Liver Metabolite Profiles and Oxidative Stress in Ageing Rats and Their Modulation by Tocotrienol-Rich Fraction

Résumé fourni par la source

Ageing alters liver metabolism and function, accompanied by morphological changes in hepatic cells, including disrupted metabolite profiles and structural degeneration. These changes contribute to increased oxidative stress and inflammation. However, the connection between oxidative stress, inflammation, histological changes, and liver metabolism during ageing, and the potential of the tocotrienol-rich fraction (TRF) as a therapeutic agent, remains underexplored. This study investigates age-related hepatic changes and the effects of TRF using metabolomics. Sprague-Dawley rats aged 3, 9, and 21 months were assigned to control and treatment groups and received either palm olein or TRF supplementation. Liver tissues were analysed using untargeted metabolomics via LC-MS/MS, along with histological evaluation and biochemical assessments of antioxidant enzymes (SOD, CAT), inflammatory markers (IL-6, TNF-alpha), and lipid peroxidation markers (MDA). SOD activity declined significantly with age in both control and TRF-treated old rats (p<0.05), suggesting reduced antioxidant defence with increasing age, whereas no significant changes were observed in CAT, IL-6 or MDA levels. Histologically, TRF-treated livers displayed fewer fibroblasts and less inflammation than control livers. Metabolomics showed age-related alterations in taurine and hypotaurine metabolism, pyrimidine metabolism (uridine and uracil), and TCA cycle components (malate and glutamate). These findings demonstrate that TRF modulates age-related liver changes, particularly in morphology and metabolism, despite a persistent decline in antioxidant activity. This finding underscores the potential of TRF in mitigating liver ageing. It provides insight into key metabolic pathways involved, offering a foundation for future therapeutic strategies targeting liver health in the elderly.

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