Cilostazol Attenuates Murine Hepatic Ischemia and Reperfusion Injury via Heme Oxygenase-Dependent Activation of Mitochondrial Biogenesis.

Cilostazol Attenuates Murine Hepatic Ischemia and Reperfusion Injury via Heme Oxygenase-Dependent Activation of Mitochondrial Biogenesis. Am J Physiol Gastrointest Liver Physiol. 2015 May 7;:ajpgi.00307.2014 Authors: Joe Y, Zheng M, Kim HJ, Uddin MJ, Kim SK, Chen Y, Park J, Cho GJ, Ryter SW, Chung HT Abstract Hepatic ischemia/reperfusion (I/R) can cause hepatocellular injury associated with the inflammatory response and mitochondrial dysfunction. We studied the protective effects of the phosphodiesterase inhibitor cilostazol in hepatic I/R, and the roles of mitochondria, and the Nrf2/ heme oxygenase-1 (HO-1) system. Wild type, Hmox1(-/-) or Nrf2(-/-) mice were subjected to hepatic I/R in the absence or presence of cilostazol followed by measurements of liver injury. HepG2 cells were subjected to cilostazol with the HO-1 inhibitor ZnPP, or Nrf2 specific siRNA, followed by assessment of mitochondrial biogenesis. Preconditioning with cilostazol prior to hepatic I/R protected against hepatocellular injury, and mitochondrial dysfunction. Cilostazol reduced the serum levels of ALT, TNF-α and liver myeloperoxidase content relative to control I/R-treated mice. In cultured HepG2 cells, cilostazol increased the expression of HO-1 and markers of mitochondrial biogenesis, PGC-1α, NRF-1 and TFAM, induced the mitochondrial proteins COX III, and COX IV, and increased mtDNA and mitochondria content. Pre-treatment of HepG2 cells with ZnPP inhibited...
Source: Am J Physiol Gastroi... - Category: Gastroenterology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research