Sodium Butyrate as Adjuvant Therapy with Mycophenolate Mofetil for Amelioration of Skin Fibrosis in Bleomycin-induced Scleroderma in Mice via Immunomodulatory, Antioxidant, Antiapoptotic and Antifibrotic Mechanisms

Abstract

Background: Scleroderma is an autoimmune, multi-organ disease; its clinical hallmark is cutaneous and systemic fibrosis. Up to date, there is no definite cure. Aim of the Study: The aim of this study was to investigate the potential effects of sodium butyrate (NaB), and mycophenolate mofetil (MMF) each alone or both in a mice model of scleroderma induced by bleomycin (BLM), and to clarify some of their possible mechanisms on oxidative stress, immunological pattern, apoptosis, inflammation and fibrosis. Methods: This study was carried out on 50 Balb/C mice, divided into 5 equal groups. Serum levels of anticentromere antibody (ACA), and skin tissue levels of the following parameters were assayed: transforming growth factor-β1 (TGF-β1), interleukin-4 (IL-4), malondialdehyde (MDA), and superoxide dismutase (SOD). Tissue sections were examined for histopathological changes, dermal thickness, and immunohistochemical expression of caspase- 3, and α-smooth muscle actin (α-SMA). Results and Conclusion: The combined group showed a significant decline in TGF-β1, IL-4, MDA levels, caspase-3, and α-SMA, as well as a significant increase in SOD. Moreover, marked reduction in dermal fibrosis and dermal thickness compared to monotherapy by either NaB or MMF. The combination of NaB and MMF is a promising candidate for the treatment of scleroderma.