P2.26 Effect of Thymoquinon on 1,2-Dimethyl-Hydrazine-Induced Oxidative Stress During Initiation and Promotion of Colon Carcinogenesis in Rats

ABSTRACT Objective We evaluated pre- and post-thymoquinon (TQ) treatment on 1,2-dimethyl-hydrazine (DMH)-induced oxidative stress during initiation (10 weeks) and promotion (20 weeks) phases of colon carcinogenesis. Methods Rats were cancer induced with DMH (20 mg/kg) for 10 or 20 weeks, and treated with TQ (5 mg/kg). Following sacrifice, the colons were analyzed for tumor development (incidence, multiplicity and size), lipid peroxidation [conjugated diene (CD), antioxidant enzymatic activities [malondialdehyde (MDA)], glutathione peroxidase (GPx) and catalase (CAT)], and histological changes. Results Increased lipid peroxidation was seen during colon tumor initiation and promotion, and increased GPx and CAT activities during initiation were associated with moderate colon dysplasia, and 30 % tumor incidence. In contrast, while GPx and CAT activities were virtually unchanged at promotion, marked dysplasia and 100 % tumor incidence was observed. Pre-treatment with TQ restored completely DMH-induced oxidative stress at initiation, and inhibited histological changes and tumor development. Pre-treatment with TQ also abrogated the aggravation of oxidative status at promotion, and significantly reduced tumor incidence by 67 %. By comparison, post-treatment withTQ corrected oxidative status at initiation, and attenuated tumour development, but did not correct the nuclear loss of polarity. TQ slightly reduced MDA level and antioxidant enzymatic activities at promotion, with a slight reduction in both tumor state and dysplasia degree. Conclusions TQ is a protective and curative treatment against DMH-induced oxidative stress, during initiation more so than promotion stage of colon cancer in rat. These in vivo results support the notion of possible use of TQ as therapy of human colorectal cancer.