Protective role of Zinc glycine in LPS-induced acute kidney injury in geese: Inhibition of oxidative stress and ferroptosis through Nrf2/GPX4 signaling.

Abstract

Acute kidney injury (AKI) induced by lipopolysaccharide (LPS) is a critical pathological condition associated with inflammation, oxidative stress, and ferroptosis. Zinc glycine (Zn_Gly), a novel organic zinc complex, has demonstrated anti-inflammatory, antioxidant, and anticancer properties. To investigate the protective effects of Zn_Gly on LPS-induced AKI in geese, 180 one-day-old geese were randomly divided into three groups: control, LPS, and LPS+Zn_Gly (80 mg/kg). Dietary supplementation with Zn_Gly significantly reduced LPS and ROS production in geese. Moreover, serum creatinine, urea, uric acid, and LDH activity were markedly decreased following Zn_Gly supplementation in AKI-affected geese. Histopathological analysis showed that Zn_Gly markedly attenuated glomerular fragmentation, Bowman's capsule enlargement, hemorrhage, and leukocyte infiltration compared with the LPS group. Renal iron content was also significantly reduced in the LPS+Zn_Gly group. Furthermore, Zn_Gly supplementation suppressed renal inflammatory cytokines (IL-1β, IL-6, and TNF-α) while enhancing IL-10 production. At the molecular level, Zn_Gly significantly upregulated the expression of Nrf2, HO-1, NQO1, GCLC, GCLM, GPX4, SLC7A11, and FTH1, while downregulating Keap1 and PTGS2 in LPS-induced AKI. Western blot analysis confirmed the increased protein expression of Nrf2, HO-1, GCLC, GPX4, SLC7A11, and FTH1, and the decreased expression of Keap1 and PTGS2. Immunofluorescence further demonstrated enhanced renal expression of Nrf2 and GPX4 in LPS-induced AKI. Collectively, these findings suggest that Zn_Gly alleviates LPS-induced AKI by attenuating oxidative stress and ferroptosis through activation of the Nrf2/GPX4 pathway, thereby contributing to improved renal health in geese.