Thymoquinone Induces Nrf2 Mediated Adaptive Homeostasis: Implication for Mercuric Chloride-Induced Nephrotoxicity

the primary function of the kidney is to eliminate metabolic waste products and xenobiotics from the circulation. During this process, the kidney may become vulnerable to toxicity.

it was aimed to investigate the impact of thymoquinone (TQ) in mercuric chloride (HgCl₂)-induced nephrotoxicity through estimation of various proteins involved in natural defense mechanisms.

HgCl₂ (0.4 mg/kg) was administered to all groups (n = 5) except for the normal control. Three treatment groups received TQ (5, 10, and 15 mg/kg) 60 min before HgCl₂ administration. The protective effect of TQ was evaluated from renal and liver function biomarkers, urine examination, glomerulus filtration rate (GFR), histopathological features, oxidative stress biomarkers, Hsp-70, apoptosis biomarkers, and gene expression.

TQ significantly attenuated hazardous effects of HgCl₂ on renal and hepatic tissues. Urine albumin and glucose were considerably low in the treated groups in comparison with the HgCl₂ group. TQ treatment also enhanced % GFR in rats. TQ-enhanced superoxide dismutase, catalase, and glutathione levels by enhancing the expression level of nuclear factor erythroid 2-related factor 2 (Nrf2). TQ increased Hsp-70 and Bcl-2 levels and reduced caspase-3 activity. TQ also protected cells against HgCl₂-induced cell death and decreased % DNA fragmentation. TQ increased the expression of protective proteins metallothionein I and II and reduced the expression of kidney injury molecule-1 (Kim-1).

TQ showed protective effects against HgCl₂-induced nephrotoxicity through modifications of various constitutive and inducible protein and enzyme levels in renal tissues.