Protective efficacy of thymoquinone or ebselen separately against arsenic-induced hepatotoxicity in rat

Arsenic (As) exposure is associated with adverse health outcomes to the living organisms. In the present study, the hepato-protective ability of thymoquinone (TQ), the active principle of Nigella sativa seed, or ebselen (Eb), an organoselenium compound, against As intoxication in female rats was investigated. For this purpose, animals were allocated randomly into control, As (20 mg/kg), TQ (10 mg/kg), Eb (5 mg/kg), As+TQ, and As+Eb groups that were orally administered for 28 consecutive days. Arsenic exposure resulted in hepatic oxidative damage which was evidenced by marked decreases in antioxidant parameters (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione (GSH)) concomitant with high malondialdehyde (MDA) level. Furthermore, As toxicity induced significant elevations in liver accumulation of As, serum hepatic indices (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin (TB)), and apoptotic marker (B cell lymphoma 2(Bcl2), Bcl-2-associated X protein (Bax), and caspase 3) levels. Additionally, notable increments in hepatic fibrotic markers (epidermal growth factor (EFG) and transforming growth factor beta 1 (TGF-β1)) associated with high nitric oxide, interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and myeloperoxidase (MPO) levels were noticed following As intoxication. Biochemical findings were well-supported by hepatic histopathological screening. The co-treatment of As-exposed rats with TQ or Eb considerably improved liver function and antioxidant status together with lessened hepatic As content, inflammation, apoptosis, and fibrosis. The overall outcomes demonstrated that TQ or Eb ameliorates As-induced liver injury through their favorable antioxidant, anti-inflammatory, anti-apoptotic, and fibrolytic properties.

Keywords: Apoptosis; Arsenic exposure; Ebselen; Fibrosis; Inflammation; Liver; Oxidative stress; Thymoquinone.