Inhibitory Effects of S‐Methylcysteine and Cysteine on the Promoting Potential of Sodium Phenobarbital on Rat Liver Carcinogenesis

Abstract

The effects of S-methylcysteine (SMC) and cysteine on the promotion stages of rodent hepatocarcinogenesis in a medium-term bioassay previously developed by Ito were examined. Initiation was induced by a single dose of diethylnitrosamine (DEN), followed by dietary administration of the promoter sodium phenobarbital (NaPB) 2 weeks later, for 6 weeks. Partial hepatectomy was conducted on all the animals at week 3. Inhibitory potential was evaluated by analyzing two markers of carcinogenesis, namely numbers of glutathione S-transferase placental form (GST-P)-positive foci, and proliferating cell nuclear antigen (PCNA). In addition, the level of ornithine decarboxylase (ODC), one of the rate-limiting enzymes of polyamine metabolism induced by promoters, was analyzed. SMC and cysteine induced significant reduction in the areas of GST-P-positive foci. A significant reduction in the PCNA index was observed in the entire liver as well as in GST-Ppositive areas. SMC also induced down-regulation of the ODC enzyme activity. Thus, SMC and cysteine were found to inhibit the promotion stage of DEN-induced hepatocarcinogenesis. No cocarcinogenic effects were evident on administration of either of these chemicals with NaPB.

Prevention of hepatocarcinogenesis with phosphatidylcholine and menaquinone-4: In vitro and in vivo experiments

“…On average, absolute liver weights and relative liver weights (liver weight/body weight) in groups B, C, and D, all receiving diets containing PB, were greater than in other groups (18.9 vs 16.7 g and 0.0347 vs 0.0301 g/g). We noted that the carcinogenesis promoter PB, a potent mitogen in hepatocytes, increased cell cycling within GST-P-positive foci resulting in hypertrophy and/or hyperplasia [21,23].…”

“…Accordingly, we initiated hepatocarcinogenesis with DEN enhanced by coadministration with phenobarbital (PB) [21,22] in rats subsequently treated with PC and MK-4. Immunohistochemical morphometric analysis was directed at glutathione S-transferase (GST-P), a marker for preneoplastic change in hepatocytes [23] that has become established in quantitative analysis of the process of hepatocarcinogenesis in rats [21,[24][25][26]. Some papers reported PC had protection potential toward liver injury by CCL4 [27,28].…”

S-Methylcysteine (SMC) Ameliorates Intestinal, Hepatic, and Splenic Damage Induced by Cryptosporidium parvum Infection Via Targeting Inflammatory Modulators and Oxidative Stress in Swiss Albino Mice

“…Interestingly, several previous reports have documented a wide range of activities of garlic and its components, particularly SMC, for treatment of various physiological and pathological conditions [ 24 , 25 , 26 ]. In this regard, some previous reports revealed that garlic, SMC, and other organosulfur compounds of raw or extracted garlic showed anticancer [ 27 ], antioxidant [ 28 ], anti-inflammatory [ 29 ], antidiabetic [ 30 ], cardioprotective [ 24 ], neuroprotective [ 31 ], hypocholesterolemic [ 30 ], antiinfective [ 32 , 33 ], and hepatoprotective effects [ 34 , 35 , 36 ]. To the authors’ knowledge, no former investigations assessed the effect of SMC against C. parvum either in vitro or in vivo.…”

Differences in Sensitivity of F344 Rats from Different Breeders to Phenobarbital Hepatocarcinogenicity

“…animals 6,17,23 . Using rats from Japan Charles River Co., it is well known that numbers and areas per cm 2 of GST-P positive foci in the liver in the Ito test are increased significantly in PB treated rats compared with control groups given DEN alone 7,[14][15][16][17][18][24][25][26][27] . According to those studies, the number of GST-P positive foci in the liver of control groups ranged from 3.6 ± 1.8 to 5.8 ± 2.4; the area of GST-P positive foci in the livers of control groups ranged from 0.24 ± 0.23 to 0.56 ± 0.35; the number of GST-P positive foci in the livers of PB-treated groups ranged from 7.2 ± 2.8 to 13.9 ± 2.9; and the area of GST-P positive foci in the livers of PBtreated groups ranged from 0.94 ± 0.61 to 1.76 ± 0.74.…”

“…We compared these rats for hepatocarcinogenic effects of PB, using a medium-term rat liver bioassay system, the Ito test 5,6,12,13 . PB has been used as a positive carcinogen control [14][15][16][17] , and to examine the dispersion of effects among animals from different breeders is useful.…”