Anti-aging effect of DL-β-hydroxybutyrate against hepatic cellular senescence induced by D-galactose or γ-irradiation via autophagic flux stimulation in male rats

• Published in: Archives of gerontology and geriatrics Vol. 92; p. 104288
• Main Authors: Habieb, M.E., Mohamed, M.A., El Gamal, D.M., Hawas, A.M., Mohamed, T.M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-01-2021
• Subjects: 3-Hydroxybutyric Acid; Aging; Animals; Autophagy; Cellular Senescence; D-galacose; Galactose - pharmacology; Humans; Ionizing radiation; Liver; Male; Rats; Senescence; β-hydroxybutyric acid; Ionizing radiation; Senescence; β-hydroxybutyric acid; Autophagy; D-galacose
• ISSN: 0167-4943; 1872-6976
• DOI: 10.1016/j.archger.2020.104288

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•Induction of hepatic senescence (aging) by d-galactose or γ- irradiation.•D-galactose or γ- irradiation increased mRNA levels of p21CIP1 and p16INK4A.•D-galactose reduced Lc3-II/Lc3-I ratio (autophagy parameters).•βOHB acts as cutting–edge solution for hepatic cellular senescence.
The present study aims to shed new light on anti-aging effect of DL-β-hydroxybutyrate (βOHB) against hepatic cellular senescence induced by d-galactose or γ-irradiation. The rats divided into 6 groups. Group 1, control, group 2, exposed to γ-ray (5 GY), group 3, injected by d-galactose (150 mg/kg) daily for consecutive 6 weeks, which regarded to induce the aging, group 4, injected intraperitoneal by β-hydroxybutyrate (βOHB) (72.8 mg/kg) daily for consecutive 14 days, group 5, exposed to γ-ray then treated with βOHB daily for consecutive 14 days, group 6, injected daily with d-galactose for consecutive 6 weeks, then treated with βOHB daily at the last two weeks of d-galactose. Aspartate amino transferase (AST), alanine amino transferase (ALT), Insulin, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were estimated in serum. Moreover, protein expression of Microtubule-associated proteins 1A/1B light chain 3B (LC3-II/LC3-I) ratio, mechanistic target of rapamycin (mTOR), pAMPK, mRNA gene expression of 5′ AMP-activated protein kinase (AMPK), Nucleoporin p62 (p62), cyclin-dependent kinase inhibitor 1(P21CIP1), cyclin-dependent kinase inhibitor 2A (p16INK4a) and DNA fragmentation percentage were measured in liver tissue as a biomarker of cellular senescence. The results confirmed that βOHB modulated serum level of AST, ALT, insulin, IL-6 and TNF-α, protein expression of mTOR and LC3-II/LC3-I ratio, pAMPK and p62 in liver aging model induced by d-galactose or γ-irradiation. Histopathological examination results of liver tissue indicated coincidence with those recorded by molecular biochemical inspection. Taken together, these findings suggest that βOHB may be useful in combating hepatic cellular senescence induced by d-galactose or γ-irradiation via autophagy dependent mechanisms.