Polymorphisms of 5,10-methylenetetralydrofolate reductase (MTHFR), fruit and vegetable intake, and the risk of stomach cancer.

Stomach cancer is a serious public health problem in China. 5,10-Methylenetetralydrofolate reductase (MTHFR) may be involved in both DNA methylation and DNA synthesis. Folate deficiency is associated with cancer risk that may be modulated by a genetic variation in the MTHFR gene in folate metabolism. The main goal of this study was to evaluate the association between polymorphisms of the MTHFR gene and the risk of stomach cancer. This study also explored the modification effects of fruit and vegetable intake (one of the main constituents is folate) on the risk of this disease. A population-based case-control study was conducted in Taixing, China, consisting of 206 newly diagnosed cases with primary stomach cancer and 415 healthy population controls. Polymorphisms of MTHFR C677T and A1298C were assayed by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) techniques. The data were analysed using the logistic regression model. No obvious association between the MTHFR A1298C polymorphism and the risk of stomach cancer was observed in this study. The frequencies of 677 C/C, C/T, and T/T were 34.5, 50.9, and 14.6%, respectively, in controls. The frequency of the MTHFR 677 wild homozygotic genotype was 25.8% in cases, which was lower than that in controls (34.5%). The adjusted odds ratio (OR) for the MTHFR 677 any T genotype was 2.05 (95% confidence interval (CI), 1.26-3.34) when compared with the C/C genotype. In the low fruit and vegetable intake group an increasing trend was observed with the T allele exposure, p = 0.0056. The adjusted ORs were 1.68 (95% CI = 0.86-3.29) for the C/T genotype and 3.58 (95% CI = 1.46-8.75) for the T/T genotype, respectively. The MTHFR 677 any T genotype was associated with an increased risk of primary stomach cancer among the Chinese population. Folate deficiency might modify the MTHFR gene polymorphism and influence the risk of stomach cancer.

[Studies on protective effect of total flavonoids of Astragalus on liver damage induced by paracetamol].

OBJECTIVE: To study the protective effect of total flavonoids of Astragalus (TFA) on the liver against large doses of paracetamol in mice. METHOD: After oral administration of TFA or Vitamin C 1 h prior to giving large dose of paracetamol in mice, the changes of paracetamol-induced mortality rate, serum enzyme level and liver damage degree were observed. RESULT: Paracetamol produced 80% mortality, within 24 hours of the administration of a dose of 1000 mg.kg-1 to the mice. Pre-treatment of the animals with TFA (100 mg.kg-1) or Vitamin C (1,000 mg.kg-1) reduced the death rate to 20% and 0% respectively. There was also a significant rise in the serum enzyme level of alanine transaminase (P < 0.001) and the area of liver necrosis (P < 0.001), 24 h after paracetamol (400 mg.kg-1) treatment. With pre-treatment with either TFA or Vitamin C, there was an obvious dose-dependent decrease in ALT levels and the area of hepatocellular necrosis. CONCLUSION: TFA has potential protecting effect against the paracetamol-induced hepatic damage.

[Protection against paracetamol-induced hepatic damage using total flavonoids of Astragalus].

OBJECTIVE: To study the mechanism of the protection by total flavonoids of Astragalus protection against paracetamol-induced hepatic damage. METHOD: Analysing paracetamol and its metabolites in mice urine by HPLC and studying the mechanism of anti-damage induced by paracetamol using experiment module of pentobarbital-induced sleeping time. RESULT: Administration of large doses of paracetamol to C57BL/6J mice produced significant hepatic injury with marked elevation in serum ALT activity and severe hepatocellular necrosis. TFA showed a good protective capability against paracetamol-induced hepatic injury. TFA had no marked effect on paracetamol and its metabolites except for the mercapturate-conjugate. The concentration of mercapturate change decreased with increasing TFA dose. TFA had no effect on the pentobarbital metabolites (P > 0.05). However, paracetamol (400 mg.kg-1) prolonged the sleeping time (by 110 min relative to the controls, P < 0.001). The TFA (P < 0.005) caused significant reduction in paracetamol-prolonged pentobarbital-induced sleep. CONCLUSIONS: The mechanism of TFA's protective effect against the paracetamol-induced damage may be related to the inhibition of some metabolism progress of paracetamol and the reduction of the toxicity metabolite such as mercapturate-conjugate.