Lycopene and beta-carotene protect in vivo iron-induced oxidative stress damage in rat prostate.

It has been suggested that iron overload may be carcinogenic. In the present study, we evaluated the effect of plasma and prostate carotenoid concentration on oxidative DNA damage in 12-week-old Wistar rats treated with intraperitoneal (ip) ferric nitrilotriacetate (Fe-NTA) (10 mg Fe/kg). Plasma beta-carotene and lycopene concentrations were measured as a function of time after ip injection of carotenoids (10 mg kg(-1) day(-1) beta-carotene or lycopene) in rats. The highest total plasma concentration was reached 3 and 6 h after ip injection of lycopene or beta-carotene, respectively. After 5 days of carotenoid treatment, lycopene and beta-carotene were present in the 0.10-0.51 nmol/g wet tissue range in the prostate. Using a sensitive method to detected 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) by HPLC/EC, the level of 8-oxodGuo in rat prostate DNA was significantly higher (6.3 +/- 0.6 residues/10(6) dGuo) 3 h after Fe-NTA injection compared with control rats (1.7 +/- 0.3 residues/10(6) dGuo). Rats supplemented with lycopene or beta-carotene for 5 days prior to Fe-NTA treatment showed a reduction of about 70% in 8-oxodGuo levels to almost control levels. Compared with control rats, the prostate of Fe-NTA-treated animals showed a 78% increase in malondialdehyde accumulation. Lycopene or beta-carotene pre-treatment almost completely prevented lipid damage. Epidemiological studies have suggested a lower risk of prostate cancer in men reporting a higher consumption of tomato products. However, before associating this effect with tomato sauce constituents, more information is required. The results described here may contribute to the understanding of the protective effects of carotenoids against iron-induced oxidative stress.

Lycopene and ß-carotene protect in vivo iron-induced oxidative stress damage in rat prostate

It has been suggested that iron overload may be carcinogenic. In the present study, we evaluated the effect of plasma and prostate carotenoid concentration on oxidative DNA damage in 12-week-old Wistar rats treated with intraperitoneal (ip) ferric nitrilotriacetate (Fe-NTA) (10 mg Fe/kg). Plasma ß-carotene and lycopene concentrations were measured as a function of time after ip injection of carotenoids (10 mg kg-1 day-1 ß-carotene or lycopene) in rats. The highest total plasma concentration was reached 3 and 6 h after ip injection of lycopene or ß-carotene, respectively. After 5 days of carotenoid treatment, lycopene and ß-carotene were present in the 0.10-0.51 nmol/g wet tissue range in the prostate. Using a sensitive method to detected 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) by HPLC/EC, the level of 8-oxodGuo in rat prostate DNA was significantly higher (6.3 ± 0.6 residues/10(6) dGuo) 3 h after Fe-NTA injection compared with control rats (1.7 ± 0.3 residues/10(6) dGuo). Rats supplemented with lycopene or ß-carotene for 5 days prior to Fe-NTA treatment showed a reduction of about 70 percent in 8-oxodGuo levels to almost control levels. Compared with control rats, the prostate of Fe-NTA-treated animals showed a 78 percent increase in malondialdehyde accumulation. Lycopene or ß-carotene pre-treatment almost completely prevented lipid damage. Epidemiological studies have suggested a lower risk of prostate cancer in men reporting a higher consumption of tomato products. However, before associating this effect with tomato sauce constituents, more information is required. The results described here may contribute to the understanding of the protective effects of carotenoids against iron-induced oxidative stress.

Lycopene inhibits DNA damage and liver necrosis in rats treated with ferric nitrilotriacetate.

Experimental and epidemiological evidence suggests that lycopene, a carotenoid present in tomatoes, tomato products, and several fruits and vegetables, may play a role in preventing certain cancers in humans. We have investigated the effect of lycopene pretreatment on lipid peroxidation, oxidative damage to DNA, and histopathological changes in liver of animals subjected to intraperitoneal (ip) ferric nitrilotriacetate (Fe-NTA) administration. Compared with control rats, liver of Fe-NTA-treated animals showed a significant increase in the 8-oxo-7,8-dihydro-2'-deoxyguanosine level and a 75% increase in malondialdehyde accumulation concomitant with histopathological changes. Five days of lycopene pretreatment (10 mg/kg body weight, ip) almost completely prevented liver biomolecule oxidative damage and protected the tissue against the observed histological alterations.

trans,trans-2,4-decadienal-induced 1,N(2)-etheno-2'-deoxyguanosine adduct formation.

A number of ring-extended DNA adducts resulting from the reaction of alpha,beta-unsaturated aldehydes, or their epoxides, with DNA bases have been characterized in recent years. These adducts may lead to miscoding during DNA replication, resulting, if not repaired, in mutations that can contribute to cancer development. trans,trans-2, 4-Decadienal (DDE) is one of the highly cytotoxic aldehydes endogenously formed from lipid peroxidation. To evaluate its DNA damaging potential, we have investigated the reaction of DDE with 2'-deoxyguanosine (dGuo) in the presence of peroxides. Three stable adducts were isolated by reverse-phase HPLC. Adduct A1, 3-(2-deoxy-beta-D-erythro-pentafuranosyl)-5,9-dihydro-9H-imidazo[2 , 1-i]purin-9-hydroxy, is a tautomer of 1, N(2)-etheno-2'-deoxyguanosine, a well-known reaction product of epoxy aldehydes with dGuo. Two new diasteroisomeric products, A2-1 and A2-2, 1-¿[3-(2'-deoxy-beta-D-erythro-pentafuranosyl)-5, 9-dihydro-9H-imidazo[2,1-i]purin-9-hydroxy]-7-yl¿-2-one-3-octanol, were isolated and characterized on the basis of their spectroscopic features as 1,N(2)-etheno adducts possessing a carbon side chain with a carbonyl and a hydroxyl group. The proposed reaction mechanism for the formation of adducts A2 involves DDE double epoxidation and hydrolysis of the C4 epoxy group prior to nucleophilic addition of the exocyclic amino group of dGuo to C1 of the aldehyde, followed by cyclization via nucleophilic attack on the C2 epoxy group by N-1 and elimination of H(2)O. After treatment of calf thymus DNA with DDE, formation of adducts A1 and A2 was detected by the LC/ESI/MS-MS technique. These results can contribute to a better understanding of the chemical structures of adducts resulting from the reaction of aldehydes with nucleic acid bases, a necessary step in assessing the genotoxic risks associated with this class of compounds.