RESUMO
Silk fibroin (SF) is a natural polymeric biomaterial widely used in the preparation of drug delivery systems. Herein, silk fibroin peptide (SFP) was self-assembled into nanofibers, encapsulated a poorly water-soluble drug baicalein (SFP/BA NFs), and then used to protect against cisplatin-induced acute kidney injury (AKI). Specifically, the SFP/BA NFs significantly enhanced the aqueous dispersity, storage stability, and in vitro antioxidant activity of BA. SFP/BA NFs increased the drug uptake and localization to mitochondria. In vitro results demonstrated that SFP/BA NFs can relieve the cisplatin-induced HK-2 cell damage, and inhibit the cisplatin-induced accumulation of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) disruption. Mechanism studies demonstrated that SFP/BA NFs may exert nephroprotective effects by inhibiting both the cisplatin-induced DNA damage and the cGAS/STING pathway activation. In vivo results showed that cisplatin treatment resulted in decreased body weight, increased serum creatinine (SCr), and increased blood urea nitrogen (BUN) levels, while SFP/BA NFs reversed the above symptoms. Furthermore, SFP/BA NFs reversed the cisplatin-induced abnormal changes of antioxidant enzymes (e.g., SOD and GSH), and inhibited the cisplatin-induced DNA damage as well as the activation of cGAS/TING. Above all, our results revealed the potential of SFP/BA NFs to protect against cisplatin-induced AKI.
Assuntos
Injúria Renal Aguda , Fibroínas , Nanofibras , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/prevenção & controle , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Apoptose , Materiais Biocompatíveis/uso terapêutico , Cisplatino/farmacologia , Creatinina , Fibroínas/química , Flavanonas , Humanos , Rim/metabolismo , Nanofibras/química , Nucleotidiltransferases/farmacologia , Nucleotidiltransferases/uso terapêutico , Peptídeos/química , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase , Tolnaftato/efeitos adversos , Água/farmacologiaRESUMO
Teratogenic studies of tolnaftate, an antifungal agent, in humans have not been published. The population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996 contained 22843 fetuses or newborns with congenital abnormalities and 38151 matched controls without congenital abnormalities. The mothers of 13 cases and 13 controls were treated with tolnaftate spray during pregnancy. Four cases had congenital cardiovascular malformations in the group of cases (OR with 95% CI: 3.1, 1.0-9.7), but these cardiac defects were different. Thus, it is a signal for the potential teratogenic risk of tolnaftate in a case-control study, though the number of cases and controls were limited. Therefore, international collaboration is needed for the final conclusion.
Assuntos
Anormalidades Induzidas por Medicamentos/epidemiologia , Antifúngicos/efeitos adversos , Teratógenos , Tolnaftato/efeitos adversos , Administração Tópica , Adulto , Aerossóis , Antifúngicos/administração & dosagem , Feminino , Humanos , Hungria/epidemiologia , Gravidez , Vigilância de Produtos Comercializados , Tolnaftato/administração & dosagemRESUMO
In a double-blind trial clotrimazole cream was compared with tolnaftate cream in the treatment of dermatophytoses and with nystatin cream in the treatment of candidoses. Clotrimazole was shown to be effective against both dermatophytoses and candidoses and was as effective and acceptable as tolnaftate and nystatin creams in each condition.
