Oxidative stress and neurobehavioural changes in rats following copper exposure and their response to MiADMSA and d-penicillamine. (24th April 2019)

• Record Type: Journal Article
• Authors: Quamar, Shaheen; Kumar, Jayant; Mishra, Awanish; Flora, SJS
• Is Part Of: Toxicology research and application. Volume 3(2019)
• Publication Date: 2019-04-24
• Subjects: Copper toxicity -- chelation therapy -- D-penicillamine -- MiADMSA -- oxidative stress; Toxicology -- Periodicals; 571.9505
• DOI: 10.1177/2397847319844782
• Languages: English
• ISSNs: 2397-8473

Abstract

An increase in copper concentration in body may lead to hepatolenticular degeneration which is considered as one clinical feature of Wilson's disease. Chelation therapy usingd -penicillamine is the preferred medical treatment for reducing the toxic effects of copper. However, a few shortcomings associated withd -penicillamine led us to search of an alternative antidote for copper toxicity. Monoisoamyl-2, 3-dimercaptosuccinic acid (MiADMSA), a potent arsenic chelator under clinical trial, has been reported to reduce system copper level. Thus, the present study was envisaged to explore the ameliorative effect of MiADMSA against copper toxicity. Copper pre-exposed animals (CuSO4 .5H2 O; 100 mg/kg; p.o., for 6 weeks) were segregated in different groups and were administered equimolar dose (0.3 mEq/kg/day; p.o.) ofd -penicillamine and MiADMSA for 5 days. The effect of different treatments on spontaneous locomotor activity, muscle coordination, depression like behaviour and contextual fear memory was analysed using neurobehavioural battery test. Biochemical variables related to oxidative stress, zinc and copper concentration were determined in liver, kidney and brain. The results suggested that copper exposure led to oxidative stress in liver, kidney and blood, along with moderate effects in brain. Treatment withd -penicillamine and MiADMSA reduced liver copper load. MiADMSA produced more pronounced beneficial effect compared tod -penicillamine by increasing brain GPx activity. Our study suggests that MiADMSA might be equally effective asd -penicillamine in depleting body copper load. More detailed studies using different doses are required to suggest whether MiADMSA could be an alternative ford -penicillamine in reducing oxidative injury, neurobehavioural changes and depleting body copper burden.