title: A study of dose response and organ susceptibility of copper toxicity in a rat model.
abstract: Copper (Cu) in higher concentration is toxic and results in various organ dysfunction. We report Cu concentration in liver, brain and kidney in the rat model following chronic exposure of oral copper sulphate at different subtoxic doses and correlate the tissue Cu concentrations with respective organ dysfunction. Fifty-four male wistar rats divided in 3 groups, the control group received saline water and the experimental group (Group-IIA and IIB) received oral copper sulphate in dose of 100 and 200mg/kg Body Weight. At the end of 30 days, 60 days and 90 days of exposure, six rats were sacrificed from each group. The maximum peak force in grip strength, latency to fall in rotarod and percentage attention score in Y-maze were significantly reduced in the copper sulphate exposed rats compared to the controls at all time points and these were more marked in Group-IIB compared to Group-IIA. Cu concentration was significantly higher in liver, kidney and brain in the Group-II compared to the Group-I. The Cu concentration was highest in the liver (29 folds) followed by kidney (3 folds) and brain (1.5 folds). Serum ALT, AST and bilirubin correlated with liver Cu, BUN with kidney Cu, and grip strength, rotarod and Y-maze findings correlated with brain Cu level. In rats, chronic oral copper sulphate exposure at subtoxic level results in neurobehavioral abnormality and liver and kidney dysfunctions due to increased Cu concentration in the respective organs. Liver is the most vulnerable organ and copper toxicity increases with increasing dose and duration of exposure.
authors.affiliation: Department of Neurology, Sanjay Gandhi Post Graduate Medical Sciences, Raebareily Road, Lucknow 226014, India.
authors.forename: Vijay
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Department of Neurology, Sanjay Gandhi Post Graduate Medical Sciences, Raebareily Road, Lucknow 226014, India. Electronic address: jayanteek@yahoo.com.
authors.forename: Jayantee
authors.initials: J
authors.lastname: Kalita
authors.affiliation: Department of Neurology, Sanjay Gandhi Post Graduate Medical Sciences, Raebareily Road, Lucknow 226014, India.
authors.forename: U K
authors.initials: UK
authors.lastname: Misra
authors.affiliation: Laboratory Animal Division, Central Drug Research Institute, Lucknow, India.
authors.forename: H K
authors.initials: HK
authors.lastname: Bora
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D003300:Copper / Q000633:toxicity*; D018737:Hand Strength; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D023421:Models, Animal; D009043:Motor Activity / Q000187:drug effects; D009928:Organ Specificity / Q000187:drug effects*; D017208:Rats, Wistar; D012044:Regression Analysis
chemical_list: D003300:Copper
keywords: Brain; Copper; Kidney; Liver; Toxicity