Biochemical modulation of cell energy by 2-deoxyglucose and malonate in 7,12-dimethylbenz(a)anthracene-induced carcinogenesis in rats

• Published in: Toxicology and industrial health Vol. 31; no. 4; pp. 343 - 350
• Main Authors: Moselhy, Said S, Kumosani, TA, Al-Malki, AL, Naif, Almalki A
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.04.2015; Sage Publications Ltd
• Subjects: 9,10-Dimethyl-1,2-benzanthracene - toxicity; Adenosine; Alternative energy; Animals; Apoptosis; Biochemistry; Breast cancer; Cancer therapies; Carcinogens - toxicity; Cytochrome; Deoxyglucose - administration & dosage; Deoxyglucose - metabolism; Drug dosages; Energy Metabolism - drug effects; Enzymes; Female; Free radicals; Glucose; Hydrogen peroxide; Malonates - administration & dosage; Malonates - metabolism; Metabolism; Mitochondria; Nitric oxide; Oxidation; Oxidative stress; Oxidative Stress - drug effects; Phosphorylation; Random Allocation; Rats; Rats, Sprague-Dawley; Sodium; Toxicology; Saudi Arabia; DMBA; rats; Cell energy; oxidative stress
• ISSN: 0748-2337; 1477-0393
• DOI: 10.1177/0748233712472525

The goal of this study was to explore the impact of 2-deoxglucose or malonate individually or in combination on the level of cell energy (adenosine-5′-triphosphate) and oxidative stress in 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary proliferation in rats. A total of 60 adult female Sprague Dawley rats were randomly divided into five groups (12 rats each): group I serves as the control group. Rats in groups (II–V) were administrated intragastrically a single dose of 50 mg/kg body weight (bw) of DMBA. A day after DMBA administration, rats in group III were injected intraperitoneally (ip) with 100 mg 2-deoxyglucose (2-DG)/kg bw daily. Rats in group IV were injected ip with 10 mg sodium malonate/kg bw daily. Rats in group V were injected ip with 100 mg 2-DG/kg bw and 10 mg sodium malonate/kg bw (treatment for 90 days). The results obtained showed that DMBA induced oxidative stress by decreasing the activities of glutathione reductase (GRase) and superoxide dismutase (SOD), glutathione peroxidase (GPx) and elevating the levels of malondialdehyde (MDA) and nitric oxide (NO) in mammary tissues when compared with control. The combined treatment protected against the previous deleterious changes by a significant elevation in the activities of GRase and SOD, GPx and lowering the levels of MDA and NO more potentially when compared with individual treatment. Apoptosis, as indicated by a significant release of cytochrome c from mitochondria into the cytosol, observed in DMBA-injected rats was positively significantly correlated with the elevation of the level of NO. These data explained the possible additive effect of 2-DG and malonate by depleting the cell energy by their protective effects against the earlier stages of carcinogenesis.