Morphine dependence protects rat kidney against ischaemia-reperfusion injury.
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. 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. 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. 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.
Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran. habibey.r@gmail.com
Rouhollah
R
Habibey
Hamidreza
H
Pazoki-Toroudi
D000818:Animals; D004334:Drug Administration Schedule; D007279:Injections, Subcutaneous; D019194:Ischemic Preconditioning / Q000379:methods; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology*; D008297:Male; D009020:Morphine / Q000008:administration & dosage; D009021:Morphine Dependence; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000502:physiology; D015427:Reperfusion Injury / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D011957:Receptors, Opioid; D009020:Morphine