Roflumilast mitigates cisplatin-induced nephrotoxicity by regulating TNF-α/TNFR1/TNFR2/Fas/Caspase mediated apoptosis and inflammatory signals.

IF 2.8 4区医学 Q2 PHARMACOLOGY & PHARMACY Journal of Pharmacy and Pharmacology Pub Date : 2024-11-20 DOI:10.1093/jpp/rgae142

Priyal Patel, Sandip Patel, Yash Patel, Piyush Chudasama, Shailesh Soni, Samir Patel, Manan Raval

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Abstract

Purpose: The study aimed to evaluate the effect of roflumilast on modulating TNF-α/Caspase mediated cellular signals in cisplatin-induced nephrotoxicity in rats.

Methods: The rats (Male Wistar) were divided into five groups: normal control, disease control (cisplatin: 7 mg/kg i.p.), and cisplatin + roflumilast (0.25, 0.5, and 1 mg/kg b.w., p.o.). Cisplatin was administrated to rats on 0 day, and roflumilast treatment was started from the 6th-15th days. Blood and tissue were collected. Tissue was used to measure oxidative stress, such as malondialdehyde, superoxide dismutase, and catalase. Gene expression study involved real-time PCR of key genes linked with inflammation and apoptosis, i.e. Tnf-α, Tnfr1, Tnfr2, Fas, Nfkb, Casp3, Casp8, and Nrf2.

Findings: Cisplatin showed decreased serum creatinine and urea, high albumin, and total protein. Cisplatin elevated the malondialdehyde and reduced superoxide dismutase and catalase activity. Cisplatin also attributed an overexpression of Tnf-α, Tnfr1, Tnfr2, Nfkb, Fas, Casp3, and Casp8, and a decrease in the Nrf2 gene. Roflumilast decreased creatinine and urea and increased albumin and total protein levels. Roflumilast also downregulated the expression of Tnf-α, Tnfr1, Tnfr2, Nfkb, Fas, Casp3, and Casp8 and upregulated the Nrf2 gene expression.

Conclusion: Roflumilast manifested as a potential reno-protective agent against cisplatin-induced nephrotoxicity.

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罗氟司特通过调节TNF-α/TNFR1/TNFR2/Fas/Caspase介导的细胞凋亡和炎症信号，减轻顺铂诱导的肾毒性。

目的：本研究旨在评估罗氟司特在顺铂诱导的大鼠肾毒性中调节TNF-α/Caspase介导的细胞信号的作用：大鼠（雄性 Wistar）分为五组：正常对照组、疾病对照组（顺铂：7 mg/kg i.p.）、顺铂 + 罗氟司特（0.25、0.5 和 1 mg/kg b.w.，p.o.）。大鼠从第0天开始服用顺铂，第6-15天开始服用罗氟司特。收集血液和组织。组织用于测量氧化应激，如丙二醛、超氧化物歧化酶和过氧化氢酶。基因表达研究包括与炎症和细胞凋亡有关的关键基因的实时 PCR，即 Tnf-α、Tnfr1、Tnfr2、Fas、Nfkb、Casp3、Casp8 和 Nrf2：顺铂导致血清肌酐和尿素降低，白蛋白和总蛋白升高。顺铂升高了丙二醛，降低了超氧化物歧化酶和过氧化氢酶的活性。顺铂还会导致 Tnf-α、Tnfr1、Tnfr2、Nfkb、Fas、Casp3 和 Casp8 的过度表达，以及 Nrf2 基因的减少。罗氟司特能降低肌酐和尿素水平，提高白蛋白和总蛋白水平。罗氟司特还下调了Tnf-α、Tnfr1、Tnfr2、Nfkb、Fas、Casp3和Casp8的表达，并上调了Nrf2基因的表达：罗氟司特对顺铂诱导的肾毒性具有潜在的肾保护作用。

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来源期刊

Journal of Pharmacy and Pharmacology 医学-药学

CiteScore

6.60

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： JPP keeps pace with new research on how drug action may be optimized by new technologies, and attention is given to understanding and improving drug interactions in the body. At the same time, the journal maintains its established and well-respected core strengths in areas such as pharmaceutics and drug delivery, experimental and clinical pharmacology, biopharmaceutics and drug disposition, and drugs from natural sources. JPP publishes at least one special issue on a topical theme each year.