Protective Effects the Akt Activator SC79 in Hepatic Ischemia-Reperfusion Injury
Hui Zhou, Ying Yu, Jinna Zhang, Yunfang Zhang, Qi Luan, Gongming Wang
Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China (mainland)
Med Sci Monit 2018; 24: LBR4346-4354
DOI: 10.12659/MSM.911178
Available online: 2018-06-24
Published: 2018-06-24

BACKGROUND:
SC79 has been reported to protect against experimental ischemia-elicited neuronal death and brain injury and to protect myocardiocytes from hypoxia/reoxygenation (H/R) injury. Here, we investigated the effects of SC79 in primary hepatocytes in vitro and in rat liver in vivo following hypoxia-reoxygenation (H/R) and hepatic I/R injury.
MATERIAL AND METHODS:
The livers of Sprague-Dawley rats were subjected to 45 min of ischemia followed by 2–24 h of reperfusion. The primary hepatocytes were subjected to hypoxia for 6 h and for 2–24 h. The hepatocytes cells or the hepatic I/R injury model livers were treated with SC79 or/and LY294002 at different times and concentrations. The serum ALT, AST, histologic examination, cellular viability, and cell apoptosis were assessed. The levels of phospho-Akt, Bad, Bim, Bax, Bcl-2, and Bcl-XL were determined by Western blot analysis.
RESULTS:
SC79 improved viability and inhibited apoptosis in hepatocytes following H/R. SC79 decreased serum AST and ALT, markedly improved pathology, and decreased cell apoptosis in livers following I/R. In addition, SC79 promoted the expression of phospho-Akt, Bcl-2, and Bcl-XL, and decreased the expression of Bid, Bax, and Bim. PI3K inhibitor (LY294002) pre-treatment completely abolished the above-mentioned effects of SC79.
CONCLUSIONS:
The protective role of SC79 against H/R of hepatocytes or hepatic I/R injury is related to activation of phosphorylation of Akt, resulting in the decrease of pro-apoptotic protein of Bim, Bax, and Bad, and increase of the anti-apoptotic protein Bcl-2 and Bcl-xL induced by cell H/R and hepatic I/R injury.
Keywords: Adjuvants, Anesthesia, Liver Failure, Acute, Oncogene Protein v-akt