DIFFERENT EFFECTS OF GLUCOCORTICOIDS; DEXAMETHASONE AND NSAIDS; INDOMETHACIN ON HEPATIC AND RENAL INJURY FOLLOWING NORMOTHERMIC HEPATIC ISCHEMIA-REPERFUSION IN RATS

Purpose: Hepatic ischemia reperfusion (IR) injury is a pathophysiologic process that leads to oxidative stress and acute inflammatory responses. Understanding the mechanisms explaining this inflammation is fundamental to developing therapeutic strategies. Therefore, the main purpose of this study was to evaluate the effect of two different anti-inflammatory agents as glucocorticoids; dexamethasone (DEX) and NSAIDs; indomethacin (IND) against hepatic and renal damages caused by normothermic hepatic IR injury.

Materials/Methods: Sprague-Dawley rats were randomly divided into four groups: sham control group; hepatic IR group; hepatic IR+DEX; hepatic IR+IND. DEX (10 mg/kg, ip) and IND (5 mg/kg, ip) were administered 30 min prior to normothermic ischemia.

Results: DEX significantly attenuated the IR induced elevations in the serum level of transaminases, urea, creatinine, tumor necrosis factor α (TNF-α) and nitric oxide (NO) levels while IND pretreatment aggravated these parameters as compared with IR group. DEX and IND pretreatment down-regulated the IR induced cyclo-oxygenase-2 (COX-2) over-expression. DEX also significantly compensated deficits in total hepatic and renal antioxidant capacities (TAC) and suppressed malondialdehyde (MDA) levels observed with hepatic IR that is aggravated with IND treatment. Inflammatory cells infiltration, cytoplasmic vaculation and apoptosis, detected by histopathological examination of hepatic and renal tissues, were markedly ameliorated by pre-ischemic DEX treatment not IND pretreatment.

Conclusion: DEX prevented ischemic hepatic and renal damages, but IND aggravated these damages in hepatic IR injury so DEX can be considered a potential therapeutic agent to protect against the major clinical challenge of liver injury resulting from IR.