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

Steve Harakeh,Torki Alzughaibi,Isaac O Akefe,Saber H Saber,Mohammed S Almuhayawi,Shaker Mousa,Soad K Al Jaouni,Yousef Almehmadi,Dhruba J Bharali,Soad Shaker Ali

doi:10.3390/molecules27051605

Abstract

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.

Highlights

The global population-based disease incidence data has reported a geometric rise in the occurrence of cancer, ranking among the leading causes of mortality and giving the global rise in risk factors especially in developing economies, it is expected to reach28.4 million cases in 2040 [1]
The size distribution and zeta potential of PE-NPs in aqueous diffusion was identified via Electrophoretic Light Scattering (ELS) and Dynamic Light Scattering (DLS) methods as previously described in our previous publication on the testing of the same compound in a different biological system [26,27]
Our result demonstrated that PE-NPs were efficient in preventing CISP-induced nephrotoxicity in Ehrlich solid carcinoma (ESC) mice

Summary

Introduction

The global population-based disease incidence data has reported a geometric rise in the occurrence of cancer, ranking among the leading causes of mortality and giving the global rise in risk factors especially in developing economies, it is expected to reach28.4 million cases in 2040 [1]. Projections by the American Cancer Society estimates the numbers of new cancer cases be reach about 1,918,030 in 2022 [2]. Several ongoing studies investigating the use of different chemotherapeutic agents on several drug targets critical for the prevention and control of cancer. Owing to its DNA binding affinity and ability to induce the destruction of cytotoxic DNA, Cisplatin (CISP) remains a potent chemotherapeutic agent widely administered in the management of solid tumors [3]. Alongside impairing the innate cellular ability to induce apoptosis and repair [4], it causes nephrotoxicity [5], myelosuppression, vomiting and nausea among other notable undesirable adverse effects [6]. Owing to its effect on the proximal tubule in rodents, nephrotoxicity has been implicated as the major side effect related to CISP administration [7,8]. The mechanism of action by which CISP induces nephrotoxicity remain unclear

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