Effects of Copper Nicotinate Complex on Renal Metallothionein and Metal-Responsive Transcription Factor 1 Genes Expression During 4-Dimethylaminoazobenzene Exposure in Rats

Neveen A. Hussein, Mona A. Yehia


Background: The expression of MT genes in animal's body is rapidly elevated in response to metal and agents which cause oxidative stress and/or inflammation. The MTF-1 plays an essential role in regulating transcription of MT gene in response to metal ions and oxidative stress. Metalloviatamin complex was found to exhibit anti-tumor and anti-inflammatory activity, cytoprotective effect and reduces oxidative stress.

Objectives: The study was designed to evaluate effects of a daily dose of copper nicotinate complex (CNC) on metallothionein-III (MT-III) and metal-responsive transcription factor -1 (MTF-1) expression during 4-dimethylaminoazobenzene (DAB) exposure.

Methods: Ninety rats were divided into five groups. Group I rats were fed on standard diet and was considered the control group; group II rats were fed on standard diet containing DAB (0.06g/100g diet daily) for six months; group III rats received CNC dissolved in saline solution (1mg/kg body weight daily) for six months; group IV rats were pretreated with CNC one month before DAB; group V rats were post treated with CNC after one month of starting feeding on DAB. MT-III and MTF-1 genes expression was assayed by PCR. Renal histopathological changes were examined by light microscopy.

Results: Genes expression in all groups was statistically high at all time intervals as compared with control group, while it was decreased in groups III, IV and V as compared to cancer group (II). In group IV and V, the genes expression was statistically increased as compared with group III. MT expression in control group declined with age, while it was higher at 6th month than 2nd and 4th month in group II. MTF-1 expression was increased at 4th month followed by decrease at 6th month in all studied groups. These results were confirmed by histopathological change. There was an increase in pyknotic and necrotic nuclei in tubular epithelial cells and a mild dilatation of renal tubules.

Conclusion: Scavenging ROS during DAB-induced oxidative stress may be the major role of MT. CNC causes a partial improvement in the genes expression as well as renal tubules, so CNC may be a promising candidate used for protection against oxidative stress.

 Keywords: Copper nicotinate complex, 4-Dimethylaminoazobenzene, Metallothionein, Metal-responsive transcription factor-1.

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