Protective effect of urolithin A pretreatment in a rat model of hepatic ischemia-reperfusion injury

Objective To investigate the protective effect of urolithin A(Uro-A) against hepatic ischemia-reperfusion injury(HIRI) in rats.Methods A total of 40 Sprague-Dawley rats were randomly divided into sham-operation group,model group,low-dose Uro-A(1 mg/kg) group,and high-dose Uro-A(3 mg/kg) group,with 10 rats in each group.Before modeling,the rats in the low-and high-dose Uro-A groups were given the drug by gavage once a day for 5 consecutive days.The model was established after anesthesia,and the serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and lactate dehydrogenase(LDH) were measured at 6 hours after the recovery of blood flow.ELISA was used to measure the content of superoxide dismutase(SOD),malondialdehyde(MDA),catalase(CAT),interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α) in the liver,and liver pathological injury and hepatocyte apoptosis were evaluated.Western blot was used to measure the expression of the endoplasmic reticulum chaperone glucose-regulated protein 78(GRP78),the downstream transcription factor CHOP,and the apoptosis protein caspase-12 in the liver.A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results Compared with the model group,the high-dose Uro-A group had significantly lower levels of ALT,AST,LDH,MDA,CAT,IL-1β,IL-6,TNF-α,CHOP,GRP78,and caspase-12 and apoptosis rate and a significantly higher content of SOD(all P<0.05).The model group had severe damage of liver structure,with a positive rate of 90%,while the high-dose Uro-A group had intact liver structure without obvious tissue proliferation or inflammatory cell proliferation,with a negative rate of 80%.Compared with the high-dose Uro-A group,the low-dose Uro-A group had significant increases in the levels of ALT,AST,and LDH and apoptosis rate(all P<0.05).Conclusion Uro-A pretreatment can alleviate liver ischemia-reperfusion injury in rats and reduce oxidative damage and the release of inflammatory factors,possibly by inhibiting the endoplasmic reticulum stress pathways and reducing hepatocyte apoptosis.