Short-term administration of tibolone reduces inflammation and oxidative stress in the hippocampus of ovariectomized rats fed high-fat and high-fructose

• Published in: Nutritional neuroscience 2023-04, Vol.26 (4), p.275-289
• Main Authors: Estrada-Cruz, Norma A., Manuel-Apolinar, Leticia, Segura-Uribe, Julia J., Almanza-Pérez, Julio C., Fortis-Barrera, Ángeles, Orozco-Suárez, Sandra, Bautista-Poblet, Guadalupe, Coyoy-Salgado, Angélica, Guerra-Araiza, Christian
• Format: Article
• Language: English
• Subjects: Animals; Body Weight; Diet, High-Fat - adverse effects; estrogenic decline; Female; Fructose - adverse effects; high-fat-and-high-fructose diet; hippocampus; Hippocampus - metabolism; hormone receptor antagonists; hormone receptors; Hormones - metabolism; Hormones - pharmacology; inflammation; Inflammation - metabolism; Overnutrition; Oxidative Stress; Rats
• ISSN: 1028-415X; 1476-8305
• DOI: 10.1080/1028415X.2022.2046964

Inflammation and oxidative stress are critical events involved in neurodegeneration. In animal models, it has been shown that chronic consumption of a hypercaloric diet, which leads to inflammatory processes, affects the hippocampus, a brain region fundamental for learning and memory processes. In addition, advanced age and menopause are risk factors for neurodegeneration. Hormone replacement therapy (HRT) ameliorates menopause symptoms. Tibolone (TB), a synthetic hormone, exerts estrogenic, progestogenic and androgenic effects on different tissues. We aimed to determine the effect of short-term TB administration on oxidative stress and inflammation markers in the hippocampus of ovariectomized rats fed a high-fat-and-fructose diet (HFFD). Adult female rats were ovariectomized (OVX) and fed standard diet or HFFD-consisting of 10% lard supplemented chow and 20% high-fructose syrup in the drinking water-and administered vehicle or TB (1 mg/kg for seven days). Finally, we administered hormone receptor antagonists (MPP, RU486 or FLU) to each of the OVX + HFFD + TB groups. Bodyweight, triglycerides and cholesterol, oxidative stress and inflammation markers, and the activity and expression of antioxidant enzymes were quantified in the hippocampus of each experimental group. We observed that short-term TB administration significantly reduced body weight, AGEs, MDA levels, increased SOD and GPx activity, improved GSH/GSSG ratio, and reduced IL-6 and TNF-α. Our findings suggest that short-term administration of TB decreases oxidative stress and reduces inflammation caused by HFFD and early estrogenic decline. These effects occurred via estrogen receptor alpha.