Hepatotoxic effect of cadmium chloride and the ameliorating role of Curcumin in rats: histological, biochemical, immunohistochemical study and targeting NF-ĸB/p53/Bcl-2 pathway

Abstract

Cadmium is a dangerous environmental contaminant that injures multiple organs, including the liver. Curcumin is a powerful anti-tumoral, anti-inflammatory, anti-carcinogenic, and hepatoprotective substance. The purpose of this study was to analyze the influence of Cadmium Chloride on rat livers (histopathological, immunohistochemical and molecular changes) and to investigate curcumin’s possible protective role against these changes. The work was performed on 30 adult male Sprague-Dawley albino rats, and it was equally divided into three groups. The duration of the study was 14 days. This study was conducted by administering a dose of cadmium 3 mg/kg/day orally in saline solution. The control group received no medication, group II was administered with CdCl2, and group III was administered with CdCl2 and treated with 2 mg/kg/day Curcumin. Cadmium Chloride disturbed the hepatic architecture, with higher serum levels of liver enzyme alkaline phosphatase (ALP), alanine transaminase (ALT), and aspartate transaminase (AST). Additionally, there was an increased level of fibrosis. The area percentage of the apoptotic protein Bax immunoreactivity (positive Bax immune expression) was raised by Cadmium Chloride, and the transcription of the nuclear factor-kappa B (NF-ĸB) and p53 genes was increased, while the B cell lymphoma-2 (Bcl-2) gene was significantly downregulated. Curcumin improves liver damage, and apoptosis caused by Cadmium Chloride and improves the histopathological changes and anti-apoptotic activity through NF-ĸB/p53/Bcl-2 Pathway which makes Curcumin as a promising adjunctive therapy particularly when there has been lots of industrial and occupational exposure to high levels of cadmium.