Liver Cancer
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Oct 28, 2008; 14(40): 6145-6153
Published online Oct 28, 2008. doi: 10.3748/wjg.14.6145
Diallyl sulfide protects against N-nitrosodiethylamine-induced liver tumorigenesis: Role of aldose reductase
Safinaz S Ibrahim, Noha N Nassar
Safinaz S Ibrahim, Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
Noha N Nassar, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
Author contributions: Both authors contributed equally to carrying out the design, execution of the experiments as well as writing up and revision of the manuscript.
Correspondence to: Noha N Nassar, PhD, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El-Aini, Cairo 11562, Egypt. nnagah@gmail.com
Telephone: +20-22-3639307 Fax: +20-22-25320005
Received: June 21, 2008
Revised: September 20, 2008
Accepted: September 27, 2008
Published online: October 28, 2008
Abstract

AIM: To evaluate the protective effect of diallyl sulfide (DAS) against N-nitrosodiethylamine (NDEA)-induced liver carcinogenesis.

METHODS: Male Wistar rats received either NDEA or NDEA together with DAS as protection. Liver energy metabolism was assessed in terms of lactate, pyruvate, lactate/pyruvate, ATP levels, lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G6PD) activities. In addition, membrane disintegration of the liver cells was evaluated by measuring lipid-peroxidation products, measured as malondialdehyde (MDA); nitric oxide (NO) levels; glucose-6-phosphatase (G6Pase), catalase (CAT) and superoxide dismutase (SOD) activities. Liver DNA level, glutathione-S-transferase (GST) and cytochrome c oxidase activities were used as DNA fragmentation indices. Aldose reductase (AR) activity was measured as an index for cancer cells resistant to chemotherapy and histopathological examination was performed on liver sections from different groups.

RESULTS: NDEA significantly disturbed liver functions and most of the aforementioned indices. Treatment with DAS significantly restored liver functions and hepatocellular integrity; improved parameters of energy metabolism and suppressed free-radical generation.

CONCLUSION: We provide evidence that DAS exerts a protective role on liver functions and tissue integrity in face of enhanced tumorigenesis caused by NDEA, as well as improving cancer-cell sensitivity to chemotherapy. This is mediated through combating oxidative stress of free radicals, improving the energy metabolic state of the cell, and enhancing the activity of G6Pase, GST and AR enzymes.

Keywords: N-nitrosodiethylamine; Diallyl sulfide; Liver cancer; Energy metabolism; Aldose reductase