title: Relationship of antioxidant and oxidative stress markers in different organs following copper toxicity in a rat model.
abstract: Copper (Cu) at a higher level becomes toxic and it can catalyze the formation of highly reactive hydroxyl radical. We report the vulnerability of liver, kidney and brain to different dose of copper sulfate (CuSO4) induced oxidative stress at different time duration. Fifty-four male Wistar rats (weight range=205±10g) were equally divided into three groups. CuSO4 was administered orally to the experimental groups (Group-II and III) up to 90 days in a dose of 100 and 200mg/Kg body weight per day. Saline water was given to the control group (Group-I). At the end of 30, 60 and 90 days of administration, neurobehavioral studies were done and six rats from each group were sacrificed. Their liver, kidney and brain tissues were subjected for Cu, glutathione (GSH), malondialdehyde (MDA) and total antioxidant capacity (TAC) assay. Blood urea nitrogen (BUN), serum creatinine, bilirubin and transaminases were measured. GSH, TAC and MDA levels were correlated with the markers of respective organ dysfunction. Administration of CuSO4 resulted in increased free Cu and MDA level, and decrease GSH and TAC levels in group-II and III compared with group-I. In experimental groups, the reduction in TAC and GSH levels was maximum in liver tissue followed by brain and kidney; whereas increase in MDA level was highest in liver followed by brain and kidney at 30, 60 and 90 days. TAC and GSH levels in the liver inversely correlated with serum transaminases and bilirubin, and tissue free Cu, and positively correlated with MDA levels. Free Cu level in kidney tissue and BUN inversely correlated with TAC and GSH, and positively with MDA level. Grip-strength, rotarod and Y-maze findings were inversely correlated with brain free Cu and MDA levels and positively with GSH and TAC levels. The oxidative stress was highest in liver followed by brain and kidney after oral CuSO4 exposure in a rat model. These levels correlated with the respective organ dysfunction and tissue free Cu concentration.
authors.affiliation: Department of Neurology, Sanjay Gandhi Post Graduate Medical Sciences, Lucknow, India.
authors.forename: Vijay
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Department of Neurology, Sanjay Gandhi Post Graduate Medical Sciences, Lucknow, India. Electronic address: jayanteek@yahoo.com.
authors.forename: Jayantee
authors.initials: J
authors.lastname: Kalita
authors.affiliation: National Laboratory Animal Centre, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Himangsu K
authors.initials: HK
authors.lastname: Bora
authors.affiliation: Department of Neurology, Sanjay Gandhi Post Graduate Medical Sciences, Lucknow, India.
authors.forename: Usha K
authors.initials: UK
authors.lastname: Misra
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001806:Blood Urea Nitrogen; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003300:Copper / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D005106:Exploratory Behavior / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D018737:Hand Strength; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D017208:Rats, Wistar; D045442:Rotarod Performance Test
chemical_list: D008315:Malondialdehyde; D003300:Copper; D003404:Creatinine; D005978:Glutathione
keywords: Copper toxicity; Glutathione; Lipid peroxidation; Oxidative stress; Rat; Total antioxidant capacity; Wilson disease