Effects of Losartan on Glycerol-induced Myoglobinuric Acute Renal Failure in Rats

Abstract

SummaryMyoglobinuric acute renal failure (mARF) is an uremic syndrome which develops due to damage of skeletal muscle. It was demonstrated that free radicals and nitric oxide (NO) play an important role in pathogenesis of mARF. Our aim was to investigate the effect of losartan, a drug known for its antioxidant effect, on mARF. In our study, a total of 34 male Spraque Dawley rats were divided into four groups. 1 st and 2 nd groups were injected with saline, 3 rd and 4 th groups were injected with intramuscular glycerol. One and 24 hours later, 1 st and 3 rd groups received saline orally and 2 nd and 4 th groups have taken 10 mg/kg losartan. Urine was collected; the blood samples and kidneys of the rats were taken under the anesthesia. The levels of NO, arginine, asymmetric dimethylarginine (ADMA), glutathione (GSH) and malondialdehyde (MDA) were determined, renal functions and histopathological changes examined. In our study, we found that levels of urea, creatinine, and potassium, in serum samples and MDA and ADMA in renal tissue were increased in 3 rd group when it's compared with the 1 st group. Levels of sodium, arginine in serum samples and arginine in renal tissue were reduced 3 rd group when compared with the 1 st group. When 3 rd and 4 th groups were compared, serum creatinine was higher in the latter group whereas ADMA level in renal tissue was lower in the same group. We think that there is no positive effect of losartan on the pathogenesis of mARF.

A study on the effect of cimetidine and l-carnitine on myoglobinuric acute kidney injury in male rats

“…In accordance with our results, Singh et al and Kaya et al, reported an increase in blood urea and creatinine levels in ARF [23,24]. Also the GFR was found to be decreased [25,26].…”

“…This was in accordance with studies conducted by Chander et al [37] and Aydogdu et al [6]. However, no significant decrease in GSH level was noted by Kaya et al studying on the same animal model [24]. GSH acts as a radical scavenger by itself, and as a detoxicant by eliminating different electrophilic toxic compounds [38].…”

“…However, contrary to our study, many studies on glycerol induced myoglobinuric ARF showed a decrease in serum Na levels [7,24,31]. Glycerol-induced ARF and the associated increase in the systolic blood pressure may be attributed to increased angiotensin II (Ang II) or thomboxane A2 (TXA2), or may be due to vasoconstriction induced by down-regulation of peroxisome proliferator-activated receptor gamma (PPAR-g) expression/activity, probably via an increased free radical generation [32].…”

“…Also the GFR was found to be decreased [25,26]. Kaya et al reported a significant increase in serum K level [24]. The increase in blood pressure was also demonstrated by studying the same animal model [27].…”

“…Other studies showed no significant difference in NO levels [24]. Gö k found a decrease in renal NO levels studying the same animal model [41].…”