FK506, a calcineurin inhibitor, prevents cadmium-induced testicular toxicity in mice.

摘要: Cadmium, a ubiquitous environmental contaminant, damages several major organs in humans and other mammals. The molecular mechanisms for damage are not known. At high doses (5 mg/kg cadmium chloride or higher), testicular mice, rats, rodents includes interstitial edema, hemorrhage, changes the seminiferous tubules affecting spermatogenesis. Necrosis is evident by 48 h. goal of this study was to fine map identify cdm gene, gene that when mutated prevents cadmium-induced toxicity mouse strains with mutation gene. A serine-threonine phosphatase, calcineurin (CN), subunit A, isoform (Ppp3ca), one seven candidates region narrowed from 5.6 2.0 Mb on chromosome 3. An inhibitor CN, immunosuppressant, FK506, prevented five pathological categories, including vascular endothelial epithelial endpoints. Inductively coupled plasma-mass spectrometry revealed FK506 protected without lowering amount testes. Ppp3ca 2/2 mice were investigated but found exhibit endogenous abnormalities, making them an inappropriate model determining whether inactivation would afford protection toxicity. afforded current study, indicated CN likely be important mechanism testis possibly organs.