Investigating the role of endogenous opioids and K_ATP channels in glycerol‐induced acute renal failure

Abstract

The present study was designed to investigate the possible role of endogenous opioids and K(ATP) channels in glycerol-induced acute renal failure (ARF) in rats. 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 h of glycerol injection. The plasma creatinine, blood urea nitrogen, creatinine clearance, and histopathological studies were performed to assess the degree of renal injury. Naltrexone (2.5, 5.0 and 10.0 mg/kg s.c.), glibenclamide (5.0 and 10.0 mg/kg i.p.), and minoxidil (25 and 50 mg/kg) were employed to explore the role of endogenous opioids and K(ATP) channels in rhabdomyolysis-induced ARF. Pretreatment with naltrexone and glibenclamide attenuated hypertonic glycerol-induced renal dysfunction in a dose-dependent manner, suggesting the role of endogenous opioids and K(ATP) channels in the pathogenesis of myoglobuniric renal failure. However, the simultaneous pretreatment with naltrexone (10 mg/kg s.c.) and glibenclamide (10 mg/kg i.p.) did not enhance the reno-protective effects of individual drugs, suggesting that release of endogenous opioids and opening of K(ATP) channels constitute a single pathway in acute renal injury triggered by hypertonic glycerol-induced rhabdomyolysis. Furthermore, administration of minoxidil abolished the attenuating effects of naltrexone in glycerol-induced renal failure, suggesting that opening of K(ATP) channels is downstream to opioid receptor activation. It is concluded that hypertonic glycerol-induced rhabdomyolysis may involve release of endogenous opioids that in turn modulate K(ATP) channels to contribute in the pathogenesis of ARF.

Curcumin-Loaded Nanoparticles Protect Against Rhabdomyolysis-Induced Acute Kidney Injury

“…In the clinic, an increase in serum CPK levels is used to diagnose rhabdomyolysis, whereas elevated serum Cr and urea levels indicate kidney damage by rhabdomyolysis [2]. In this study, SD rats were intramuscularly injected with a single dose of 10 mg/kg glycerol as previously described [17, 18]. Glycerol-treated rats exhibited significantly elevated levels of serum CPK, Cr and urea compared with control animals.…”

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Experimental Evaluation of Furosemide and/or Tadalafil in Conventional and Nanoparticle Forms in Prevention of Chronic Renal Failure Induced in Rats

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