Evaluation of Anti-aging Effects of Gemfibrozil on D-galactose induced Aging Mouse Model

Abstract

Background: Aging is the sequential or progressive changes in the organisms that is associated with increasing susceptibility to disease and death. Advanced age is associated with increased incidence of a variety of chronic disease states that share oxidative stress and inflammation as causative role players. Accumulating evidence in published literature showed that the use of antioxidant and anti-inflammatory agents is an effective approach to alleviate or reverse aging-related changes with consequent reduction of the aging rate and related disease. Gemfibrozil, as a peroxisome proliferator-activated alpha receptor ligand (PPARα), is reported to have antioxidant and inflammatory activity. Aim of the study: Evaluate the anti-aging effect of gemfibrozil on many parameters associated with the aging process on the D-galactose induced aging mice model. Method: The current work was an experimental randomized controlled study in which 60 albino male mice weighing between 25 to 40 gm were randomly divided into 6 groups (10 mice each group). group1 apparently healthy group, receive normal saline orally. Group 2 (age induction group receive D-galactose 500 mg/kg) orally only for 6 weeks, group 3 (+D-galactose 500 mg/kg + vitc 100 mg/kg orally for 6 weeks) group 4 (D-galactose 500 mg/kg for 6 weeks then vitc 100 mg/kg for another 6 consecutive weeks group 5 (D-galactose 500 mg/kg + gemfibrozil 7.5 mg/kg concomitantly for 6 weeks) group 6 (D-galactose 500 mg/kg for 6 weeks then gemfibrozil 7.5 mg/kg for another 6 consecutive weeks. Then animals were sacrificed, liver and kidney were weighed for organ index measurement and tissue sections and heart homogenate were prepared for ELISA assay (measurement of TN alpha, IL1beta, SOD, GPX) and histopathological analysis of myocardial tissue. Results: results showed a significant rise in liver and kidney indices in animals that received gemfibrozil orally administered (during and after induction) compared to aged group, with a dramatic decrease in inflammatory and oxidative stress mediator level and a marked reversal effect on myocardial hypertrophy induced by D-galactose. Conclusion: Gemfibrozil oral administration alleviates aging-associated atrophic changes in liver and kidney, oxidative stress and inflammatory state in myocardial tissue and reverses aging-related myocardial hypertrophic changes.