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This study aimed to evaluate the protective effect of tannic acid (TA, a natural polyphenol) against MSG-induced hepatotoxicity through the glutathione and thioredoxin systems. Twenty-four rats were randomly divided into control and experimental groups and treated with TA, MSG, and MSG+TA once daily by oral gavage for 21\u00a0days. In addition to major oxidative stress indicators (total glutathione; GSH\u2009+\u2009GSSG and malondialdehyde; MDA), mRNA expression changes and biological activity responses of components of the glutathione and thioredoxin systems were examined in the liver tissues of all animals. The results showed that MSG alone negatively affected both stress indicators and antioxidant system components (glutathione peroxidase; GPx, glutathione reductase; GR, glutathione-S-transferase; GST, and thioredoxin reductase; TrxR) in terms of mRNA expression and biological activity. However, the combination of MSG and TA demonstrated robust antioxidative effects, surpassing the outcomes of MSG treatment. Our results provide new insights into pivotal molecular targets and protective candidates that should be focused on in future in vivo and in vitro HCC research.<\/jats:p>","DOI":"10.1007\/s00210-025-04279-5","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T05:42:30Z","timestamp":1747806150000},"page":"15873-15883","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Investigation of the effects of monosodium glutamate and tannic acid on the glutathione and thioredoxin systems in the liver of rats"],"prefix":"10.1007","volume":"398","author":[{"given":"Mohammad A. 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