Role of thymoquinone and ebselen in the prevention of sodium arsenite–induced nephrotoxicity in female rats

Abstract

<jats:p> The aim of this study is to investigate the protective effects of thymoquinone (TQ) and ebselen (Eb) on arsenic (As)-induced renal toxicity in female rats. Sodium arsenite was orally administrated at a dose of 20 mg/kg body weight daily for 28 days, either alone or 1 h before TQ (10 mg/kg) or Eb (5 mg/kg) administration. Renal tissue As concentration and oxidative stress markers, including lipid peroxidation (LPO), nitrite/nitrate, and glutathione (GSH) levels, were determined. In addition to the oxidative stress response, antioxidant enzyme activities including that of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were measured. Exposure to As elicited a significant increase in As concentration and significant modifications to the redox state of the kidney, as was evidenced by a significant elevation in LPO and nitrite/nitrate concentration, with a concomitant reduction in GSH content and antioxidant enzyme activity. The oxidant/antioxidant imbalance observed in As toxicity was associated with a significant elevation in renal tumor necrosis factor α, interleukin 6, B-cell lymphoma 2 (Bcl-2)-associated X protein, and caspase 3 levels, in addition to a significant decrease in Bcl-2 levels. Post-administration of TQ and Eb markedly prevented As-induced oxidative stress, inflammation, apoptosis, and As accumulation in the renal tissue and reduced histological renal damage. These findings demonstrate that TQ, the main bioactive phytochemical constituent of Nigella sativa seed oil, and Eb, an organoselenium compound, could significantly inhibit As-induced oxidative damage, apoptosis, and inflammation, and significantly attenuate the accumulation of As in renal tissues by facilitating As biomethylation and excretion. </jats:p>

Nephroprotective Role ofBeta vulgarisL. Root Extract against Chlorpyrifos-Induced Renal Injury in Rats

“…MDA is formed by ROS-induced lipid peroxidation and is commonly used as a biomarker of oxidative stress. Increased MDA levels indicated damage to kidney tissue and altered membrane function [22, 26]. NO is a biological mediator involved in several physiological functions.…”

Nephroprotective effects of chlorogenic acid against sodium arsenite‐induced oxidative stress, inflammation, and apoptosis

“…Inorganic As, in both the arsenite and arsenate forms, is more toxic than methylated As. 2 However, both the organic and inorganic forms are present at high concentrations in soil and water, thereby inducing acute and chronic toxicity in populations worldwide and posing a public health concern. 3 Global estimates suggest that 200 million individuals are affected by As intoxication through contaminated food and water, and occupational exposure.…”

“…8 Arsenic induces oxidative pressure through excessive overproduction of reactive oxygen and nitrogen species (ROS/RNS), depletion of the antioxidant capacity of cells, 5 and suppression of DNA repair mechanisms. 2 Arsenic also depletes the cellular concentrations of both enzymatic and nonenzymatic molecules. 5 This mechanism of As toxicity strongly suggests that antioxidants alleviate As-mediated toxicity.…”

“…Workers in the industries mentioned above face potential exposure to the poisonous effects of As. Inorganic As, in both the arsenite and arsenate forms, is more toxic than methylated As 2 . However, both the organic and inorganic forms are present at high concentrations in soil and water, thereby inducing acute and chronic toxicity in populations worldwide and posing a public health concern 3 .…”

“…To date, several endogenous free radical scavengers (including enzymatic factors such as catalase, superoxide dismutase (SOD), and selenium and / or non‐selenium‐dependent glutathione peroxidase (GPx) and nonenzymatic scavengers, such as glutathione (GSH); bilirubin; albumin; vitamins A, E, and C; selenium, uric acid, and coenzyme Q‐10, have been identified in both the membranes and cytoplasm of cells 8 . Arsenic induces oxidative pressure through excessive overproduction of reactive oxygen and nitrogen species (ROS/RNS), depletion of the antioxidant capacity of cells, 5 and suppression of DNA repair mechanisms 2 . Arsenic also depletes the cellular concentrations of both enzymatic and nonenzymatic molecules 5 .…”