Ahmed M. Kabel

Conference 2023 Live Talk

Talk title

Sodium valproate reprofiling for amelioration of bleomycin-induced skin fibrosis

Authors and Affiliations

Ahmed M. Kabel1,2, Maaly A. Abd Elmaaboud2

1. National Drug Committee, Academy of Scientific Research and Technology, Cairo, Egypt
2. Department of pharmacology, Faculty of Medicine, Tanta University, Tanta, Egypt

Abstract

Background

Skin fibrosis is one of the connective tissue disorders characterized by skin and systemic fibrosis. Its pathogenesis involves multiple interrelated processes of autoimmunity, vasculopathy, inflammation and oxidative stress. This study was a trial to explore the possible ameliorative effects of sodium valproate on experimental model of skin fibrosis induced by bleomycin.

Methods

Forty male BALB/c mice were divided into four equal groups as follows: control group; bleomycin group; bleomycin + sodium valproate group and sodium valproate group. Mice were assessed for their body weight every four days throughout the whole study. Skin tissues were used to evaluate the oxidative stress parameters, transforming growth factor beta 1 (TGF-β1), tumor necrosis factor alpha (TNF-α), interleukin 15 and mammalian target of rapamycin (mTOR). Skin fibrosis was evaluated by measuring dermal thickness and staining the skin tissues with Masson trichrome stain. Also, the skin tissues were immunostained for detection of alpha smooth muscle actin (α-SMA).

Results

Administration of sodium valproate to bleomycin-treated mice resulted in restoration of the body weight with significant decrease in the dermal thickness, amelioration of oxidative stress, suppression of TGF-β1 and mTOR expression and significant reduction of the percentage of α-SMA immunostaining and the proinflammatory cytokine levels compared to mice treated with bleomycin alone.

Conclusions

Sodium valproate has an antifibrotic effect on skin fibrosis which may represent a beneficial therapeutic modality for management of scleroderma.