Meza Graciela, Aguilar-Maldonado Beatriz
Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México D.F., Mexico.
Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México D.F., Mexico.
Comp Biochem Physiol C Toxicol Pharmacol. 2007 Jul-Aug;146(1-2):203-206. doi: 10.1016/j.cbpc.2006.08.006. Epub 2006 Sep 3.
Streptomycin is the antibiotic of choice to treat tuberculosis and other infectious diseases but it causes vestibular malfunction and hipoacusia. Rodents are usually employed as models of drug action to the inner ear and results are extrapolated to what happens in humans. In rats, streptomycin destroys macular sensory cells and does not affect cochlear ones, whereas in guinea pigs the contrary is true. Action on the vestibular cristae cells involved in vestibulo-ocular reflex integrity is less clear. Thus, we compared this response in both pigmented guinea pigs (Cavia cobaya) and rats (Rattus norvegicus) after parallel streptomycin chronic treatment. In guinea pigs, the reflex was obliterated along treatment time; in rats this behavior was not observed, suggesting that the end organ target was diverse. In recent studies, streptidine, a streptomycin derivative found in the blood of humans and rats treated with streptomycin, was the actual ototoxic agent. The putative streptomycin vestibular organ target observed in humans corresponds with the guinea pig observations. Results observed in rats are controversial: streptidine did not cause any damage either to vestibular cristae nor auditory cells. We hypothesize differential drug metabolism and distribution and conclude that results in laboratory animals may not always be applicable in the human situation.
链霉素是治疗结核病和其他传染病的首选抗生素,但它会导致前庭功能障碍和听力减退。啮齿动物通常被用作内耳药物作用的模型,研究结果会外推至人类情况。在大鼠中,链霉素会破坏黄斑感觉细胞,而不影响耳蜗细胞,而在豚鼠中情况则相反。链霉素对参与前庭眼反射完整性的前庭嵴细胞的作用尚不清楚。因此,我们比较了经平行链霉素慢性治疗后,有色豚鼠(豚鼠)和大鼠(褐家鼠)的这种反应。在豚鼠中,随着治疗时间的推移,反射消失;在大鼠中未观察到这种行为,这表明终末器官靶点不同。在最近的研究中,链霉胍是在接受链霉素治疗的人类和大鼠血液中发现的一种链霉素衍生物,它才是实际的耳毒性药物。在人类中观察到的推测性链霉素前庭器官靶点与豚鼠的观察结果一致。在大鼠中观察到的结果存在争议:链霉胍对前庭嵴和听觉细胞均未造成任何损伤。我们推测药物代谢和分布存在差异,并得出结论,实验室动物的研究结果可能并不总是适用于人类情况。