L-Glutamine Substantially Improves 5-Fluorouracil-Induced Intestinal Mucositis by Modulating Gut Microbiota and Maintaining the Integrity of the Gut Barrier in Mice.

SCOPE: This study investigates the potential of glutamine to mitigate intestinal mucositis and dysbiosis caused by the chemotherapeutic agent 5-fluorouracil (5-FU). METHODS AND RESULTS: Over twelve days, Institute of Cancer Research (ICR) mice are given low (0.5 mg kg-1) or high (2 mg kg-1) doses of L-Glutamine daily, with 5-FU (50 mg kg-1) administered between days six and nine. Mice receiving only 5-FU exhibited weight loss, diarrhea, abnormal cell growth, and colonic inflammation, correlated with decreased mucin proteins, increased endotoxins, reduced fecal short-chain fatty acids, and altered gut microbiota. Glutamine supplementation counteracted these effects by inhibiting the Toll-like receptor 4/nuclear factor kappa B (TLR4/NF-κB) pathway, modulating nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) oxidative stress proteins, and increasing mammalian target of rapamycin (mTOR) levels, thereby enhancing microbial diversity and protecting intestinal mucosa. CONCLUSIONS: These findings underscore glutamine's potential in preventing 5-FU-induced mucositis by modulating gut microbiota and inflammation pathways.

Trans-2-nonadecyl-4-(hydroxymethyl)-1,3-dioxolane (TNHD) purified from freshwater clams markedly alleviates dimethylnitrosamine-induced hepatic fibrosis.

Liver fibrosis occurs due to injury or inflammation, which results in the excessive production of collagen and the formation of fibrotic scar tissue that impairs liver function. Despite the limited treatment options available, freshwater clams may hold promise in the treatment of liver fibrosis. In this study, we demonstrated the effects of ethanol extract of freshwater clam (FCE), ethyl acetate extract of FCE (EA-FCE), and trans-2-nonadecyl-4-(hydroxymethyl)-1,3-dioxolane (TNHD) on liver fibrosis induced by dimethylnitrosamine (DMN). Administration of FCE and TNHD alleviated liver injury, including tissue damage, necrosis, inflammation scores, fibrosis scores, serum enzymes, and triglyceride levels. Furthermore, we analyzed the expression of fibrosis-related proteins, such as α-smooth muscle actin (α-SMA) and transforming growth factor (TGF-ß), as well as the hydroxyproline content, which decreased after treatment with FCE and TNHD. Animal experiments revealed that FCE and TNHD can reduce liver fibrosis by inhibiting cytokines that activate stellate cells and decreasing extracellular matrix (ECM) secretion. Cell experiments have shown that TNHD inhibits the MAPK/Smad signaling pathway and TGF-ß1 activation, resulting in a reduction in the expression of fibrosis-related proteins. Therefore, freshwater clam extracts, particularly TNHD, may have potential therapeutic and preventive effects for the amelioration of liver fibrosis.