Borg-Neczak K, Tjälve H
Swedish University of Agricultural Sciences, Faculty of Veterinary Medicine, Department of Pharmacology and Toxicology, Biomedicum, Uppsala.
Arch Toxicol. 1994;68(7):450-8. doi: 10.1007/s002040050096.
Oral administration of sodium pyridinethione together with Ni2+ (using 63Ni2+ as a tracer) to rats, ferrets and guinea-pigs produced highly increased tissue levels of the metal in several tissues in comparison with animals given the Ni2+ alone. Ni2+ forms a lipophilic complex with pyridinethione and it can be assumed that a facilitated passage of the Ni2+ across the cellular membranes of various tissues is important for the observed effects. Pigmented tissues (e.g. the eye melanin), the pancreatic islets, the nervous system and striated muscles showed high levels of Ni2+ in animals given sodium pyridinethione. However, in some instances marked species differences were observed. Thus, microautoradiography indicated an uptake of Ni2+ both in the beta- and alpha-cells in the pancreatic islets in the rat, whereas in the guinea-pig only some cells (probably the alpha-cells) accumulated high levels of Ni2+. In the ferret sodium pyridinethione induced a high uptake of Ni2+ in the heart muscle, which was not seen in the other species. The Ni2+ is probably taken up in the various tissues complexed to pyridinethione. Within the tissues the complex may dissociate and the Ni2+ may bind to some endogenous tissue components. The affinity of the Ni2+ for the endogenous ligands in relation to the affinity for the pyridinethione may be of importance for the effects on the disposition of the Ni2+. The species variations may be related to differences in the structural conformations of the endogenous Ni(2+)-binding ligands.
给大鼠、雪貂和豚鼠经口给予吡啶硫酮钠并同时给予Ni2+（使用63Ni2+作为示踪剂），与仅给予Ni2+的动物相比，几种组织中的金属组织水平大幅升高。Ni2+与吡啶硫酮形成亲脂性复合物，可以推测，Ni2+跨各种组织细胞膜的易化转运对于所观察到的效应很重要。在给予吡啶硫酮钠的动物中，色素沉着组织（如眼黑色素）、胰岛、神经系统和横纹肌显示出高水平的Ni2+。然而，在某些情况下观察到了明显的物种差异。因此，显微放射自显影显示大鼠胰岛的β细胞和α细胞都摄取了Ni2+，而在豚鼠中只有一些细胞（可能是α细胞）积累了高水平的Ni2+。在雪貂中，吡啶硫酮钠诱导心肌对Ni2+的高摄取，这在其他物种中未见。Ni2+可能以与吡啶硫酮复合的形式被各种组织摄取。在组织内，复合物可能解离，Ni2+可能与一些内源性组织成分结合。Ni2+对内源性配体的亲和力相对于对吡啶硫酮的亲和力可能对Ni2+处置的影响很重要。物种差异可能与内源性Ni(2+)结合配体的结构构象差异有关。
