Chelerythrine Attenuates Renal Ischemia/Reperfusion-induced Myocardial Injury by Activating CSE/H2S via PKC/NF-κB Pathway in Diabetic Rats.

Background/Aims: Chelerythrine (CHE), a benzophenanthridine alkaloid, is a potent, selective, and cell-permeable protein kinase C (PKC) inhibitor. The purpose of the present study was to evaluate the effect of [HE on myocardial recovery after renal ischemia/reperfusion (I/R)induced myocardial injury (RI/RMI) in a streptozocin (STZ)-induced diabetic rat model. Methods: Diabetes mellitus (DM) rats preconditioned with CHE and D, L-propargylglycine (PAG) were subjected to renal I/R. The extent of cardiac morphologic lesions and the biochemical markers of cardiorenal function and oxidative stress were detected utilizing hematoxylin-eosin staining, commercial kits, and enzyme-linked immunoassay, respectively. The expressions of cystathionine-y-lyase (CSE), PKC-alpha, PKC-beta(2), and nuclear factor-kappa B (NF - kappa B) in the rat myocardial tissue were measured utilizing western blotting. Results: Renal I/R treatment resulted in myocardial injury. CHE-preconditioning promoted the recovery from myocardial damage by ameliorating the biochemical parameters of myocardial injury, reducing oxidative stress, increasing the H2S level, up-regulating the expression of CSE, and down-regulating the expressions of PKC-a, PKC-beta(2), and NF-kappa B. Conclusion: These findings suggest that CHE-pretreatment may exert a protective effect on the myocardium against RI/RMI by activating endogenous CSE/H2S via PKC/NF-kappa B pathway in STZ-induced diabetic rats. Further studies are needed defining underlying mechanisms. (C) 2017 The Author(s) Published by S. Karger AG, Basel