Gülizar Atmaca

PROTECTIVE EFFECTS OF l-CARNITINE ON MYOGLOBINURIC ACUTE RENAL FAILURE IN RATS

1 Muscle injury (rhabdomyolysis) is one of the causes of acute renal failure (ARF). Iron, free radicals and nitric oxide (NO) play a critical role in the pathogenesis of glycerol‐induced myoglobinuric ARF. l‐Carnitine is an anti‐oxidant and prevents the accumulation of end‐products of lipid peroxidation. Therefore, the aim of the present study was to investigate the effects of l‐carnitine on myoglobinuric ARF induced by intramuscular (i.m.) hypertonic glycerol injection. 2 Sprague‐Dawley rats were divided into three groups. Rats in group 1 (n = 8) were given saline, whereas those in groups 2 (n = 10) and 3 (n = 10) were injected with glycerol (10 mL/kg, i.m.). Concomitant with and 24 h after glycerol injection, l‐carnitine (200 mg/kg, i.p.) was administered to group 3 rats. Forty‐eight hours after glycerol injection, blood samples and kidney tissues were taken from anaesthetised rats. 3 Plasma creatine kinase (CK) activity, urea, creatinine and NO levels, as well as kidney tissue superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) enzyme activity and malondialdehyde (MDA) and glutathione (GSH) levels, were determined. In the kidney tissue, histopathological changes and iron accumulation in the tubular epithelium were also investigated. 4 Glycerol treatment caused severe ARF: a marked renal oxidative stress, significantly increased CK activity, urea and creatinine levels and decreased plasma NO levels. Histopathological findings in group 2 rats confirmed that there was renal impairment by cast formation and tubular necrosis and a marked increase in iron accumulation in the tubular epithelium. All these factors were significantly improved by l‐carnitine supplementation. 5 These results may indicate that l‐carnitine treatment protects against functional, biochemical and morphological damage and iron accumulation in glycerol‐induced myoglobinuric ARF in rats. In this model, the protective effect of l‐carnitine treatment may provide a new insight into the treatment of rhabdomyolysis‐related ARF.

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 intramusculer hypertonic glycerol injection.

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 others 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 (im) 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) im. 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.

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 (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.