High‐dose sinomenine attenuates ischemia/reperfusion‐induced hepatic inflammation and oxidative stress in rats with diabetes mellitus

Abstract

Abstract Introduction Ischemia‐reperfusion (I/R) injury, resulting from blood flow interruption and its subsequent restoration, is a prevalent complication in liver surgery. The liver, as a crucial organ for carbohydrate and lipid metabolism, exhibits decreased tolerance to hepatic I/R in patients with diabetes mellitus (DM), resulting in a significant increase in hepatic dysfunction following surgery. This may be attributed to elevated oxidative stress and inflammation. Our prior research established sinomenine's (SIN) protective role against hepatic I/R injury. Nevertheless, the impact of SIN on hepatic I/R injury in DM rats remains unexplored. Objective and Methods This study aimed to investigate the therapeutic potential of SIN in hepatic I/R injury in DM rats and elucidate its mechanism. Diabetic and hepatic I/R injury models were established in rats through high‐fat/sugar diet, streptozotocin injection, and hepatic blood flow occlusion. Liver function, oxidative stress, inflammatory reaction, histopathology, and Nrf‐2/HO‐1 signaling pathway were evaluated by using UV spectrophotometry, biochemical assays, enzyme‐linked immunosorbent assay, hematoxylin‐eosin staining, and Western blot analysis. Results High‐dose SIN (300 mg/kg) significantly attenuated hepatic I/R injury in DM rats, reducing serum activities of ALT and AST, decreasing the AST/ALT ratio, enhancing tissue contents of SOD and GSH‐Px, suppressing the levels of TNF‐α and IL‐6, improving the liver histopathology, and activating Nrf‐2/HO‐1 signaling by promoting Nrf‐2 trans‐location from cytoplasm to nucleus. Low‐dose SIN (100 mg/kg) was ineffective. Conclusions This study demonstrates that high‐dose sinomenine's mitigates hepatic I/R‐induced inflammation and oxidative stress in diabetes mellitus (DM) rats via Nrf‐2/HO‐1 activation, suggesting its potential as a preventive strategy for hepatic I/R injury in DM patients.

Keywords

• hepatic ischemia reperfusion
• inflammation
• oxidative stress
• sinomenine