ArticlePloS one2022
Hesperetin mitigates sorafenib-induced cardiotoxicity in mice through inhibition of the TLR4/NLRP3 signaling pathway.
Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 34 citations in OpenAlex.
- Cardioprotective role of vincamine in cyclophosphamide-induced cardiotoxicity through modulation of AMPK/SIRT1, PI3K/Akt, and MAPK pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Febuxostat attenuates chronic kidney disease induced by adenine in rats: role of TLR4/NF-κB/NLRP3/Caspase1/IL-1β pathway.Inflammopharmacology · 2026Article
- The hepatoprotective role of piperazine ferulate against cisplatin-induced hepatotoxicity in rats: insights into the Keap1/Nrf-2/HO-1 signaling and inflammatory pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- The advantages and challenges of sorafenib combination therapy: Drug resistance, toxicity and future directions (Review).Oncology letters · 2025Review
- Hesperetin Alleviates Bleomycin-Induced Pulmonary Fibrosis by Modulating Cellular Senescence and Promoting Impaired Autophagy in a CISD2-Dependent Manner.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Vitamin B17 alleviates Sorafenib-induced cardiotoxicity in Ehrlich Ascites Carcinoma mice via modulation of inflammatory and fibrotic pathways.Scientific reports · 2025Article
- Cilostazol alleviates imatinib-induced myocardial injury in rats by modulating the TGF-β1/MAPK, SHC/Grb2/SOS signaling pathways and upregulating miRNA-195-5P.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- The Imaging Value ofMolecular imaging and biology · 2025Article
- Understanding the Mechanisms of Chemotherapy-Related Cardiotoxicity Employing hiPSC-Derived Cardiomyocyte Models for Drug Screening and the Identification of Genetic and Epigenetic Variants.International journal of molecular sciences · 2025Review
- Natural Products From Traditional Chinese Medicine: Potential Therapeutic Agents in Cancer Therapy-Induced Cardiotoxicity.Drug design, development and therapy · 2025Review
- Preparation and characterization of Sorafenib nano-emulsion: impact on pharmacokinetics and toxicity; an in vitro and in vivo study.Drug delivery and translational research · 2024Article
- Prospects of compounds of herbal plants as anticancer agents: a comprehensive review from molecular pathways.Frontiers in pharmacology · 2024Review
- Understanding Sorafenib-Induced Cardiovascular Toxicity: Mechanisms and Treatment Implications.Drug design, development and therapy · 2024Review
- Ferroptosis inhibitor alleviates sorafenib-induced cardiotoxicity by attenuating KLF11-mediated FSP1-dependent ferroptosis.International journal of biological sciences · 2024Article
- Antioxidant, Antiapoptotic, and Anti-Inflammatory Effects of Hesperetin in a Mouse Model of Lipopolysaccharide-Induced Acute Kidney Injury.Molecules (Basel, Switzerland) · 2023Article
- Article
- [Hesperetin alleviates doxorubicin-induced cardiotoxicity by regulating the AMPK/NLRP3 pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical UniversityArticle
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sorafenib is an oral multi-kinase receptor inhibitor that targets various signaling pathways. It is used as the first line of treatment in advanced hepatocellular and renal cell carcinomas. Sorafenib was reported to induce cardiotoxicity due to myocyte necrosis. Hesperetin is a naturally occurring flavonoid with antioxidant and anti-inflammatory capabilities. This study investigated the putative protective effect of hesperetin against sorafenib-induced cardiotoxicity in mice through downregulation of NLRP3/TLR4 signaling and inhibition of apoptosis. Twenty-four male Swiss mice were distributed into four groups: untreated control, hesperetin (50 mg/kg/day, orally), sorafenib (100 mg/kg/day, orally), and combination (Hesperetin+Sorafenib). After a three-week treatment period, various biochemical parameters in cardiac tissues were assessed. TNF-α, IL-1β, and IL-6 levels were measured. Moreover, TLR4 and NLRP3 expressions were evaluated using Western blot analysis. Histopathological examination and immunohistochemical assessment of apoptotic activity were done. Compared with the sorafenib group, the combination group exhibited reduced TNF-α, IL-1β, IL-6 levels and lower NLRP3/TLR4 expressions. Histologically, the combination group showed improved myocardial histology and a marked decrease in collagen deposition. Immunohistochemical examination showed decreased caspase-3 and increased Bcl-2 expression. Before recommending hesperetin as an adjuvant, clinical studies are warranted for mitigating sorafenib cardiotoxicity.
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