Journal of Animal Health and Production

Research Article
J. Anim. Health Prod. 9(s1): 110-120
Http://dx.doi.org/10.17582/journal.jahp/2020/9.s1.110.120
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Safaa I. Khater1, Rasha M. M. Ezz-eldin1,2, Saydat Saad1, Fatma Gamal1, El-Ayadi D. El-Abed3, Ahmed Hamed Arisha4,5*

1Department of Biochemistry, Faculty of Veterinary Medicine, Zagazig University, 44519 Zagazig, Egypt; 2Central Laboratory, Veterinary Hospital, Faculty of Veterinary Medicine, Zagazig University, 44519 Zagazig, Egypt; 3Faculty of Public Health, Sabratha University, Sabratha, Libya; 4Department of Animal Physiology and Biochemistry, Faculty of Veterinary Medicine, Badr University in Cairo (BUC), Badr City, Cairo, Egypt. 5Department of Physiology, Faculty of Veterinary Medicine, Zagazig University, 44519 Zagazig, Egypt

Abstract | Drug delivery systems including nanoparticles are used to enhance anticancer drugs therapeutic and pharmacological properties. A biodegradable polymer chitosan (CS) was used in this study for Doxorubicin (DOX) delivery. In Ehrlich ascites carcinoma (EAC) tumor, anticancer activity of these nanoparticles was investigated in-vivo. EAC bearing mice treated with free DOX revealed significantly increase in the levels of blood urea nitrogen (BUN) and creatinine compared with EAC bearing mice group. At the same time, the levels of BUN, creatinine and TNF-α in EAC bearing mice treated with doxorubicin capsulated chitosan nanoparticles (DOX-CNs) at dose (1-3 mg/kg) revealed significant declines when compared with EAC bearing mice treated with free DOX. The expression levels of miR-34a was found to be significantly up-regulated in DOX-treated mice accompanied by non-significantly change in the mRNA expression of renal Sirt1 compared with EAC- bearing mice group. The levels of miR-122 were non-significantly changed in renal tissue of EAC bearing mice given free DOX accompanied by significantly up-regulation in the expression levels of renal FOXO3 gene compared to EAC bearing mice and negative control groups. On the other hand, these levels were reversed in DOX capsulated chitosan nanoparticles treatment at dose (1mg/kg) but not at dose (2 or 3 mg/kg). The study reported the safety of administering DOX capsulated chitosan nanoparticles at dose
(1mg/kg) and elicited anti-carcinogenic activity as compared with DOX itself.

Keywords | Ehrlich Ascites Carcinoma; Doxorubicin; Chitosan nanoparticles; Nephrotoxicity; miR 34-a; miR-122; FOXO3, Sirt1