Curcumin-loaded chitosan nanoparticles alleviate fenpropathrin-induced hepatotoxicity by regulating lipogenesis and pyroptosis in rats

Leena S Alqahtani; Yasmina M Abd-Elhakim; Amany Abdel-Rahman Mohamed; Norhan E Khalifa; Tarek Khamis; Badriyah S Alotaibi; Manal Alosaimi; Sanad S El-Kholy; Samah S Abuzahrah; Naira ElAshmouny; Areej Adeeb Eskandrani; Rasha A Gaber

doi:10.1016/j.fct.2023.114036

Curcumin-loaded chitosan nanoparticles alleviate fenpropathrin-induced hepatotoxicity by regulating lipogenesis and pyroptosis in rats

Food Chem Toxicol. 2023 Oct:180:114036. doi: 10.1016/j.fct.2023.114036. Epub 2023 Sep 14.

Affiliations

¹ Department of Biochemistry, College of Science, University of Jeddah, Jeddah, 23445, Saudi Arabia.
² Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
³ Department of Physiology, Faculty of Veterinary Medicine, Matrouh University, Matrouh, 51511, Egypt.
⁴ Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, 44511, Zagazig, Egypt; Laboratory of Biotechnology, Faculty of Veterinary Medicine, Zagazig University, 44519, Zagazig, Egypt.
⁵ Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia. Electronic address: bsalotaibi@pnu.edu.sa.
⁶ Department of Basic Medical Sciences, College of Medicine, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
⁷ Department of Physiology, Faculty of Medicine, Kafrelsheikh University, Kafrelsheikh, Egypt.
⁸ Department of Biological Sciences, College of Science, University of Jeddah, 21959, Saudi Arabia.
⁹ Histology and Cell biology, Faculty of Medicine, Kafr Elsheikh University, Egypt.
¹⁰ Chemistry Department, College of Science, Taibah University, Medina, 30002, Saudi Arabia.
¹¹ Medical Biochemistry Department, Faculty of Medicine, Tanta University, Egypt.

PMID: 37714448
DOI: 10.1016/j.fct.2023.114036

Abstract

In this study, the probable alleviative role of curcumin (CMN) (50 mg/kg b.wt) or curcumin-loaded chitosan nanoparticle (CLC-NP) (50 mg/kg b.wt) was assessed against the hepatotoxic effect of a widely used pyrethroid insecticide, fenpropathrin (FEN) (15 mg/kg b.wt) in rats in a 60-day experiment. The results revealed that CMN and CLC-NP significantly suppressed the FEN-induced increment in serum hepatic enzyme activities (ALT, AST, and ALP) and hyperbilirubinemia. Moreover, FEN-associated dyslipidemia, hepatic oxidative stress, and altered hepatic histology were significantly rescued by CMN and CLC-NP. Furthermore, the increased TNF-α and Caspase-3 immunoexpression in hepatic tissues of FEN-exposed rats was significantly reduced in CMN and CLC-NP-treated ones. FEN exposure significantly upregulated the pyroptosis-related genes, including GSDMD, Casp-1, Casp-3, Casp-8, IL-18, TNF-α, IL-1β, and NF-κB and altered the expression of lipogenesis-related genes including SREBP-1c, PPAR-α, MCP1, and FAS in the hepatic tissues. Nevertheless, the earlier disturbances in gene expression were corrected in CMN and CLC-NP-treated groups. Of note, compared to CMN, CLC-NP was more effective at inhibiting oxidative damage and controlling lipogenesis and pyroptosis in the hepatic tissues of FEN-exposed rats. Conclusively, the current study findings proved the superior and useful role of CLC-NP in combating pollutants associated with hepatic dysfunction.

Keywords: Chitosan nanoparticles; Inflammation; Lipogenesis; Liver; Pesticides; Pyroptosis.