Wogonin pre-treatment attenuates cisplatin-induced nephrotoxicity in rats: Impact on PPAR-γ, inflammation, apoptosis and Wnt/β-catenin pathway
| Autor: | Mariane G. Tadros, Hala M. Fawzy, Alaa M. Badawy, Amany M. Gad, Reem N. El-Naga |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Interleukin-1beta Apoptosis Pharmacology Kidney Protective Agents Toxicology medicine.disease_cause Nephrotoxicity Rats Sprague-Dawley Lipid peroxidation 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Wogonin medicine Animals Wnt Signaling Pathway Inflammation Cisplatin Tumor Necrosis Factor-alpha Wnt signaling pathway General Medicine Acute Kidney Injury Glutathione Rats Up-Regulation PPAR gamma 030104 developmental biology chemistry 030220 oncology & carcinogenesis Nephroprotective Agent Flavanones Oxidative stress medicine.drug |
| Zdroj: | Chemico-Biological Interactions. 308:137-146 |
| ISSN: | 0009-2797 |
| DOI: | 10.1016/j.cbi.2019.05.029 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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