Mitigation of Cu(II)-induced damage in human blood cells by carnosine: An in vitro study. (October 2020)

• Record Type: Journal Article
• Authors: Husain, Nazim; Mahmood, Riaz
• Is Part Of: Toxicology in vitro. Volume 68(2020)
• Publication Date: 2020-10
• Subjects: Copper -- Carnosine -- Oxidative stress -- Blood -- Antioxidant -- DNA damage; ABTS 2, 2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) -- AMP adenosine 5′-monophosphate. -- AO antioxidant -- AFR ascorbate free radical -- ATP adenosine 5′-triphosphate -- Cu copper -- CuCl2 copper chloride -- CUPRAC cupric reducing antioxidant capacity -- SOD Cu, Zn superoxide dismutase -- DPPH 2, 2-diphenyl-1-picrylhydrazyl -- DHE dihydroethidium -- DCFH-DA 2, 7-dichlorodihydrofluorescein diacetate -- DTNB 5, 5′-dithiobisnitrobenzoic acid -- FRAP ferric reducing AO power -- G6PD glucose 6-phosphate dehydrogenase -- LPO lipid peroxidation -- MetHb methemoglobin -- NAD+ oxidized nicotinamide adenine dinucleotide -- NADH reduced nicotinamide adenine dinucleotide -- NADP+ oxidized nicotinamide adenine dinucleotide phosphate -- NADPH reduced nicotinamide adenine dinucleotide phosphate -- NO nitric oxide -- PMRS plasma membrane redox system -- ROS reactive oxygen species -- RNS reactive nitrogen species -- GSH reduced glutathione -- GSSG oxidized glutathione -- TBS Tris-buffered saline -- Tris tris(hydroxymethyl)aminomethane -- H2O2 hydrogen peroxide; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2020.104956
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: Copper (Cu) is an essential micronutrient but human exposure to high level of this metal results in adverse health effects. Oxidative stress is assumed to play a major role in the mechanism of Cu-induced toxicity. The protective role of carnosine, an antioxidant and antiglycating agent, was examined against Cu-induced toxicity in isolated human blood cells. Red blood cells (RBC) were treated with 0.5 mM copper chloride (CuCl2 ), a Cu(II) compound, either alone or after treatment with carnosine. Incubation of RBC with CuCl2 increased protein oxidation, lipid peroxidation, methemoglobin formation and lowered glutathione content. The antioxidant defense system was impaired and production of reactive oxygen (ROS) and reactive nitrogen species (RNS) was enhanced. Pre-incubation of RBC with carnosine protected the cells against CuCl2 -induced oxidative damage. It restored the activities of several antioxidant, membrane-bound and metabolic enzymes, decreased the generation of ROS and RNS, enhanced the antioxidant power of cells and prevented inactivation of plasma membrane redox system. Carnosine also protected human lymphocytes from CuCl2 -induced DNA damage. The protective effects of carnosine were concentration-dependent while carnosine itself did not exhibit any adverse effect. Carnosine can, therefore, be used as a possible chemoprotectant against the harmful effects of this extremely redox active metal. Highlights: Cu(II) induces oxidative and nitrosative stress in human blood cells. Carnosine pre-treatment lowers ROS and RNS generation. Carnosine protects blood cells from Cu(II)-induced cytotoxicity and genotoxicity.