Cholestasis induced nephrotoxicity: the role of endogenous opioids.
OBJECTIVE
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.


METHODS
Thirty-five rats were divided into five groups. In groups 1 and 2 BDL rats received either daily subcutaneous 20mg/kg of naltrexone or its vehicle, for 7days after BDL. In groups 3 and 4, BDL or Sham rats received no injections. In group 5, normal rats received subcutaneous injections of 20mg/kg/day of naltrexone for 7days. At the 7th day, 24h 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.


RESULTS
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.


CONCLUSIONS
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.
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.
Armin Farajzadeh
AF
Deroee
Behtash Ghazi
BG
Nezami
Shahram Ejtemaei
SE
Mehr
Rohollah
R
Hosseini
Amirali Hassanzadeh
AH
Salmasi
Saman Shafaat
SS
Talab
Issa
I
Jahanzad
Ahmad Reza
AR
Dehpour
D000118:Acetylglucosaminidase / Q000378:metabolism / Q000652:urine; D000701:Analgesics, Opioid / Q000378:metabolism*; D000818:Animals; D001663:Bilirubin / Q000097:blood; D002779:Cholestasis / Q000139:chemically induced / Q000150:complications*; D004789:Enzyme Activation / Q000187:drug effects; D007668:Kidney / Q000201:enzymology / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology; D008099:Liver / Q000187:drug effects; D008297:Male; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009271:Naltrexone; D000118:Acetylglucosaminidase; D001663:Bilirubin