The Impact of Carvedilol on Organ Index, Inflammatory Mediators, Oxidative Stress Parameters and Skin Markers in D-Galactose-Induced Aging Mice

Abstract

Background: Aging processes are defined as those that increase the susceptibility of individuals, as they grow older, to the factors that eventually lead to death. It is a complex multi-factorial process where several factors may interact simultaneously and may operate at many levels of functional organization.. Accumulating evidence has suggested that active ingredients that possess antioxidative and anti-inflammatory proprties could decrease the incidence and development of aging-related diseases and promote longevity. Carvedilol is a non-selective third generation β-blocker/α1-blocker with antioxidant and inflammatory activity to evaluate its antiaging effect and to investigate if it is better to given carvedilol with aging induction or after aging induction is established. Aim: To evaluate the effect of carvedilol on organ index, inflammatory mediators, oxidative stress parameters and skin markers in d-galactose-induced aging mice. Method: Male (swiss albino mice) weighing 20 to 30 g and aged 3 to 6 months was randomly divided into six groups , each consisting of 10 animals (60 mice in total). Group I was given normal saline orally only for six weeks, group II was given d-galactose 500 mg/kg orally only for six weeks, group III was given d-galactose 500 mg/kg orally and vitamin C 100 mg/kg orally concomitantly for six weeks, group IV given d-galactose 500 mg/kg orally only for six weeks, then directly next day after ending of aging induction, vitamin c 100 mg/kg started for another six weeks, group V given d-galactose 500 mg/kg orally and carvedilol 10 mg/kg orally concomitantly for six weeks, group VI given d-galactose 500 mg/kg orally only for six weeks, then directly next day after ending of aging induction, carvedilol 10 mg/kg started for another six weeks. After that, animals were weighed, euthanized, and dissected, the heart was removed and the organ index was calculated. Also the heart tissue is divided in to two parts, one homogenated to measure interleukin-Iβ, tumor necrosis factor-alpha, glutathione peroxidase and malondialdehyde, while the other piece for histopathological analysis to determine the presence of hypertrophy. Skin tissue was taken and homogenated for ELISA assay (measurement of collagen I and III levels ). Results: Results showed a significant decrease in heart organ index in animals that received carvedilol orally administered compared to aged group, with a substantial decrease in inflammatory mediators, malondialdehyde level and a marked increase in glutathione peroxidase level, collagen I and collagen III levels. Furthermore, carvedilol reverses the myocardial hypertrophy induced by D-galactose. Conclusion: The present study suggests that carvedilol has a positive antiaging benefit in reducing oxidative stress, decreasing inflammatory and skin aging markers and improving hypertrophic cardiac cells. Regarding the timing of drug administration, although carvedilol shows a benficial continuing impact when given with and after the initiation of aging. It’s better to give at starting of the aging process to control the aging series as soon as possible