Fucoidan Prevents Paraquat‐Induced Hepatic Injury by Attenuating Oxidative and Inflammatory Stress: An In Vivo and In Vitro Approach

Paraquat (PQ) is extremely toxic to humans and leads to hepatic inflammation. Fucoidan (FCN) regulates the progression of oxidative damage and inflammation. However, whether FCN mitigates PQ-induced hepatic damage remains undiscovered. This study aimed to elucidate the protective effects of FCN against PQ-induced hepatic injury both in vivo and vitro. Mice in PQ group were injected with PQ, MIHA cells in PQ group were exposed to PQ for 24 h, for the establishment of hepatic injury models. Hepatic injuries were assayed by serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST), liver histology, and myeloperoxidase (MPO) activity. Hepatic oxidative stress was assayed by malondialdehyde (MDA), superoxide dismutase (SOD), Heme oxygenase-1 (HO-1), quinone oxidoreductase-1 (NQO-1), kelch-like ECH-associated protein 1 (Keap-1), and nuclear factor erythroid-2-related factor 2 (Nrf2). Hepatic inflammation was assayed by nucleotide-binding domain and leucine-rich repeat containing protein 3 (NLRP3), Caspase-1, interferon (IL)-18, IL-6, IL-4, IL-10, tumor necrosis factor (TNF)-α, inducible isoform of Nitric Oxide Synthase (iNOS), and nuclear factor kappa-B (NF-κB) p-p65. In mice, pre-/post- treatment of FCN mitigated PQ-induced weight loss and higher liver/weight ratio, hepatic injury (increased serum ALT/AST concentrations, and MPO activity), oxidative stress (increased MDA content and Keap-1 protein level, impaired SOD activity, mRNA expressions of Nrf2, SOD1/2, HO-1 and NQO-1, protein expressions of Nrf2 and HO-1), hepatic inflammation (increased mRNA expressions of NLRP3, Caspase-1, IL-6, TNF-α, and IL-18, serum IL-6 and TNF-α contents, protein expression of p-p65), and hepatic mitochondrial dysfunction (increased mRNA level of iNOS). Meanwhile, in MIHA cells, FCN dose-dependently mitigated PQ-induced oxidative stress (increased protein expression of Keap-1, decreased mRNA expressions of Nrf2, SOD1/2, HO-1 and NQO-1, Nrf2 and HO-1 protein expressions), and inflammation (increased p-p65 protein expression, IL-6, TNF-α, and IL-18 mRNA expressions and decreased IL-10 and IL-4 mRNA expressions). FCN prevents PQ-induced hepatic injury by attenuating oxidative stress and inflammation via activating Nrf2/Keap-l signaling in vivo and in vitro.