Nadeau D, Lane D A
Département de biologie, Faculté des sciences, Université de Sherbrooke, Quebec, Canada.
Toxicol Appl Pharmacol. 1989 Mar 15;98(1):144-58. doi: 10.1016/0041-008x(89)90142-7.
Since it was recently shown that the addition of nicotinamide (NAM) to pulmonary alveolar macrophages (PAM) cell monolayers significantly altered their ATP pools (Nadeau and Lane, 1988), the effects of the vitamin on the metabolism of the cells, exposed or not to very short chrysotile asbestos fibers (VSF), were evaluated. First, it was found that the addition of NAM to the culture medium caused a dose-dependent (5-30 mM) decrease in the extracellular liberation of lactate and pyruvate by PAM. This is suggestive of a direct effect of NAM on the metabolism of glucose. A decrease in extracellular lactate was also observed when control PAM were exposed to 50 micrograms of VSF asbestos. This latter effect was however progressively abolished when the NAM was added to the asbestos-exposed cell monolayers. Second, contrary to the lactic acid production, the exposure to chrysotile caused an increase in the extracellular liberation of pyruvate by PAM. This cell response to the asbestos fibers could represent an antioxidative defense mechanism. Yet, interestingly enough, this effect of the VSF on PAM was not suppressed by the presence of the vitamin. The NAM also induced a dose-dependent decrease in the total lactate dehydrogenase content of PAM monolayers. By comparison, 3-aminobenzamide (up to 5 mM) did not appreciably modify these parameters. After an 18-hr incubation period with 20 mM NAM, the NAD+ pools of control PAM increased by approximately 300% comparatively to a approximately 40% increase for the NADP+ content. The exposure to the VSF asbestos caused a dose-dependent depletion of the cellular NAD+ and NADH pools. However, for the latter, the vitamin prevented the depletion effect of the asbestos fibers. Comparatively, the NADP(H) pools increased. This shift toward the phosphorylated pyridine nucleotide forms could also represent a defense of the cell against the oxygen radicals produced during the ingestion of the fibers. Overall, it is shown that changes in the energy metabolism could be implicated in the toxicity of chrysotile asbestos fibers toward PAM, and that the cells seem to be able to respond to an oxidant stress. Although not fully elucidated at the present time, these data tend nonetheless to point out that the protective effect of NAM could involve some modifications of the host defenses against prooxidants.
由于最近研究表明，向肺泡巨噬细胞（PAM）单层细胞中添加烟酰胺（NAM）会显著改变其ATP储备（Nadeau和Lane，1988年），因此评估了该维生素对暴露或未暴露于极短温石棉纤维（VSF）的细胞代谢的影响。首先，发现向培养基中添加NAM会导致PAM细胞外乳酸和丙酮酸释放量呈剂量依赖性（5-30 mM）下降。这表明NAM对葡萄糖代谢有直接影响。当对照PAM暴露于50微克VSF石棉时，细胞外乳酸也出现下降。然而，当向暴露于石棉的细胞单层中添加NAM时，后一种效应逐渐消失。其次，与乳酸产生情况相反，温石棉暴露导致PAM细胞外丙酮酸释放增加。这种细胞对石棉纤维的反应可能代表一种抗氧化防御机制。然而，有趣的是，VSF对PAM的这种作用并未因维生素的存在而受到抑制。NAM还导致PAM单层细胞中总乳酸脱氢酶含量呈剂量依赖性下降。相比之下，3-氨基苯甲酰胺（高达5 mM）对这些参数没有明显影响。在与20 mM NAM孵育18小时后，对照PAM的NAD+储备相对增加了约300%，而NADP+含量增加了约40%。VSF石棉暴露导致细胞NAD+和NADH储备呈剂量依赖性消耗。然而，对于后者，维生素可防止石棉纤维的消耗作用。相比之下，NADP（H）储备增加。这种向磷酸化吡啶核苷酸形式的转变也可能代表细胞对纤维摄取过程中产生的氧自由基的一种防御。总体而言，研究表明能量代谢变化可能与温石棉纤维对PAM的毒性有关，并且细胞似乎能够对氧化应激作出反应。尽管目前尚未完全阐明，但这些数据仍倾向于指出，NAM的保护作用可能涉及宿主对促氧化剂防御的一些改变。
