Abstract:
Fluoroquinolones are a widely used class of chemotherapeutics within veterinary medicine, prized for their broad-spectrum bactericidal activity. These drugs present a known risk of retinal phototoxicity in domestic cats (Felis catus); therefore, using lower doses and alternative antibiotic classes is encouraged in this species. This adverse drug effect of fluoroquinolones, and enrofloxacin specifically, has been determined to be species-specific in domestic felids. Four feline-specific missense variants in ABCG2 result in four amino acid changes (E159M, S279L, H283Q, and T644I) that are unique to the domestic cat compared with multiple other nonfeline mammalian species. These changes alter the ABCG2 protein involved with the cellular transmembrane transport of drugs, including fluoroquinolones, making the protein functionally defective in domestic cats. The predisposition to fluoroquinolone-mediated phototoxicity in nondomestic felids was explored in this study. At least eight nondomestic felids share the four ABCG2 missense variants with domestic cats, and eleven other felids shared at least three of the four domestic cat variants. Taken together, these results suggest the genetic potential for nondomestic felids to also experience fluoroquinolone-induced retinal phototoxicity; therefore, cautions similar to those for domestic cats should be followed for these drugs in the entire feline taxon.
摘要:
氟喹诺酮类药物是兽医学中广泛使用的一类化学治疗剂,因其广谱杀菌活性而备受赞誉。这些药物在家猫(Feliscatus)中存在已知的视网膜光毒性风险;因此,在该物种中,鼓励使用较低剂量和替代抗生素类别。氟喹诺酮类药物的这种不良反应,特别是恩诺沙星,已被确定为在国内猫科动物中具有物种特异性。ABCG2中的四个猫特异性错义变体导致四个氨基酸变化(E159M,S279L,H283Q,和T644I)与其他多种非猫科动物相比,是家猫特有的。这些变化改变了与药物的细胞跨膜转运有关的ABCG2蛋白,包括氟喹诺酮类药物,使蛋白质在家猫中功能缺陷。本研究探讨了非家养动物对氟喹诺酮介导的光毒性的易感性。至少有八个非家猫与家猫共享四个ABCG2错义变体,和其他11个猫科动物至少分享了4种家猫变种中的3种。一起来看,这些结果表明,非家养动物也具有经历氟喹诺酮诱导的视网膜光毒性的遗传潜力;因此,在整个猫科动物分类群中,这些药物应遵循与家猫相似的注意事项。