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MORPHINE DEPENDENCE PROTECTS RAT KIDNEY AGAINST ISCHAEMIA–REPERFUSION INJURY
Author(s) -
Habibey Rouhollah,
PazokiToroudi Hamidreza
Publication year - 2008
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2008.04986.x
Subject(s) - morphine , creatinine , (+) naloxone , kidney , blood urea nitrogen , fractional excretion of sodium , medicine , ischemia , reperfusion injury , renal ischemia , opioid , anesthesia , pharmacology , endocrinology , receptor
SUMMARY1 Ischaemic preconditioning (IPC) protects the heart and kidneys against ischaemia–reperfusion (I/R) injury. It has been shown that opioid receptor activation can mimic cardiac IPC. In a kidney model of I/R, a single dose of morphine failed to mimic IPC. The aim of the present study was to determine the role of chronic morphine (dependence) in protection against renal I/R injury. 2 Male Wistar rats were treated with increasing doses of morphine (20–30 mg/kg per day, s.c., for 5 days) to develop morphine dependence (MD). Three weeks before the I/R procedure, the right kidney was removed. Ischaemia–reperfusion injury was induced by clamping the left renal artery for 45 min, followed by 24 h reperfusion. Some MD rats were pretreated with naloxone (5 mg/kg, s.c.). Twenty‐four hours later, creatinine and sodium concentrations were measured in serum and urine, then creatinine clearance (CCr) and the fractional excretion of sodium (FE Na ) were calculated. Blood urea nitrogen (BUN) was measured only in serum samples. Kidneys were also assessed histologically for evidence of tissue injury. 3 In the present study, MD decreased tissue injury (histological score), serum creatinine and BUN levels, increased CCr and decreased FE Na after I/R. Pretreatment with naloxone attenuated the protective effects of MD. Morphine dependence did not have any significant effect on urine volume. 4 In conclusion, it seems that morphine dependence protects the kidney against I/R injury via opioid receptor‐dependent pathways. Further studies are required to clearly determine the mechanisms involved.