Combined Effect of N-Acetyl Cysteine, Zinc, and Selenium Against Chronic Dimethylmercury-Induced Oxidative Stress: A Biochemical and Histopathological Approach

Abstract

Mercury (Hg), widely used in industry, is a great environmental health problem for humans and animals. Despite several reports regarding Hg toxicity, there is scarcity of data on its toxic manifestations on Sprague Dawley rats under realistic exposure conditions. Experimental studies have shown that sulphur-containing antioxidants have beneficial effects against the detrimental properties of Hg. The present work was aimed to study the therapeutic potential of combined administration of N-acetyl cysteine (NAC; 2 mmol/kg ip), zinc (Zn; 2 mmol/kg po), and selenium (Se; 0.5 mg/kg po) against dimethylmercury (DMM; 1 mg/kg po)-intoxicated male rats for 12 weeks. Exposure to DMM caused significant alterations in cytochrome P450 (CYP) activity, microsomal lipid peroxidation, and proteins. Activities of transaminases (aspartate aminotransferase/alanine aminotransferase), alkaline phosphatase, and lactate dehydrogenase in serum, as well as activities of CYP enzymes aniline hydroxylase (AH), amidopyrine-N-demethylase (AND) in liver microsomes and activities of acid phosphatase, alkaline phosphatase, glucose-6-phophatase, and succinic dehydrogenase in the liver and kidney, were significantly altered after DMM administration. DMM exposure also induced severe hepato-renal alterations at the histopathological level. NAC, along with Zn and Se, dramatically reversed the alterations in all of the variables more toward control. The study results conclude that protective intervention of combined treatment of NAC, along with Zn and Se, is beneficial in attenuating DMM-induced systemic toxicity.

Ellagic acid: Pharmacological activities and molecular mechanisms involved in liver protection

“…Exposure to mercurial compounds induces hepatotoxicity associated with oxidative stress [182][183][184][185], generating hepatocellular defects like hepatomegaly, centrilobular hepatic steatosis [186,187], decrease in the synthesis of hepatic coagulation factors [188][189][190][191][192] and diminution in the activity of metabolic enzymes [193]. EA reduces mercuric chloride damage, avoiding the generation of oxidative stress and diminishing the possibility of damage to liver cells [194,195].…”

Chelation: Harnessing and Enhancing Heavy Metal Detoxification—A Review

“…Overall, a number of studies have investigated the effects of micronutrients such as vitamins, sulphur-containing amino acids, antioxidants, and essential minerals on kinetics and adverse effects of toxic elements [64–68]. Nutritional status affects uptake, as toxic cations are transported by proteins for essential nutrients such as magnesium, zinc, and iron, putting those who are malnourished at greater risks for toxicity [2, 33].…”

Nephroprotective potential of selenium and taurine against mercuric chloride induced nephropathy in rats

“…These observations have been sustained by reports of other investigators with various metals as aluminum and beryllium administration. 92,93 Joshi et al 94 supported these findings and they stated that the heavy metals induce toxicity through oxidative stress, and the toxicological profile of mercury is associated with a variety of biochemical abnormalities as loss of functional integrity of cell membrane. Takeda et al 95 tried to explain the cause of podocytic processes abnormalities by the podocalyxin/Na + , H + exchange regulatory factor2/ezrin/actin interactions which are disrupted in pathologic conditions associated with changes in glomerular epithelial cell foot processes, indicating their importance for maintaining the unique organization of this epithelium.…”