Objective To explore the role and mechanism of tannic acid in renal ischemia-reperfusion injury (IRI) in mice.

Methods Male C57BL/6J mice were randomly divided into sham operation group (Sham group), blank control group (Sham+TA group), experimental group (IRI group) and treatment group (IRI+TA group), with 20 mice in each group. The survival of mice after renal IRI was observed 48 h after surgery. Serum and renal tissue samples were collected from mice 24 h after IRI (5 mice per group), and the levels of blood urea nitrogen and serum creatinine were detected. The levels of inflammatory factors and ferroptosis-related indicators in renal tissue were detected. The pathological damage of renal tissue was assessed. The protein expression levels of glutathione peroxidase 4 (GPX4) and acyl-CoA synthetase long-chain family 4 (ACSL4) in renal tissue were detected. Molecular docking software was used to explore the binding activity of tannic acid with nuclear factor E2-related factor 2 (Nrf2) and to verify the expression of Nrf2 and heme oxygenase-1 (HO-1).

Results Compared with the IRI group, the postoperative survival rate of mice in the IRI+TA group was higher (0 vs. 60%), the levels of serum creatinine and blood urea nitrogen were decreased, the levels of interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α in renal tissue were decreased, the renal tissue injury was improved, the levels of malondialdehyde and ferrous ions in renal tissue were reduced, the level of glutathione was increased, the expression of GPX4 was increased, and the expression of ACSL4 was decreased (all P<0.05). Tannic acid may form a suitable spatial complement with Nrf2, with a binding energy of −8.7 kcal/mol, indicating a strong binding ability of tannic acid with Nrf2. The protein levels of Nrf2 and HO-1 in the renal tissue of mice in the IRI+TA group were upregulated.

Conclusions Tannic acid may bind to Nrf2 protein, activate the Nrf2/HO-1 pathway to inhibit ferroptosis, and alleviate renal IRI in mice.