On the cytotoxicity of chrysotile asbestos fibers toward pulmonary alveolar macrophages. II. Effects of nicotinamide on the cell metabolism.
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.
Nadeau
D
D
Département de biologie, Faculté des sciences, Université de Sherbrooke, Quebec, Canada.
Lane
D A
DA
D000818:Animals; D001194:Asbestos / Q000633:toxicity*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005696:Galactosidases / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007773:Lactates / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D009536:Niacinamide / Q000494:pharmacology*; D009711:Nucleotides / Q000378:metabolism; D010766:Phosphorylation; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism; D011773:Pyruvates / Q000096:biosynthesis; D051381:Rats
D007773:Lactates; D009711:Nucleotides; D011773:Pyruvates; D009243:NAD; D001194:Asbestos; D009536:Niacinamide; D009249:NADP; D007770:L-Lactate Dehydrogenase; D005696:Galactosidases