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Germacrone Reduces Cisplatin-Induced Toxicity of Renal Proximal Tubular Cells via Inhibition of Organic Cation Transporter.
Soodvilai, Sirima; Meetam, Paranee; Siangjong, Lawan; Chokchaisiri, Ratchanaporn; Suksamrarn, Apichart; Soodvilai, Sunhapas.
Afiliação
  • Soodvilai S; Department of Pharmaceutical Technology, College of Pharmacy, Rangsit University.
  • Meetam P; Department of Biopharmacy, Faculty of Pharmacy, Silpakorn University.
  • Siangjong L; Department of Biopharmacy, Faculty of Pharmacy, Silpakorn University.
  • Chokchaisiri R; Department of Chemistry, School of Science, University of Phayao.
  • Suksamrarn A; Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University.
  • Soodvilai S; Research Center of Transporter Protein for Medical Innovation and Department of Physiology, Faculty of Science, Mahidol University.
Biol Pharm Bull ; 43(11): 1693-1698, 2020.
Article em En | MEDLINE | ID: mdl-33132314
Cisplatin is a widely used chemotherapy for solid tumors; however, its benefits are limited by serious nephrotoxicity, particularly in proximal tubular cells. The present study investigated the renoprotective effect and mechanisms of germacrone, a bioactive terpenoid compound found in Curcuma species on cisplatin-induced toxicity of renal cells. Germacrone (50 and 100 µM) attenuated apoptosis of human renal proximal tubular cells, RPTEC/TERT1 following treatment with 50 µM cisplatin and for 48 h. Co-treating RPTEC/TERT1 cells with cisplatin and germacrone significantly reduced cellular platinum content compared with cisplatin treatment alone. The effect of germacrone on organic cation transporter 2 (OCT2) which is a transporter responsible for cisplatin uptake was determined. Germacrone showed an inhibitory effect on OCT2-mediated methyl-4-phenylpyridinium acetate (3H-MPP+) uptake with IC50 of 15 µM with less effect on OCT1. The germacrone's protective effect on cisplatin-induced cytotoxicity was not observed in cancer cells; cisplatin's anti-cancer activity was preserved. In conclusion, germacrone prevents cisplatin-induced toxicity in renal proximal tubular cells via inhibition OCT2 transport function and reducing cisplatin accumulation. Thus germacrone may be a good candidate agent used for reducing cisplatin-induced nephrotoxicity.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cisplatino / Sesquiterpenos de Germacrano / Injúria Renal Aguda / Transportador 2 de Cátion Orgânico / Túbulos Renais Proximais Limite: Animals / Humans Idioma: En Revista: Biol Pharm Bull Assunto da revista: BIOQUIMICA / FARMACOLOGIA Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cisplatino / Sesquiterpenos de Germacrano / Injúria Renal Aguda / Transportador 2 de Cátion Orgânico / Túbulos Renais Proximais Limite: Animals / Humans Idioma: En Revista: Biol Pharm Bull Assunto da revista: BIOQUIMICA / FARMACOLOGIA Ano de publicação: 2020 Tipo de documento: Article