Novel Pomegranate-Nanoparticles Ameliorate Cisplatin-Induced Nephrotoxicity and Improves Cisplatin Anti-Cancer Efficacy in Ehrlich Carcinoma Mice Model

Molecules

Soad Shaker Ali¹  Mohammed S. Almuhayawi²  Isaac O. Akefe³  Torki Alzughaibi⁴  Steve Harakeh⁴  Saber H. Saber⁵  Yousef Almehmadi⁶  Shaker Mousa⁷  Dhruba J. Bharali⁷  Soad K. Al Jaouni⁸ 

[1] Department of Anatomy, Faculty of Medicine, King Abdulaziz University, Jeddah 22230, Saudi Arabia;Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah 22230, Saudi Arabia;Department of Physiology, Biochemistry and Pharmacology, Faculty of Veterinary Medicine, University of Jos, Jos 930003, Nigeria;King Fahd Medical Research Center, King Abdulaziz University, Jeddah 22230, Saudi Arabia;Laboratory of Molecular Cell Biology, Department of Zoology, Faculty of Science, Assiut University, Assiut 71515, Egypt;Rabigh Faculty of Medicine, King Abdulaziz University, Jeddah 22230, Saudi Arabia;The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA;Yousef Abdul Latif Jameel Scientific Chair of Prophetic Medicine Application, Faculty of Medicine, King Abdulaziz University, Jeddah 22230, Saudi Arabia;

关键词: cisplatin;    antioxidant;    pomegranate;    nephrotoxicity;    nano-formulation;   

DOI  :  10.3390/molecules27051605

来源: DOAJ

【 摘 要 】

Cisplatin (CISP) is one of the most widely used anti-cancer chemotherapeutic agents with remarkable efficacy against various types of cancers. However, it has been associated with nephrotoxicity amongst other undesirable side effects. Pomegranate (PE) is a potent antioxidant and anti-inflammatory agent effective against cancer, with a superior benefit of not being associated with the common toxicities related to the use of conventional chemotherapeutic agents. However, the application of PE is limited by its reduced solubility and decreased bioavailability. We investigated the potential of a novel nanoparticle (NP) enclosing PE to enhance its solubility and improve its bioavailability, and efficacy to prevent CISP-associated nephrotoxicity in a mice model of Ehrlich solid carcinoma (ESC). All mice were grouped into four cohorts: (I) control, (II) tumor, (III) CISP, and (IV) CISP + PE-NPs. The data obtained demonstrated that PE-NPs was beneficial in potently ameliorating CISP-induced nephrotoxicity in ESC mice. PE-NPs significantly attenuated CISP-induced oxidative stress and lipid peroxidation in the kidney via improving activities of antioxidants (SOD, GSH, and CAT). Additionally, PE-NPs considerably decreased CISP-induced inflammation in the kidney by decreasing the levels of NF-kB, IL-1β, and TNF-α. Notably, PE-NPs did not assuage the antitumor efficacy of CISP as revealed by histological assessment and tumor weight data. In summary, PE-NPs may be a potent alternative anticancer therapy devoid of nephrotoxicity.

【 授权许可】

Unknown