AUTHOR=Zhang Yubing , Li Lili , Qin Song , Yuan Jingyi , Xie Xiaonan , Wang Fan , Hu Shanliang , Yi Yuetao , Chen Min 

TITLE=C-phycocyanin alleviated cisplatin-induced oxidative stress and inflammation via gut microbiota—metabolites axis in mice

JOURNAL=Frontiers in Nutrition

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2022.996614

DOI=10.3389/fnut.2022.996614

ISSN=2296-861X

ABSTRACT=<p>C-phycocyanin is a natural protein extracted from <italic>Spirulina platensis</italic>. We aim to investigate the preventive effect of C-phycocyanin on cisplatin chemotherapy-induced oxidative damage and inflammation. The result showed that C-phycocyanin treatment reduced cisplatin-induced mortality and inflammation including decreased levels of serum IL6, kidney MCP1, and liver IL1β. Furthermore, C-phycocyanin also exerted antioxidant effects on mice, including increased GSH-Px, GGT, and GSH levels in the liver and increased CAT and SOD levels in the kidney. HepG2 cells experiments showed that C-phycocyanin exhibited none of the prevention effects on cisplatin injury. <italic>Faecalibaculum</italic> showed the greatest reduction among genera after cisplatin treatment, which was related to the enrichment of <italic>Romboutsia</italic> and <italic>Lactobacillus</italic> genera. C-phycocyanin treatment reduced the populations of harmful bacteria of <italic>Enterococcus faecalis</italic>, which was positively correlated with inflammation induced by cisplatin. C-phycocyanin increased the contents of 23-nordeoxycholic acid and β-muricholic acid. Moreover, C-phycocyanin increased amino acid-related metabolites, N<sub>α</sub>-acetyl-arginine and trimethyl-lysine contents, and decreased fatty acid esters of hydroxy fatty acids (FAHFAs) contents. In conclusion, C-phycocyanin inhibited inflammation <italic>via</italic> the 23-nordeoxycholic acid-<italic>Enterococcus faecalis</italic>-inflammation axis, and enhanced the antioxidant capacity of kidney <italic>via Lactobacillus</italic>-NRF2 pathway. C-phycocyanin alleviated cisplatin injury <italic>via</italic> the modulation of gut microbiota, especially <italic>Lactobacillus</italic> and <italic>Enterococcus</italic>, as well as regulation of metabolites, especially bile acid and FAHFAs, which highlight the effect of C-phycocyanin and provide a new strategy to prevent cisplatin injury.</p>