• The Korean Journal of Pharmacology
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• v.32 no.3
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• pp.407-416
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• 1996

The reactive intermediates formed during the metabolism of therapeutic agents, toxicants and carcinogens by cytochromes P450 are frequently capable of covalently binding to tissue macromolecules and causing tissue damage. It has been shown that YH439, a congener of malotilate, is effective in suppressing hepatic P450 2E1 expression. The present study was designed to further establish the mechanistic basis of YH439 protection against toxicant by assessing its effects against chemical-mediated potentiated hepatotoxicity. Retinoyl palmitate (Vit-A) pretreatment of rats for 7 days substantially enhanced carbon tetrachloride hepatotoxicity, as supported by an ${\sim}5-fold$ increase in serum alanine aminotransferase (ALT) activity, as compared to $CCl_4$ treatment alone. The elevation of ALT activity due to Vit-A was completely blocked by the treatment of $GdCl_3$ a selective inhibitor of Kupffer cell activity. Concomitant pretreatment of rats with both YH439 and Vit-A resulted in a 94% decrease in Vit-A-potentiated $CCl_4$ hepatotoxicity. YH439 was also effective against propyl sulfide-potentiated $CCl_4-induced$ hepatotoxicity. Whereas propyl sulfide (50 mg/kg, 7d) enhanced $CCl_4-induced$ hepatotoxicity by >5-fold, relative to $CCl_4$ treatment alone, concomitant treatment of animals with both propyl sulfide and YH439 at the doses of 100 and 200 mg/kg prevented propyl sulfide-potentiated $CCl_4$ hepatotoxicity by 35% and 90%, respectively. Allyl sulfide, a suppressant of hepatic P450 2E1 expression, completely blocked the propyl sulfide-enhanced hepatotoxicity, indicating that propyl sulfide potentiation of $CCl_4$ hepatotoxicity was highly associated with the expression of P450 2E1 and that YH439 blocked the propyl sulfide-enhanced hepatotoxicity through modulation of P450 2E1 levels. Propyl sulfide- and $CCl_4-induced$ stimulation of lipid peroxidation was also suppressed by YH439 in a dose-related manner, as supported by decreases in malonedialdehyde production. The role of P450 2E1 induction in the potentiation of $CCl_4$ toxicity and the effects of YH439 were further evaluated using pyridine as a P450 2E1 inducer. Pyridine pretreatment substantially enhanced the $CCl_4$ hepatotoicity by 23-fold, relative to $CCl_4$ alone. YH439, however, failed to reduce the pyridine-potentiated toxicity, suggesting that the other form(s) of cytochroms P450 inducible by pyridine, but not suppressible by YH439 treatment, may play a role in potentiating $CCl_4-induced$ hepatotoxicity. YH439 was capable of blocking cadmium chloride-induced liver toxicity in mice. These results demonstrated that YH439 efficiently blocks Vit-A-enhanced hepatotoxiciy through Kupffer cell inactivation and that the suppression of P450 2E1 expression by YH439 is highly associated with blocking of propyl sulfide-mediated hepatotoxicity.

• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.9
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• pp.1148-1160
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• 2007

This study was performed to document the association between eating behaviors and major risk factors for cardiovascular diseases. Those who stated that they ate a daily breakfast for male and female were 88.6% and 96.0%, $1{\sim}2$ times a week were 9.1% and 2.0%, $3{\sim}4$ times a week were 2.3% and 2.0%, respectively. Those who stated that they were overeating of $0{\sim}1$ time a week for man and female were 80.7% and 89.9%, overeating of $2{\sim}3$ times a week were 19.3% and 10.1%, respectively. Those who said that they were regular of meal time for man and female were 38.6%, and 37.4%, sometimes irregular of meal time were 14.8% and 19.2%, irregular of meal time were 46.6% and 43.4%, respectively. Those who said that they were light of eating volume for man and female were 20.5% and 25.3%, moderate of eating volume were 69.3% and 61.6%, heavy of eating volume were 10.2% and 13.1%, respectively. Those who said that they were very fast of eating speed for man and female were 15.9% and 8.1%, fast of eating speed were 51.1% and 34.3%, moderate of eating speed were 4.5% and 20.2%, slow of eating speed were 17.0% and 14.1%, and very slow of eating speed were 11.4% and 23.2%, respectively. Higher frequency of breakfast a week resulted in higher serum total cholesterol and blood sugar for the daily eating group for both genders with women having high LDL-cholesterol and HDL-cholesterol. Both group had high HDL-cholesterol and low blood sugar with less number of overeating, with men having low triglyceride and LDL-cholesterol. With regular meal, both group had low triglyceride, total-cholesterol, atherogenic index, and blood sugar with women having low LDL-cholesterol. For both groups, the triglyceride, total-cholesterol, LDL-cholesterol, atherogenic index, and blood sugar had higher figures for overeating, with men having low HDL-cholesterol and women having high HDL-cholesterol. This study revealed that less number of overeating, regular mealtime, and less volume of food intake are effective in preventing and treating for the cardiovascular diseases.