Resveratrol modulates Toxoplasma gondii infection induced liver injury by intervening in the HMGB1/TLR4/NF-κB signaling pathway

• Published in: European journal of pharmacology Vol. 910; p. 174497
• Main Authors: Lu, Jing-Mei, Jin, Guang-Nan, Lu, Yu-Nan, Zhao, Xu-Dong, Lan, Hui-Wen, Mu, Shuai-Ru, Shen, Xin-Yu, Xu, Guang-Hua, Jin, Cheng-Hua, Ma, Juan, Jin, Xuejun, Xu, Xiang, Piao, Lian-Xun
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05.11.2021
• Subjects: Animals; Cell Line; Disease Models, Animal; Female; Hepatitis, Animal - immunology; Hepatitis, Animal - parasitology; Hepatitis, Animal - pathology; Hepatitis, Animal - prevention & control; Hepatocytes - drug effects; Hepatocytes - immunology; Hepatocytes - pathology; HMGB1 Protein - metabolism; HMGB1/TLR4/NF-κB; Humans; Inflammation; Liver - cytology; Liver - drug effects; Liver - immunology; Liver - pathology; Liver injury; Mice; NF-kappa B - metabolism; Resveratrol; Resveratrol - pharmacology; Resveratrol - therapeutic use; Signal Transduction - drug effects; Signal Transduction - immunology; Toll-Like Receptor 4 - metabolism; Toxoplasma gondii; Toxoplasmosis - complications; Toxoplasmosis - drug therapy; Toxoplasmosis - immunology; Toxoplasmosis - parasitology; Inflammation; Toxoplasma gondii; HMGB1/TLR4/NF-κB; Resveratrol; Liver injury
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2021.174497

Toxoplasma gondii (T. gondii) is an obligate intracellular parasite that can cause liver diseases in the host, including hepatitis and hepatomegaly. High mobility group box 1 (HMGB1) is the main inflammatory mediator causing cell injury or necrosis. HMGB1 binds to toll like receptor 4 (TLR4), then activates the nuclear factor-κB (NF-κB) signaling pathway, which promotes the release of inflammatory factors. Our previous studies showed that HMGB1 mediated TLR4/NF-κB signaling pathway plays an important role in liver injury induced by T. gondii infection. Resveratrol (RSV) is a small polyphenol, which has anti-inflammatory, anti-cancer, anti-T. gondii effect. However, the effect of RSV on liver injury caused by T. gondii infection is unclear. This study used the RH strain tachyzoites of T. gondii to infect murine liver line, NCTC-1469 cells to establish an in vitro model and acute infection of mice for the in vivo model to explore the protective effect of RSV on liver injury induced by T. gondii infection. The results showed that RSV inhibited the proliferation of T. gondii in the liver, reduced the alanine aminotransferase/aspartate aminotransferase levels and pathological liver damage. Additionally, RSV inhibited the production of tumor necrosis factor-α, inducible nitric oxide synthase and HMGB1 by interfering with the TLR4/NF-κB signaling pathway. These results indicate that RSV can protect liver injury caused by T. gondii infection by intervening in the HMGB1/TLR4/NF-κB signaling pathway. This study will provide a theoretical basis for RSV treatment of T. gondii infection induced liver injury. [Display omitted] •Resveratrol has a protective effect on liver injury induced by T. gondii infection.•Resveratrol inhibits the production of HMGB1induced by T. gondii infection.•Resveratrol reduces HMGB1 mediated TLR4/NF-κB signaling pathway in hepatocytes.