title: Protective effects of garlic oil on hepatocarcinoma induced by N-nitrosodiethylamine in rats.
abstract: To investigate the protective effects and the possible mechanisms of garlic oil (GO) against N-nitrosodiethylamine (NDEA)-induced hepatocarcinoma in rats, Wistar rats were gavaged with GO (20 or 40 mg/kg) for 1 week, and then were gavaged with GO and NDEA (10 mg/kg) for the next 20 weeks. The changes of morphology, histology, the biochemical indices of serum, and DNA oxidative damage of liver were examined to assess the protective effects. Lipid peroxidation (LPO), antioxidant defense system, and apoptosis-related proteins were measured to investigate potential mechanisms. At the end of the study (21 weeks), GO administration significantly inhibited the increase of the nodule incidence and average nodule number per nodule-bearing liver induced by NDEA, improved hepatocellular architecture, and dramatically inhibited NDEA-induced elevation of serum biochemical indices (alanine aminotransferase , aspartate aminotransferase, alkaline phosphatase and gamma-glutamyl transpeptidase) and hepatic 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in a dose-dependent manner. The mechanistic studies demonstrated that GO counteracted NDEA-induced oxidative stress in rats illustrated by the restoration of glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST) levels, and the reduction of the malondialdehyde (MDA) levels in liver. Furthermore, the mRNA and protein levels of Bcl-2, Bcl-xl, andβ-arrestin-2 were significantly decreased whereas those of Bax and caspase-3 were significantly increased. These data suggest that GO exhibited significant protection against NDEA-induced hepatocarcinogenesis, which might be related with the enhancement of the antioxidant activity and the induction of apoptosis.
authors.affiliation: Institute of Toxicology, School of Public Health, Shandong University, Jinan, PR China.
authors.forename: Cui-Li
authors.initials: CL
authors.lastname: Zhang
authors.forename: Tao
authors.initials: T
authors.lastname: Zeng
authors.forename: Xiu-Lan
authors.initials: XL
authors.lastname: Zhao
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Yu
authors.forename: Zhen-Ping
authors.initials: ZP
authors.lastname: Zhu
authors.forename: Ke-Qin
authors.initials: KQ
authors.lastname: Xie
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000498:Allyl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D051017:Apoptosis Regulatory Proteins / Q000032:analysis; D015415:Biomarkers; D001835:Body Weight / Q000187:drug effects; D003314:Corn Oil / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D004052:Diethylnitrosamine / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor; D020869:Gene Expression Profiling; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010088:Oxidoreductases / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000498:Allyl Compounds; D016588:Anticarcinogenic Agents; D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; D013440:Sulfides; D004052:Diethylnitrosamine; C038491:allyl sulfide; D003314:Corn Oil; D000080242:8-Hydroxy-2'-Deoxyguanosine; D010088:Oxidoreductases; D003849:Deoxyguanosine