Effect of S-allylcysteine on oxidant-antioxidant status during N-methyl-N'-nitro-N-nitrosoguanidine and saturated sodium chloride-induced gastric carcinogenesis in Wistar rats.
We investigated the chemopreventive effect of S-allylcysteine (SAC), a water-soluble garlic constituent against gastric carcinogenesis induced in male Wistar rats by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and saturated sodium chloride (S-NaCl). The animals were divided into four groups of six animals. Rats in groups 1 and 2 were administered MNNG (200 mg/kg body weight) on days 0 and 14 as well as S-NaCl (1 mL/rat) three days during weeks 0 to 3, and thereafter placed on basal diet until the end of the experiment. Rats in group 2 in addition received SAC (200 mg/kg body weight) three times per week starting on the day following the first exposure to MNNG and continued until the end of the experimental period. Group 3 animals were given SAC alone as in group 2. Group 4 animals received basal diet and tap water throughout the experiment and served as the untreated control. The animals were sacrificed after an experimental period of 21 weeks. Measurement of lipid peroxidation and antioxidants of the glutathione redox cycle in the stomach tissue, liver and venous blood was used to monitor the chemopreventive potential of SAC. All animals that received MNNG and S-NaCl alone, developed tumours, identified histologically as squamous cell carcinomas. In the tumour tissue, diminished lipid peroxidation was accompanied by increase in reduced glutathione (GSH) and GSH-dependent enzymes, whereas in the liver and circulation, enhanced lipid peroxidation was associated with antioxidant depletion. Administration of SAC suppressed the incidence of MNNG+S-NaCl-induced gastric tumours as revealed by the absence of carcinomas. SAC ameliorated MNNG-induced decreased susceptibility of the gastric mucosa to lipid peroxidation, whilst simultaneously increasing the antioxidant status. In the liver and blood, SAC reduced the extent of lipid peroxidation and significantly enhanced antioxidant activities. We suggest that SAC exerts its chemopreventive effects by modulating lipid peroxidation and enhancing GSH-dependent antioxidants in the target organ as well as in the liver and blood.
Velmurugan
Balaiya
B
Department of Biochemistry Faculty of Science, Annamalai University, Annamalainagar-608 002, Tamil Nadu, India.
Bhuvaneswari
Vaidhyanathan
V
Nagini
Siddavaram
S
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008769:Methylnitronitrosoguanidine; D016877:Oxidants / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism
D000970:Antineoplastic Agents; D000975:Antioxidants; D014408:Biomarkers, Tumor; D016877:Oxidants; D008769:Methylnitronitrosoguanidine; D012965:Sodium Chloride; C065299:S-allylcysteine; D005978:Glutathione; D003545:Cysteine