With the widespread application of rare earth elements (REEs) in environment safety, food and medicine, they accumulate in the ecosystem and different human organs where REEs exert certain biological effects. Low dose REEs are proved to perform antioxidant effects, while high concentration can cause oxidative stress. However, scant information about rational doses and underlying mechanism of REEs as oxidants/antioxidants were illustrated. To elucidate these problems, here we performed a study that the ICR mice were received 0.1, 0.2, 1.0, 2.0 and 20.0 mg/kg lanthanum nitrate (La(NO3)3) by gavage for 30 days, and then were given 12 mL/kg ethanol once to undergo acute ethanol-induced oxidative stress. The antioxidant enzymes, antioxidants, peroxides and related proteins in Keap 1/Nrf2/p62 signaling pathway were measured. The results showed that La(NO3)3 inhibited hepatic morphological alternations by histopathological examination. Meanwhile, elevated superoxide dismutase (SOD) and glutathione (GSH), coupled with decreased alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA) and protein carbonyl (PC) were observed in serum and liver tissues of mice by enzyme-linked immunosorbent assay test. Furthermore, western blot analysis demonstrated that oxidative stress was alleviated due to enhanced NF-E2-related factor 2 (Nrf2) and phosphorylated p62 expressions as well as lower Kelch-like ECH-associated protein-1 (Keap 1), followed by the activation of heme oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO-1) and glutamate cysteine ligase, catalytic (GCLC) proteins. Our findings clearly highlighted that La(NO3)3 could restore the redox homeostasis disrupted by ethanol through provoking Keap 1/Nrf2/p62 signaling pathway, and the optimal dosages were 1.0 and 2.0 mg/kg.
Keywords: Acute ethanol-induced oxidative stress; Antioxidant effect; Keap 1/Nrf2/p62 pathway; Lanthanum nitrate; Rare earth elements.
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