Preparation of gallic acid-loaded chitosan nanoparticles and their chemoprotective effects on N-ethyl-N-nitrosourea-induced hepatotoxicity and mortality in rats.

Autor: Shirmard LR; Department of Pharmaceutics, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran., Khezri S; Department of Pharmacology and Toxicology, Associate Professor of Toxicology and Pharmacology School of Pharmacy, Ardabil University of Medical Sciences, P.O. Box: 56189-53141, Ardabil, Iran., Ahadzadeh S; Students Research Committee, Faculty of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran., Azadimoghaddam P; Students Research Committee, Faculty of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran., Azizian S; Students Research Committee, Faculty of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran., Salimi A; Department of Pharmacology and Toxicology, Associate Professor of Toxicology and Pharmacology School of Pharmacy, Ardabil University of Medical Sciences, P.O. Box: 56189-53141, Ardabil, Iran. salimikd@yahoo.com.; Traditional Medicine and Hydrotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran. salimikd@yahoo.com.
Jazyk: angličtina
Zdroj: Journal of molecular histology [J Mol Histol] 2024 Nov 25; Vol. 56 (1), pp. 1. Date of Electronic Publication: 2024 Nov 25.
DOI: 10.1007/s10735-024-10280-8
Abstrakt: N-ethyl-N-nitrosourea (ENU) as n-nitrosamine and alkylating agent, ubiquitous within living cells and in the environment can act as a full carcinogen and induce tumor formation in various tissues such as liver. In this study, gallic acid-loaded chitosan nanoparticles (GANPs) were synthesized and evaluated for their chemopreventive effect against ENU-induced hepatotoxicity and mortality in rats. Twenty-four male Wistar rats were divided into four groups including: control, ENU (single doses of 50 mg/kg via intraperitoneal injection), GA + ENU and GANPs + ENU. Animals were orally pretreated with GA (50 mg/kg) and GANPs (50 mg/kg) for 30 days, and liver injuries induced by ENU on the 31st day of study. After ENU administration, weight changes and mortality were monitored during 30 days, and then the animals were sacrificed and alpha-fetoprotein (AFP) as a tumor marker, liver function tests (ALT, AST and ALP), oxidative stress markers (GSH and MDA), mitochondrial toxicity parameters, and histopathological assessment were evaluated. Except for AFP and MDA, ENU caused significant elevation of liver enzymes, mitochondrial ROS formation, collapse of mitochondrial membrane potential depletion of GSH, histopathological abnormalities and mortality in rats. Our data showed that GANPs significantly increased the survival of rats by up to 66%, delayed in death time and prevented weight changes after exposure to ENU. Moreover, GANPs restored liver enzyme levels, ROS formation, mitochondrial dysfunction, GSH levels, and histopathological abnormalities towards normal. Our findings suggest that GANPs revealed a significant protective effect against deadly toxicity induced by ENU as an alkylating full carcinogen agent in liver tissue.
Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: All experiments were performed based on standard protocols approved by the ethic committee of Ardabil University of Medical Sciences (ethic code: IR.ARUMS.AEC.1401.054). Consent to Participate: Not applicable. Consent to Publication: The Authors approve the publication of this study.
(© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)
Databáze: MEDLINE
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