Hany H Arab1, Wafaa R Mohamed2, Bassant M Barakat3, El-Shaimaa A Arafa4. 1. Biochemistry Division and GTMR Unit, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Taif University, Taif 21974, Saudi Arabia; Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt. 2. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt. 3. Department of Pharmacology and Toxicology, Faculty of Pharmacy (Girls), Al Azhar University, Cairo, Egypt. 4. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt; Department of Pharmacology and Toxicology, College of Pharmacy and Health Sciences, Ajman University of Science and Technology, Ajman, United Arab Emirates. Electronic address: elshimaa.arafa@pharm.bsu.edu.eg.
Abstract
BACKGROUND: Despite the efficacy of cisplatin as a chemotherapeutic agent against various cancers, its clinical utility is limited by serious adverse reactions including nephrotoxicity. AIM: The current study aims to investigate the protective potential of tangeretin, a citrus flavone with marked antioxidant actions, against cisplatin-induced renal injury in rats. METHODS: Tangeretin was administered at 50 and 100 mg/kg p.o. for 1 week starting one day before cisplatin (7.5 mg/kg i.p.) injection. Likewise, silymarin was administered at 100 mg/kg orally. Renal function tests, histopathology, oxidative stress and inflammatory events were investigated. RESULTS: Tangeretin mitigated the increased levels of serum creatinine, blood urea nitrogen and histopathologic alterations evoked by cisplatin. It alleviated renal oxidative stress due to cisplatin by lowering lipid peroxides, nitric oxide and Nrf2 levels with concomitant enhancement of GSH and GPx. Tangeretin also suppressed the upregulated inflammatory response seen with cisplatin treatment by downregulation of activated NF-κB p65 protein expression together with its downstream effectors e.g., iNOS and TNF-α, with restoration of the anti-inflammatory interleukin IL-10. Additionally, it down-regulated the expression of caspase-3, an apoptotic marker, thus favoring renal cell survival. Importantly, tangeretin enhanced the cytotoxic actions of cisplatin in Hep3B and HCT-116 human cancer cell lines. CONCLUSION: Together, these findings accentuate the dual benefit of tangeretin: mitigation of renal injury-induced by cisplatin and enhancement of its cytotoxic effects.
BACKGROUND: Despite the efficacy of cisplatin as a chemotherapeutic agent against various cancers, its clinical utility is limited by serious adverse reactions including nephrotoxicity. AIM: The current study aims to investigate the protective potential of tangeretin, a citrus flavone with marked antioxidant actions, against cisplatin-induced renal injury in rats. METHODS:Tangeretin was administered at 50 and 100 mg/kg p.o. for 1 week starting one day before cisplatin (7.5 mg/kg i.p.) injection. Likewise, silymarin was administered at 100 mg/kg orally. Renal function tests, histopathology, oxidative stress and inflammatory events were investigated. RESULTS:Tangeretin mitigated the increased levels of serum creatinine, blood ureanitrogen and histopathologic alterations evoked by cisplatin. It alleviated renal oxidative stress due to cisplatin by lowering lipid peroxides, nitric oxide and Nrf2 levels with concomitant enhancement of GSH and GPx. Tangeretin also suppressed the upregulated inflammatory response seen with cisplatin treatment by downregulation of activated NF-κB p65 protein expression together with its downstream effectors e.g., iNOS and TNF-α, with restoration of the anti-inflammatory interleukin IL-10. Additionally, it down-regulated the expression of caspase-3, an apoptotic marker, thus favoring renal cell survival. Importantly, tangeretin enhanced the cytotoxic actions of cisplatin in Hep3B and HCT-116 humancancer cell lines. CONCLUSION: Together, these findings accentuate the dual benefit of tangeretin: mitigation of renal injury-induced by cisplatin and enhancement of its cytotoxic effects.
Authors: Marina Nery; Paula S Ferreira; Danielle R Gonçalves; Luis C Spolidorio; John A Manthey; Thais B Cesar Journal: Food Sci Nutr Date: 2021-02-12 Impact factor: 2.863
Authors: Félix Vargas; Paola Romecín; Ana I García-Guillén; Rosemary Wangesteen; Pablo Vargas-Tendero; M Dolores Paredes; Noemí M Atucha; Joaquín García-Estañ Journal: Front Physiol Date: 2018-04-24 Impact factor: 4.566