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Chem Biol Interact. 2019 May 16;308:137-146. doi: 10.1016/j.cbi.2019.05.029. [Epub ahead of print]

Wogonin pre-treatment attenuates cisplatin-induced nephrotoxicity in rats: Impact on PPAR-γ, inflammation, apoptosis and Wnt/β-catenin pathway.

Author information

1
Department of Pharmacology, The National Organization for Drug Control and Research, Cairo, Egypt.
2
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt. Electronic address: reemelnaga@pharma.asu.edu.eg.
3
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.

Abstract

Cisplatin, a platinum chemotherapeutic agent, is used in a diversity of malignancies; nevertheless, the excessive nephrotoxicity following cisplatin treatment is the dose-limiting devastating reaction. This study was designed to explore the possible nephroprotective impact of wogonin, a forceful anti-oxidant, anti-inflammatory, and anti-tumor agent, in a rat model of cisplatin-induced renal injury. The potential nephroprotective mechanisms were additionally investigated. Wogonin was given at a dose of 40 mg/kg. Acute nephrotoxicity was indicated by a significant rise in BUN, and serum creatinine levels in cisplatin-injected rats. Also, cisplatin enhanced the lipid peroxidation, diminished GSH, catalase, and PPAR-γ levels. Additionally, cisplatin-injected rats showed a significant rise in tissue levels of IL-1β, TNF-α, NF-kB, and caspase-3 enzymatic activity. Notably, the pre-treatment with wogonin ameliorated the nephrotoxicity indices, oxidative stress, inflammation, and apoptosis induced by cisplatin. Also, wogonin up-regulated PPAR-γ expression. The involvement of Wnt/β-catenin pathway was debatable; however, our findings showed that it was significantly induced by cisplatin. Wogonin pre-treatment markedly attenuated Wnt/β-catenin pathway. Collectively, these findings imply that wogonin is a promising nephroprotective agent that improves the therapeutic index of cisplatin via reducing oxidative stress, inflammation as well as inducing PPAR-γ. Also, Wnt/β-catenin pathway is partially involved in the pathogenesis of cisplatin nephrotoxicity.

KEYWORDS:

Cisplatin; Nephrotoxicity; PPAR-γ; Wnt/β-catenin pathway; Wogonin

PMID:
31103702
DOI:
10.1016/j.cbi.2019.05.029

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