Abstract

The current study was designed to address the question of whether inducing heat shock proteins (HSPs) by herbimycin A might have a renoprotective effect in ischemic reperfusion (I/R) injury to rat kidney. The study was conducted on 56 male Wistar albino rats that were divided into three groups: Group I was subdivided into group Ia in which sham operation was done, Group Ib in which sham operation was done also received KNK437 (an inhibitor of heat HSP) prior to sham operation as well as after sham operation and Group Ic that received herbimycin A (1 h prior to sham operation as well as 1 and 24 h after sham operation, group II was subdivided into Group IIa, in which I/R to the kidney was induced, and group IIb, in which I/R was induced and also received KNK437 prior to induction of I/R as well as after induction of I/R; Group III consisted of rats with I/R that received herbimycin A without KNK437 (Group IIIa) or with KNK437 (Group IIIb) prior to induction of I/R as well as after the induction of I/R to the kidney. Administration of herbimycin A resulted in a significant renoprotective effect assessed histologically and biochemically, where there was a significant decrease in serum urea nitrogen as well as in creatinine concentration in herbimycin-treated rats as compared to non-treated rats. Herbimycin also resulted in antiapoptotic effect evidenced by a significant decrease in renal caspase-3 activity, which is possibly mediated by a significant decrease in measured renal mitogen activated protein kinase (MAPK-p38). These renoprotective actions are mostly mediated by herbimycin-induced renal HSP70, since the protective effect of the drug was markedly attenuated by the HSP inhibitor, KNK437.

Key words: Heat shock protein, herbimycin, ischemia reperfusion injury, mitogen activated protein kinase.