The ameliorative potential of Alda-1 on experimentally induced liver fibrosis in adult male mice. A histological, immunohistochemical and biochemical study.

Abstract

Introduction:Because of its complex pathogenesis, liver fibrosis remains one of the diseases with no standard treatment. Alda-1 is considered as a promising drug in ameliorating such fibrosis. Aim of the Work:To evaluate the potential effect of Alda-1 after thioacetamide (TAA)-induced liver fibrosis in male mice. Materials and Methods: Twenty-five adult male mice (25-27 gm aged 2-3 months) were allocated into five equal groups. Group I (control group), group II (Alda-1 group): each mouse was given Alda-1 [5 mg/kg, intraperitoneally (ip)] twice weekly for four weeks. Group III (TAA group): each animal received TAA (200 mg/kg, ip) twice weekly for seven weeks. Group IV (TAA +Alda-1 group): each mouse was given TAA as group III. After stoppage of TAA administration, Alda-1 was given at a dose as group II and continued for four weeks. Group V (recovery group) each animal received TAA treatment as group III and left without any treatment for an extra four weeks. The histological changes were identified by the light (H&E and Masson's trichrome stains) and electron microscopies, immunohistochemical and morphometric analysis. Blood samples were taken to evaluate the liver's function. Results: TAA caused marked histological and biochemical attenuation of hepatocytes structure and function with significant increase in collagen deposition. In addition, TAA caused significant elevation of liver enzymes. In Alda-1treated In Alda-1treated group (IV), hepatocytes revealed nearly normal structure, significantly decreased the elevated liver enzymes and significant increase in reduced glutathione and decrease in malondialdehyde in liver homogenate. Alda-1 decreased the elevated transforming growth factor, collagen-1 gene expression and the area percentage of collagen. In addition, alpha smooth muscle actin was significantly reduced. The anti-inflammatory effects were also detected by the decrease in the interleukin-6 and tumor necrosis factor-α. Conclusion: Alda-1 ameliorated TAA-induced liver fibrosis in mice. This might be due to its antioxidant, antifibrotic and anti-inflammatory effects.

Protective Effects of Crocin Against Methotrexate-Induced Hepatotoxicity in Adult Male Albino Rats: Histological, Immunohistochemical, and Biochemical Study

“…On day 16, a day following MTX injection, by i.p. injection of 50 mg/kg of ketamine and 5 mg/kg of xylazine, rats were anesthetized [ 18 ]. Blood samples were drawn from the abdominal aorta and left to stand for four hours at ambient temperature before being spun in a centrifuge to separate the serum from the blood cells, which were then used for various biochemical assays.…”

Pharmaceutical Strategies to Improve Druggability of Potential Drug Candidates in Nonalcoholic Fatty Liver Disease Therapy

“…Upon activation, the HSCs lose the storage of vitamin A and become proliferative. They also show increased expression of smooth muscle α-actin (SMA) and transforming growth factor-β1 (TGF-β1), which are primarily responsible for the deposition of type I collagen in the extracellular matrix (ECM) [ 17 ]. Hepatocellular ballooning and lobular inflammation with the absence or presence of a certain degree of fibrosis are the primary features of NASH.…”