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
Qamar Othman
Pharmacology Department, Faculty of Medicine, Tanta University, Egypt.
Maaly A. Abdelmaaboud
Pharmacology Department, Faculty of Medicine, Tanta University, Egypt.
Amany A. Abdin
Pharmacology Department, Faculty of Medicine, Tanta University, Egypt.
Fleur Fathi
Pharmacology Department, Faculty of Medicine, Tanta University, Egypt.
*Author to whom correspondence should be addressed.
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.
Keywords: Scleroderma, bleomycin, sodium butyrate, mycophenolate mofetil, oxidative stress, immunological pattern, apoptosis, fibrosis