The present study was designed to investigate the ameliorative effect of curcumin administration on oxidative stress, antioxidant status, DNA fragmentation and caspase-9 gene expression in colon cancer induced by 1, 2-dimethylhydrazine (DMH) in rats. Seventy male albino rats divided into five groups containing 14 rats each. Group Ι:( Control group) rats received no drugs. Group II: (colon cancer induced group) rats injected DMH (35 mg/kg b.wt /week, subcutaneously) for ten weeks. Group III: (DMH+curcumin therapeutic group) rats injected DMH and administered curcumin (100 mg/kg b.wt/day, orally) from the 11th week until the 16th weeks. Group IV: ( DMH+curcumin treated group) rats injected DMH and at the same time administered curcumin for 16 weeks ( end of experiment). Group V: (control +curcumin group) rats administered curcumin all over the experimental periods. At the end of 16th week treatment blood samples and colon tissues were collected for determination of serum lactate dehydrogenase (LDH) and carcino embryonic antigen (CEA) in addition to glutathione peroxidase (GPx), catalase (CAT),superoxide dismutase (SOD), reduced glutathione (GSH), L-malondialdehyde (L-MDA), nitric oxide (NO), glutathione-S-transferase(GST), Caspase-9 gene and DNA fragmentation in colon tissues. The obtained results revealed that, DMH potentially increased serum LDH activity and CEA level. In addition, CAT, GPx, GST activities, MDA, and NO concentrations in colon tissues of DMH injected rats were significantly increased. However, SOD, GSH, Caspase-9 and DNA fragmentation in colon tissues were significantly decreased. Curcumin treatment to colon cancer rats significantly decreased serum LDH and CEA, CAT and GPx activities and attenuated the increased MDA and NO concentrations in colon tissues. On the other hand, curcumin treatment enhanced the activity of SOD and GST and the level of GSH, caspase-9 and DNA fragmentation in colon tissues. From the obtained results it could be concluded that, inhibition of peroxidation and oxidative stress markers and enhanced antioxidant status and increased caspase-9 gene expression and DNA fragmentation in rat colon tissues by curcumin suggest the potential efficacy of curcumin as an addition chemopreventive agent in treatment of colon carcinogenesis.
KEY WORDS: Colon cancer, DMH, Curcumin, DNA fragmentation, caspase-9 gene expression, antioxidant enzymes.
|
