Dietary folate protects against azoxymethane-induced aberrant crypt foci development and oxidative stress in rat colon

Abstract

Azoxymethane (AOM) induces cancer and oxidative stress in rat colon. This study tested the hypothesis that dietary folate supplementation protects against AOM-induced oxidative stress and reduces aberrant crypt foci (ACF) development in rat colon. Fifty-four weanling male albino rats, with an average body weight of 50 ± 5 g, were randomly divided into three groups – A, B and C (18 rats per group) – and fed 2, 8 or 40 mg of folic acid per kg of supplemented diets, respectively, throughout the eight weeks' experimental period. The animals were supplied with diet and water ad libitum for four weeks and they reached an average body weight of 100 g. Thereafter each group was then further randomly subdivided into three subgroups (six rats per subgroup): control, vehicle and AOM-injected groups. The control group did not receive any treatment (neither AOM injection nor saline), the rats in the vehicle group were given 1 mL intraperitoneal injection of saline once a week for two weeks and the rats in the AOM-injected group were given two intraperitoneal injections of AOM dissolved in saline once a week for two weeks totaling 30 mg/kg body weight. After the last AOM injection, animals were continuously fed ad libitum their specified diet for two weeks of last AOM injection, all rats were sacrificed, and colon tissues were collected and used for ACF enumeration and measurements of glutathione (GSH) and total antioxidant capacity (TAC). The results revealed that AOM-injected rats showed lower levels of GSH and TAC as compared with control and vehicle groups. Folic acid-supplemented diets suppressed the AOM-induced ACF and GSH depletion in a dose-dependent manner and augmented the TAC. It was concluded that folic acid supplementation protects against the AOM-induced ACF formation by suppressing the AOM-induced GSH depletion in rat colon cells.