Diallyl Sulfide Inhibits Lipid Peroxidation by increasing Superoxide dismutase and Glutathione S Transferase Gene Expression in the Liver of Male Sprague Dawley Rats.

Diethylstilbestrol (DES), a synthetic estrogen, is associated with liver cancer in rats and humans. DES undergoes redox cycling producing free radicals which can react with lipids causing lipid peroxidation. Lipid peroxides causes DNA damage, mutations and ultimately cancer. Dially sulfide has been shown to inhibit various types of cancers presumably by metabolic modulation. We hypothesize that DAS will inhibit lipid peroxidation by increasing gene expression of superoxide dismutase (SOD) and Glutathione S Transferase (GST) in the liver of male Sprague Dawley rats. To test this hypothesis four groups of five male Sprague Dawley rats were treated as follows: (1) control (corn oil), (2) 50 mg/kg DAS (3) 50 mg/kg DES, (4) 50 mg/kg DAS, 50mg/kg DES. RNA was extracted from the liver using the trizol. SOD and GST gene expression was assed by real time RT‐PCR. The Folch Method was used to extract lipids from the liver and lipid peroxidation was determined by PeroxiDirect Kit, (Sigma). Animals treated with DES resulted in lipid peroxide formation of 14.5 nmoles/gram of tissue. Co‐administration of DAS and DES attenuated DES‐induced lipid peroxidation by 90%. No lipid peroxides were detected in the control and the DAS treated animals. DES, DAS and a combination of DES and DAS resulted in increases of SOD expression by 2.2, 10.1 and 18.1 fold respectively. Similar results were seen with GST. DES, DAS, and a combination of DES and DAS resulted in GST expression of 0.78, 8.1, and 13.2 fold respectively. Our results demonstrate that DAS inhibits DES induce lipid peroxidation. These data suggest that diallyl sulfide may prevent DES induced cancer and be used to develop potent chemopreventive compounds. Supported in part by NIH grantsRR08111 and RR03020.