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Updated: Aug 19, 2025
Acute Kidney Injury Model Induced by Cisplatin in Adult Zebrafish
Published on: May 15, 2021
Effect of SMTP-7 on Cisplatin-Induced Nephrotoxicity in Mice
Terumasa Hashimoto1,2, Keita Shibata1,3, Keiji Hasumi4
1Division of Pharmacology, Department of Pharmacology, Toxicology and Therapeutics, School of Pharmacy, Showa University.
Abstract:
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.
Insights
SMTP-7, a fungal metabolite, protects against cisplatin-induced acute kidney injury (AKI). It reduces kidney damage markers and inflammation, offering potential as a novel therapeutic for chemotherapy-induced AKI.
Area of Science:
- Nephrology
- Pharmacology
- Toxicology
Background:
- Acute kidney injury (AKI) is a serious side effect of cisplatin chemotherapy.
- Ischemia-reperfusion (IR) models show SMTP-7 has renoprotective properties.
- Cisplatin treatment leads to elevated blood urea nitrogen (BUN) and serum creatinine (Scr), indicating kidney damage.
Purpose of the Study:
- To investigate the efficacy of SMTP-7 in preventing or treating cisplatin-induced AKI.
- To evaluate the impact of SMTP-7 on kidney function markers and histological damage.
- To explore the underlying mechanisms, including the role of tumor necrosis factor-alpha (TNF-α).
Main Methods:
- Rats received intravenous cisplatin (20 mg/kg) to induce AKI.
- SMTP-7 was administered at varying doses and timings post-cisplatin.
- Kidney function was assessed by measuring BUN and Scr levels.
- Renal histology examined tubular necrosis, dilatation, and regeneration.
- TNF-α mRNA expression was analyzed.
Main Results:
- Cisplatin significantly increased BUN and Scr levels, with histological evidence of tubular injury.
- SMTP-7 dose-dependently inhibited the cisplatin-induced rise in BUN and Scr.
- The most effective treatment involved administering SMTP-7 24 hours after cisplatin.
- SMTP-7 (10 mg/kg) ameliorated tubular necrosis and dilatation.
- Cisplatin upregulated TNF-α mRNA; SMTP-7 administration attenuated this upregulation.
Conclusions:
- SMTP-7 demonstrates significant renoprotective effects against cisplatin-induced AKI.
- The protective mechanism involves the inhibition of pro-inflammatory cytokines, particularly TNF-α.
- SMTP-7 shows promise as a novel therapeutic agent for preventing or treating cisplatin-induced nephrotoxicity.
