Honokiol reduces oxidative stress by activating the SIRT3-MnSOD2 pathway to alleviate hypertriglyceridemia-induced acute pancreatitis in rats

Abstract

To determine how honokiol affects the sirtuin-3 (SIRT3)-MnSOD2 pathway and oxidative stress in rats with hypertriglyceridemia-induced acute pancreatitis (HTGP). Thirty 4-week-old male SD rats were randomly divided into two groups for normal feeding and high-fat feeding for 4 weeks, after which the rats with normal feeding were randomized into control group and acute pancreatitis (AP) group (n=6), and those with high-fat feeding were divided into hypertriglyceridemia group, HTGP group, and honokiol treatment group (n=6). In AP, HTGP, and honokiol groups, AP models were established by intraperitoneal injection of cerulean; in honokiol group, the rats received an intraperitoneal injection of 5 mg/kg honokiol 15 min after cerulean injection. Serum TG, IL-6, and TNF-α levels were measured 24 h after the treatments, and pathological changes in the pancreas were observed with HE staining; The levels of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione peroxidase (GSH) were measured, and SIRT3 and manganese superoxide dismutase (MnSOD2) expressions were detected using Western blotting and immunohistochemistry. Transmission electron microscopy was used to examine the ultrastructure of pancreatic acinar cells and mitochondria. Compared with the those with normal feeding, the rats with high-fat feeding had significantly elevated serum TG level (P < 0.05). The rat models of AP showed significantly increased serum levels of IL-6, TNF-α, and MDA and decreased GSH level and expressions of SIRT3 and MnSOD2, with obvious edema and inflammatory cell infiltration and enhanced ROS fluorescence intensity in the pancreas and ultrastructural damages of the acinar cells and mitochondria. In rats with HTGP, honokiol treatment significantly decreased serum levels of IL-6, TNF-α, and MDA, increased GSH level and SIRT3 and MnSOD2 expressions, reduced ROS production, and alleviated ultrastructural damage of the acinar cells and mitochondria in the pancreas. Honokiol reduce oxidative stress and alleviates pancreatic injuries in HTGP rats possibly by activating the SIRT3-MnSOD2 pathway.