Cholestasis induced nephrotoxicity: The role of endogenous opioids

Aims Elevated levels of endogenous opioids play a pivotal role in several deleterious consequences of cholestasis Renal dysfunction occurs in cholestasis but its exact mechanism is still unknown In this study, we investigated the role of endogenous opioids in cholestasis induced nephrotoxicity Main methods Thirty-five rats were divided into five groups In groups 1 and 2 BDL rats received either daily subcutaneous 20 mg/kg of naltrexone or its vehicle, for 7 days after BDL In groups 3 and 4, BDL or Sham rats received no injections In group 5, normal rats received subcutaneous injections of 20 mg/kg/day of naltrexone for 7 days At the 7th clay, 24 h urine was collected to measure urinary N-acetyl-beta-D-glucosaminidase (NAG) as an early marker of renal tubular injury Kidney samples were then collected for light and electron microscopic studies. Key findings BDL significantly increased NAG activity compared to sham groups Naltrexone significantly reversed NAG activity to normal levels in BDL animals Naltrexone treatment in BDL animals also significantly reversed ALT and AST to their normal levels In light and electron microscopic studies, there were significant structural alterations in BDL samples, which were mostly prevented in naltrexone treated BDL animals. Significance Significant changes in urinary NAG activity and renal morphology of cholestatic rats were reversed by naltrexone treatment These results suggest a possible role for endogenous opioids in inducing cholestatic nephrotoxicity (C) 2010 Elsevier Inc All rights reserved