acute renal failure was evident. Extensive tubular damage after glycerol administration may account for loss of renal binding, since prolactin receptors are mainly tubular in localization. However, the predominant glomerulopathy, with less severe tubular lesions, after antirat glomerular basement membrane serum suggests that reduced renal prolactin binding in these animals is unlikely to be due to tubular destruction alone. Thus, alterations in prolactin status occur with development of experimentally induced acute renal failure and suggest altered renal responsiveness to prolactin in uraemia.     

L-Carnitine Ameliorates Glycerol-Induced Myoglobinuric Acute Renal Failure in Rats

There is increasing evidence indicating that oxidative stress plays an important role in the pathogenesis of rhabdomyolysis-induced myoglobinuric acute renal failure (ARF). During times of war and natural disasters, myoglobinuric ARF can assume epidemic proportions. Thus, early and effective renoprotective treatments are of utmost importance. It has been shown that L-carnitine, used as a safe and effective nutritional supplement for more than three decades, is effective in preventing renal injury in many renal injury models involving oxidative stress. The present study was performed to investigate the effects of L-carnitine in an experimental model of myoglobinuric ARF. Four groups of rats were employed in this study: group 1 served as a control; group 2 was given glycerol (10 mL/kg, i.m.); group 3 was given glycerol plus L-carnitine (100 mg/kg, i.p.), starting at the same time as the glycerol injection; group 4 was given glycerol plus L-carnitine (100 mg/kg, i.p.), starting 48h before the glycerol injection. After glycerol injections, the i.p. injections of L-carnitine were repeated every 24h for four days. Ninety-six hours after glycerol injections, blood samples and kidney tissues were taken from the anesthetized rats. Urea and creatinine levels in plasma, N-acetyl-beta-D-glucosaminidase activity in urine, and malondialdehyde levels and catalase enzyme activity in kidney tissue were determined. Histopathological changes and iron accumulation in the kidney tissue were evaluated. In this study, glycerol administration led to marked renal oxidative stress, as well as severe functional and morphological renal deterioration. L-carnitine, possibly via its antioxidant properties, ameliorates glycerol-induced myoglobinuric kidney injury.     

EFFECTS OF N-ACETYLCYSTEINE ON MYOGLOBINURIC-ACUTE RENAL FAILURE IN RATS

Oxygen metabolites play an important role in renal injury during myoglobinuric acute renal failure (ARF). This study was designed to determine the protective influence of N-acetylcysteine (NAC), a hydroxyl radical scavenger, and treatment in an experimental model of myoglobinuric-ARF induced by intramuscular injection of hypertonic glycerol in rats. The rats were randomly distributed into five groups: Group 0 (n = 10), was assigned to receive 2 mL saline (0,9%) intraperitoneally (ip); Group 1 (n = 10), NAC ip in a dose of 10 mg/100 g of body weight 30 min before the intramuscular (im) injection of 50% glycerol (10 mg/kg); Group 2 (n = 10), received saline 0,9% ip in a equivalent volume of NAC in Group 1 before the im injection of glycerol; Group 3 (n = 10), received NAC ip in a dose of 10 mg/100 g after im injection of glycerol; Group 4 (n = 10), saline 0,9% ip in a equivalent volume of NAC of the Group 3 after im administration of glycerol. After 24 h rats were sacrificed and kidney morphology and renal function were determined. A severe renal failure was produced by glycerol injection in the Groups 1, 2, 3, and 4, with significant tubular proximal necrosis and cast formation, and creatinine and urea concentrations were elevated in these groups without significant differences among groups, but Group 0 where the values were significantly lower. The results of this study suggests that ip administration of NAC in rats before or after glycerol injection do not confer protection against impairment of renal function under these conditions in this model of myoglobinuric-ARF.     

Melatonin reduces nitric oxide via increasing arginase in rhabdomyolysis-induced acute renal failure in rats

Melatonin, the chief secretory product of the pineal gland, is a direct free radical scavenger. In addition to a direct scavenging effect on nitric oxide (NO), its inhibitory effect on nitric oxide synthase (NOS) activity has been also reported. L-arginine is the substrate for both NOS and arginase. It has been suggested that there is a competition between arginase and NOS and that they control each other's level. NO plays a crucial role in the pathogenesis of myoglobinuric acute renal failure (ARF). In this study, the authors aimed to investigate the effect of melatonin on arginase activity, ornithine, and NO levels on the myoglobinuric ARF formed by intramuscular (i.m.) injection of hypertonic glycerol. Forty rats were randomly divided into four groups. Rats in SHAM were given saline, and those in groups ARF, ARF-M5, and ARF-M10 were injected with glycerol (10 mL/kg) i.m. Concomitant and 24 hours after glycerol injection for the ARF-M5 and ARF-M10 groups, melatonin--5 mg/kg and 10 mg/kg, respectively--was administrated intraperitoneally. Forty-eight hours after the glycerol injection, kidneys of the rats were taken under anesthesia. Arginase activity, ornithine, and NO levels in the kidney tissue were determined. Melatonin had an increasing effect on kidney tissue arginase activities and ornithine levels while decreasing NO concentration. It is possible that besides the direct scavenging effect, the stimulatory effect of melatonin on arginase activity may result in an inhibition of NOS activity and, finally, a decrease in the kidney NO level.     

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.     

L-arginine reduces tubular cell injury in acute post-ischaemic renal failure.

BACKGROUND: The pathophysiology of renal ischaemia, resulting in tubular cell injury and leading to acute renal failure (ARF), remains unclear. An ever-increasing number of investigations focus on a possible role of nitric oxide (NO) in regulating circulation during ARF. In this context, we investigated the influence of chronic stimulation or inhibition of NO synthesis, or both, on haemodynamic parameters, histology and plasma renin activity (PRA) after ischaemia-reperfusion injury of rat kidneys. METHODS: Experiments were performed on adult, male Wistar rats. Before induction of ARF, a group of animals was treated with a NO synthesis inhibitor (L-NAME) and another group was treated with a precursor of NO synthesis (L-arginine). The animals received those substances for 4 weeks. Control groups received the same amount of tap water for 4 or 8 weeks and were divided into groups with ARF (4 weeks--ARF group and 8 weeks ARF group) and a sham-operated group. Another group of rats was treated first with L-NAME and then with L-arginine in their drinking water, for 4 weeks for each of these two substances. All parameters were evaluated 24 h after the induction of ischaemic ARF or the sham operation. RESULTS: Our results show that such long-term stimulation of NO release by L-arginine improved renal haemodynamics in the ischaemic form of ARF. Renal blood flow (RBF) increased by 96% in the L-arginine-treated rats with ARF compared with the group with ARF alone. Inhibition of NO synthesis worsens renal haemodynamics after ARF. However, this aggravation can be reversed by L-arginine. The rate of water reabsorption was reduced in all groups with ARF, but this reduction was least in the group treated with L-arginine. The rate of Na+ reabsorption was reduced in all groups 24 h after renal ischaemia, but a significant decrease was observed after the inhibition of NO synthesis. Histological examination of the kidney specimens showed that morphological changes were least in the rats treated with L-arginine, when compared with all other groups with ARF. Nevertheless, the lesions were most prominent in the L-NAME+ARF group. In this group, the areas of corticomedullar necrosis were more widespread in comparison with other groups, especially the L-arginine group where only swelling of the proximal tubular cells was observed. Treatment with L-NAME was not accompanied by any significant alteration in the plasma concentration of angiotensin I (ANG I), while in the group treated with L-arginine ANG I had a tendency to decrease. CONCLUSIONS: Acute post-ischaemic renal failure may be alleviated by administering the NO substrate (L-arginine). NO acts cytoprotectively on tubular epithelial cells in ischaemia--reperfusion injury of rat kidney. Evidence of this comes from both histopathological findings and increased tubular water and sodium reabsorption. However, inhibition of NO synthesis (provoked by L-NAME) worsens renal haemodynamics and aggravates morphological changes after ARF. These aggravations can, however, be reversed by L-arginine.     

Effects of Exogenous Melatonin on Myoglobinuric Acute Renal Failure in the Rats

Free oxygen radicals and nitric oxide (NO) play a crucial role in the pathogenesis of myoglobinuric acute renal failure (ARF). In this study, we aimed to investigate the effect of melatonin, a potent free radical scavenger, on the myoglobinuric ARF formed by injecting hypertonic glycerol intramuscularly (im). The rats were randomly divided into 4 Groups. Rats in Group 1 were given saline and those in Groups 2, 3, and 4 were injected with glycerol (10 mL/kg) im. Concomitant and 24 hours after glycerol injection Group 3 (5 mg/kg) and Group 4 (10 mg/kg) were administrated melatonin intraperitoneally. Forty‐eight hours after the glycerol injection, the blood and kidneys of the rats were taken under anesthesia. Kidney morphology and the levels of urea, creatinine and nitric oxide metabolites (NO_x) in the plasma and the enzyme activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and the level of malondialdehyde (MDA) in the kidney were determined. In both groups of melatonin administration, there was no protective effect of melatonin. Moreover, melatonin significantly decreased the level of NO. As a result, we suggest that the decreasing effect of melatonin on NO, which is a strong vasodilatator, may further increase the renal ischemia in this model. Thus, melatonin may have worsening rather than beneficial effects on myoglobinuric ARF.     

α促黑素细胞激素对横纹肌溶解所致急性肾衰竭大鼠肾的保护作用

目的探讨α促黑素细胞激素（α—MSH）是否能减轻甘油诱导横纹肌溶解所致急性。肾衰竭（ARF）大鼠。肾组织中炎性反应和对。肾损害的保护作用。方法48只SD大鼠随机分4组：健康对照组：肌注生理盐水10ml／kg；ARF组;肌注50％甘油10ml／kg；α-MSH立即干预组：肌注50％甘油的同时腹腔注射α—MSH200μg／kg，12h后重复1次；α-MSH延迟干预组：肌注50％甘油6h后腹腔注射α—MSH200μg／kg，12h后重复1次。24h后处死大鼠，测Scr、BUN、肌酸激酶水平。。肾组织PAS染色光镜下行。肾小管坏死半定量评分。免疫组化ED-1染色半定量计数。实时定量PCR测。肾组织中单核细胞趋化因子（MCP）-1mRNA表达水平。结果与对照组相比，ARF组大鼠。肾组织内ED．1染色阳性细胞数（16．8±7．0比1．46＋1．24）、MCP-1的mRNA表达量（11．0±3．8比7．8±1．9）均显著增加（P均〈0．05）。α-MSH立即干预组ED-1染色阳性细胞数（9．5±8．2）和MCP．1的mRNA表达量（8．7±5．1）与ARF组相比均显著减少（P〈0．05）。α—MSH立即干预组Scr、BUN和。肾小管坏死评分均低于ARF组【分别为（152±76）比（333±60）μmol／L、（23．8±9．3）比（56．0±10．0）mmol／L和1．7±0．4比2．7±0．4，P均〈0．05]。而α-MSH延迟干预组与ARF组间各指标及各组间血IL．6和TNF—α差异均无统计学意义。结论甘油所致急性。肾衰竭大鼠。肾组织中巨噬细胞浸润及MCP-1表达增加，即刻注射α-MSH有一定的抑制。肾组织炎性反应、减轻。肾损害作用。     

Renal effects of mannitol in the early stage of glycerol-induced acute renal failure in the rat.

The effects of mannitol on the hemodynamics and excretory function of the kidney in control rats and in rats with acute renal failure (ARF), induced by glycerol, were studied using clearance, micropuncture and flowmeter techniques. In control animals, 20% mannitol significantly increased renal blood flow (RBF), urinary volume and sodium excretion and decreased urinary sodium concentration and fractional tubular sodium reabsorption. Glomerular filtration rate (GFR) and effective filtration pressure remained unchanged. 50% glycerol (10 ml/kg bw) was injected intramuscularly in other groups of rats to induce ARF. Functional impairment of the glycerol-treated animals consisted in a significant decrease in urinary sodium concentration, RBF, GFR and effective filtration pressure of superficial nephrons. Urea concentration in arterial plasma and urine volume increased significantly. Infusion of 20% mannitol into these animals led to a significant further decrease in GFR and net filtration pressure, but not in RBF. Urine volume increased to the same degree as in controls.