Key result
Pomegranate-nanoparticles ameliorated cisplatin-induced nephrotoxicity by attenuating oxidative stress and inflammation, without compromising cisplatin's antitumor efficacy in mice.
Why the study?
Cisplatin is limited by nephrotoxicity, while pomegranate is a protective antioxidant whose therapeutic application is hindered by reduced solubility and low bioavailability.
Does the addition of Pomegranate-Nanoparticles (PE-NPs) to cisplatin prevent nephrotoxicity and maintain anti-cancer efficacy in a mice model of Ehrlich solid carcinoma?
Does the addition of Pomegranate-Nanoparticles (PE-NPs) to cisplatin prevent nephrotoxicity and maintain anti-cancer efficacy in a mice model of Ehrlich solid carcinoma?
Pomegranate-nanoparticles may serve as a potent adjunct to cisplatin therapy to prevent nephrotoxicity without compromising anticancer efficacy in preclinical models.
May protect against cisplatin nephrotoxicity in mice without compromising efficacy; hypothesis-generating for clinical translation.
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.
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Harakeh et al. (2022) studied Ehrlich solid carcinoma and Cisplatin-induced nephrotoxicity. Pomegranate-Nanoparticles (PE-NPs) vs. Cisplatin alone, tumor alone, and control was evaluated on Cisplatin-induced nephrotoxicity (oxidative stress, lipid peroxidation, and inflammation). Pomegranate-nanoparticles ameliorated cisplatin-induced nephrotoxicity by attenuating oxidative stress and inflammation, without compromising cisplatin's antitumor efficacy in mice.
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