Relationship of antioxidant and oxidative stress markers in different organs following copper toxicity in a rat model

Journal Article · Mon Feb 15 04:00:00 EST 2016 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/J.TAAP.2016.01.007· OSTI ID:22687899

Kumar, Vijay ^[1]; Kalita, Jayantee ^[1]; Bora, Himangsu K. ^[2]; Misra, Usha K. ^[1]

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1. Department of Neurology, Sanjay Gandhi Post Graduate Medical Sciences, Lucknow (India)
2. National Laboratory Animal Centre, CSIR-Central Drug Research Institute, Lucknow (India)

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 (CuSO{sub 4}) induced oxidative stress at different time duration. Fifty-four male Wistar rats (weight range = 205 ± 10 g) were equally divided into three groups. CuSO{sub 4} was administered orally to the experimental groups (Group-II and III) up to 90 days in a dose of 100 and 200 mg/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 CuSO{sub 4} 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 CuSO{sub 4} exposure in a rat model. These levels correlated with the respective organ dysfunction and tissue free Cu concentration. - Highlights: • Oral dosing of CuSO{sub 4} leads to oxidative stress in liver, brain and kidney. • Liver has maximum oxidative stress followed by brain and kidney. • Oxidative stress correlated with the respective organ dysfunction and tissue Cu concentration.

• OSTI ID: 22687899
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Vol. 293; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AMINOTRANSFERASES
ANIMAL TISSUES
ANTIOXIDANTS
BILIRUBIN
BLOOD
BRAIN
COPPER
COPPER SULFATES
CREATININE
GLUTATHIONE
KIDNEYS
LIVER
OXIDATION
RATS
TANTALUM CARBIDES
TOXICITY
UREA