Details

Autor(en) / Beteiligte

• Hashimoto, Terumasa
• Shibata, Keita
• Hasumi, Keiji
• Honda, Kazuo
• Nobe, Koji

Titel

Effect of SMTP-7 on Cisplatin-Induced Nephrotoxicity in Mice

Ist Teil von

• Biological and Pharmaceutical Bulletin, 2022/12/01, Vol.45(12), pp.1832-1838

Ort / Verlag

Tokyo: The Pharmaceutical Society of Japan

Erscheinungsjahr

2022

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• SMTP-7, a fungal metabolite, is reported to have a high degree of availability for the ischemia–reperfusion (IR)-induced acute kidney injury (AKI) model. Cisplatin, a widely used anticancer drug, has serious side effects, such as AKI. Hence, we aimed to examine the effect of SMTP-7 on cisplatin-induced AKI in this study. Significant increases in blood urea nitrogen (BUN) and serum creatinine (Scr) were observed at 72 h after the intravenous infusion of cisplatin (20 mg/kg). Histologically, necrosis and dilatation (hyaline casts) as well as regeneration were observed in proximal tubules. SMTP-7 inhibited the elevation on BUN and Scr caused by cisplatin dose dependently. The efficacy of SMTP-7 was notable when the drug was administered on the day after cisplatin treatment, whereas the repeated administration of the drug did not result in an enhanced efficacy. Moreover, 10 mg/kg of SMTP-7 considerably ameliorated tubular necrosis and dilatation. The cisplatin treatment also caused an up-regulation of tumor necrosis factor-α (TNF-α) mRNA expression prior to the elevation of the levels of BUN and Scr. Administration of SMTP-7 (10 mg/kg) at 24 h after the cisplatin infusion alleviated the up-regulation of TNF-α mRNA expression. These findings suggest that SMTP-7 exhibits a renoprotective effect against cisplatin infusion based on the inhibition of the expression of pro-inflammatory cytokines such as TNF-α and may be expected a new effective drug for the treatment of cisplatin-induced AKI.