Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Morphine dependence protects rat kidney against ischaemia-reperfusion injury. 1856 96

Morphine treatment for 5 days protects heart against ischemia-reperfusion (IR) injury. This study evaluated the involvement of nitric oxide (NO) in morphine-induced renal protection. Three weeks after right nephrectomy, increasing doses of morphine were administered (20-30 mg kg(-1)day(-1), 5 days) to develop dependence in rats. The left kidney underwent 45-min ischemia and 24-h reperfusion. Some rats were pretreated with naloxone (5 mg kg(-1)) or L-NAME (20 mg kg(-1)). In one group, IR was induced 24h after the last dose of morphine during the withdrawal period. Plasma nitrite/nitrate levels and serum creatinine and BUN were measured. Creatinine clearance and fractional excretion of sodium (FE(Na)) were calculated. Myeloperoxidase (MPO) activity, malondialdehyde (MDA) level, and inducible NO synthase (iNOS) expression were determined and histopathology was studied in the left kidney. IR increased serum creatinine and BUN, plasma NO (p<0.01), FE(Na), iNOS expression (p<0.001), MPO activity, MDA level, and tissue damage and decreased creatinine clearance. Morphine decreased plasma NO (p<0.05 vs IR), serum creatinine and BUN (p<0.01), FE(Na), MPO activity, MDA level, iNOS expression, and tissue damage (p<0.05), but increased creatinine clearance (p<0.05). Pretreatment with naloxone significantly increased NO production and iNOS expression in morphine-treated rats after IR (p<0.01 vs morphine dependence+IR). Pretreatment with L-NAME in morphine-treated rats decreased NO production (10.7+/-1.9, p<0.01 vs morphine dependence+IR) but could not change iNOS expression after IR. Both naloxone and L-NAME significantly abolished the protective effects of morphine dependence on functional and histological factors. The protective effect of morphine dependence on serum creatinine, BUN, FE(Na), and creatinine clearance persisted during the withdrawal period, whereas iNOS expression decreased. NO production was not decreased during the withdrawal period (p>0.1 vs morphine dependence+IR group). Morphine dependence provided renal protection in the acute phase and during withdrawal. Excessive increase or decrease in NO production abolished the effects of morphine, which suggested a role for balanced NO production and iNOS expression.
 ...
PMID:Nitric oxide and renal protection in morphine-dependent rats. 2060 Aug 30