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

Abstract

Background: 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. Objective: it was aimed to investigate the impact of thymoquinone (TQ) in mercuric chloride (HgCl 2 )-induced nephrotoxicity through estimation of various proteins involved in natural defense mechanisms. Material and methods: HgCl 2 (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 HgCl 2 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. Results: TQ significantly attenuated hazardous effects of HgCl 2 on renal and hepatic tissues. Urine albumin and glucose were considerably low in the treated groups in comparison with the HgCl 2 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 HgCl 2 -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). Conclusion: TQ showed protective effects against HgCl 2 -induced nephrotoxicity through modifications of various constitutive and inducible protein and enzyme levels in renal tissues.

Mercuric Chloride Induced Nephrotoxicity: Ameliorative Effect of Carica papaya Leaves Confirmed by Histopathology, Immunohistochemistry, and Gene Expression Studies

“…This protection may be attributed to the restoration of antioxidant enzymes such as CAT, GR, GSH, and GST and a decrease in oxidative stress markers (OH) that reduced the accumulation of HgCl 2 in the kidneys and protected them from damage ( Table 4 ). Besides ECP, various medicinal plants such as Adansonia digitata, ( 67 ) curcumin, 68 flaxseeds, 69 Nigella sativa, 70 Polygonum minus, 71 pomegranate seed, 72 Rheum turkestanicum , 45 and Tribulus terrestris ( 73 ) protect the kidneys from HgCl 2 -induced renal damage by increasing antioxidant enzymes and decreasing oxidative stress markers. 73 − 75 However, in this study, 600 mg/kg b.w.…”

Exploring the Potential of Thymoquinone-Stabilized Selenium Nanoparticles: In HEC1B Endometrial Cancer Cells Revealing Enhanced Anticancer Efficacy

“…It is often grown in Asian and Mediterranean countries and is widely used in traditional medicine. − The seeds of this plant and their essential oils are the bioactive component of thymoquinone (TQ) (2-isopropyl-5-methylbenzo-1, 4-quinone, MW = 164.2) . A wide variety of pharmacological activities of TQ such as anti-inflammatory, immunostimulant, antioxidant, antimicrobial, antidiabetic, hepatoprotective, and cardioprotective have been reported. − However, chemotherapeutic and chemopreventive effects of TQ in cancer have also been reported . In different preclinical studies, it has been shown that TQ plays a beneficial role in the control of inflammatory diseases due to its strong antioxidant activity .…”