Effects of alpha-melanocyte stimulating hormone on the expression of intercellular adhesion molecule-1 and renal function in acute ischemic renal failure in rats

Jo, Sang Kyung; Yoon, Jong Woo; Cha, Dae Ryong; Cho, Won Yong; Kim, Hyoung Kyu; Won, Nam Hee; Yoon, Soo Young; Chang, Kyung Hyun

Abstract

BACKGROUND
Acute renal failure is a reversible process in majority of cases but mechanisms of renal injury or recovery are poorly understood. Recently neutrophil infiltration is reported to potentiate inflammatory and cytotoxic cascade in ischemic renal injury and alpha-melanocyte stimulating hormone has been reported to have a potent anti-inflammatory properties in a variety of animal models. We examined the beneficial effects of alpha-MSH in acute ischemic renal injury in rats and tried to clarify its action mechanism.
METHODS
After unilateral nephrectomy, renal artery of contralateral kidney was clamped for 40 minutes and reperfused in female Sprague-Dawley rats. alpha-MSH (50(mu)g) and vehicle was injected intraperitoneally immediately after and 6, 24 hours after reperfusion. Biochemical, histological data, ICAM-1 mRNA, protein expressions and polymorphonuclear cell infiltration were examined.
RESULTS
alpha-MSH significantly attenuated the renal injury, measured by plasma BUN and creatinine level and also the degree of severity of histological injury (BUN 125.2+/-14.6 mg/dL : 46+/-19.6 mg/dL (p=0.004), creatinine 3.65+/-0.81 mg/dL : 1.47+/-0.5 mg/dL (p=0.005) at 24 hours after reperfusion, BUN 88+/-12.5 mg/dL : 25.5+/-15.8mg/dl (p=0.002), creatinine 2.76+/-0.5 mg/dL : 0.93+/-0.2 mg/dL (p=0.002) at 72 hours after reperfusion and 5.4+/-1.94/ 2.6+/-0.77 (p=0.006) at 24 hours after reperfusion in histilogical grading system). In the alpha-MSH treated groups, ICAM-1 mRNA expression decreased significantly compared to the vehicle treated ischemic group in 72 hours after reperfusion (0.49+/-0.01/0.31+/-0.2, p<0.008). ICAM-1 protein expression also decreased in alpha-MSH treated group, but it was not statistically significant. Polymorphonuclear cell infiltration showed a significant decrease in the alpha-MSH treated group at 24 hours after reperfusion (5.05+/-1.8/1.59+/-0.4, p=0.009).
CONCLUSION
alpha-MSH attenuates ischemic renal injury by inhibiting the expression of ICAM-1 and subsequent polymorphonuclear cell infiltration. These results provide a rationale of alpha-MSH as a potential therapeutic drug in acute renal failure.