[Toxicologic and nutritional aspects of nitrates and nitrites].

G de Saint-Blanquat
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Abstract

The toxic action of nitrates and nitrites has often been summarized by methemoglobinemia and nitrosation of amines inducing carcinogenic effects; these two impacts are spectacular, but they hide varying more or less insidious actions recently studied and perceived. In the NO3/NO2 couple, it is accepted that especially nitrite ion lays down a toxicological problem, probably because of its particular chemical reactivity: nitrite ion, which is the base of nitrous acid HNO2 (pKa = 3.36) can react with many functional groups from dietary or endogenous origin; it is also a reducing agent, only oxidable by chemical oxidants or adequate enzyme systems; at the same time it is an oxidant for many reduced substrates. These different possibilities explain the chemical complexity of these compounds and almost their reactivity in biological various media with toxicological implications (modification of the redox state). In man, the presence of nitrates in the digestive tract may result in nitrite formation, because nitrate-reductase from bacterial or enterocyte origin; more particularly in stomach, nitrites are characterized by a great instability imputable to the low pH of gastric juice and to secreted factors which accelerate phenomena; at the same time, nitrates and nutrites exercise opposite effects on gastric secretion (volume, acidity, pepsin) and on gastric mucosal irrigation: while nitrates increase these different parameters, nitrites reduce secretory activity but correlations between secretion and irrigation show that nitrates induce a deep modification of hydric compartment whereas nitrites rather react through cellular anoxy. In intestine, nitrates and chiefly nitrites are very quickly absorbed by a passive mechanism and they are characterized by an extrahepatic cycle; nitrates and nitrites are also eliminated in large quantities by kidneys, and nitrates have a very high diuretic effect: these NO3- ions move Cl- ions, inducing a Na+ waste, a decrease in extracellular space and an alkalosis; this diuretic action of ionic origin is moreover increased by a rise in glomerular blood flow facilitating filtration; these compounds therefore present vasomotor effects, probably by an action on catecholamines whose metabolism is modified. Last, nitrates are suspected to be responsible for reproduction troubles, thyroid dysfunction, perturbances of vitamins availability and nutritional effects. Most of the impacts of nitrates and nitrites are now well known, but their cellular of molecular action is not clear, and as a result there is a suspicion in regard to these products very widely present in food.

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[硝酸盐和亚硝酸盐的毒理学和营养学方面]。
硝酸盐和亚硝酸盐的毒性作用通常被概括为高铁血红蛋白血症和亚硝化引起的致癌作用;这两种影响是惊人的,但它们隐藏着最近研究和感知到的各种或多或少阴险的行为。在NO3/NO2对中,特别是亚硝酸盐离子存在一个毒理学问题,这可能是由于其特殊的化学反应性:亚硝酸盐离子作为亚硝酸HNO2 (pKa = 3.36)的碱,可以与许多来自膳食或内源的官能团发生反应;它也是还原剂,只能被化学氧化剂或适当的酶系统氧化;同时,它也是许多还原底物的氧化剂。这些不同的可能性解释了这些化合物的化学复杂性,以及它们在具有毒理学意义的各种生物介质中的反应性(氧化还原状态的修饰)。在人类中,消化道中硝酸盐的存在可能导致亚硝酸盐的形成,因为来自细菌或肠细胞的硝酸盐还原酶;特别是在胃中,亚硝酸盐具有很大的不稳定性,这可归因于胃液的低pH值和加速现象的分泌因子;同时,硝酸盐和营养物质对胃液分泌(体积、酸度、胃蛋白酶)和胃粘膜灌洗产生相反的影响:硝酸盐增加了这些不同的参数,而亚硝酸盐降低了分泌活性,但分泌和灌洗之间的相关性表明,硝酸盐诱导了水腔的深度改变,而亚硝酸盐则通过细胞缺氧发生反应。在肠道中,硝酸盐和主要的亚硝酸盐通过一种被动机制被迅速吸收,它们的特点是肝外循环;硝酸盐和亚硝酸盐也被肾脏大量清除,硝酸盐具有非常高的利尿作用:这些NO3-离子移动Cl-离子,诱导Na+浪费,细胞外空间减少和碱中毒;此外,这种离子源利尿作用因肾小球血流量的增加而增加,从而促进滤过;因此,这些化合物可能通过作用于代谢被改变的儿茶酚胺而表现出血管舒缩作用。最后,硝酸盐被怀疑是造成生殖障碍、甲状腺功能障碍、维生素可用性紊乱和营养影响的原因。硝酸盐和亚硝酸盐的大部分影响现在已经为人所知,但它们的细胞或分子作用尚不清楚,因此人们对这些广泛存在于食品中的产品持怀疑态度。
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[Mechanism of action of mycotoxins]. "Science of Foods" meeting of the French Nutrition Association. Paris-27-28 September 1979. Abstracts. [Free polyunsaturated fatty acids, estrogens and fetoproteins]. [Structure and characterization of the principal constituents of dietary fiber]. [Study of the metabolism of fatty acids and total plasma lipids, and platelet aggregation of a population of elderly men using a diet enriched in gamma-linolenic acid].
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