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This study was designed to explore the hepatotoxicity of emamectin in male rats and the possible effect of Nigella sativa oil (NSO) in ameliorating this. Twenty-eight male rats were used in this study. They were divided into four groups, Control group: rats orally administered distilled water; NSO group: rats administered NSO orally; EMB group: rats administered emamectin benzoate orally; and EMB+NSO group: rats orally co-administered NSO with EMB, with the administrations being performed every other day for 6 weeks. Body weight was measured, liver alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) activities were determined, and total protein and albumin levels were recorded. Histopathological examination of the liver was also performed, along with caspase-3 and TNF-α immunostaining of liver tissue. EMB treatment resulted in decreased body weight, while the co-administration of NSO modulated the EMB-induced alterations in body weight. There were also increases in the activities of serum ALT, AST, and ALP and decreases in total protein and albumin levels in the EMB group. Co-treatment with NSO significantly reduced serum ALT, AST, and ALP and improved total protein and albumin levels. Histopathological examination of the liver in the EMB group revealed the presence of different histopathological alterations that were improved by the co-administration of NSO. Immunostaining of caspase-3 and TNF-α in the liver revealed strong expression in the EMB-treated group. Meanwhile, the EMB+NSO group showed weak positivity for immunoreactive cells.

Badr E El Bialy, 1 Ragaa A Hamouda, 2, 3 Mabrouk A Abd Eldaim, 4 Salah S El Ballal, 5 Hanim S Heikal, 6 Hanem K Khalifa, 7 Wael N Hozzein 8, 9 1Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, University of Sadat City, Sadat City, Egypt; 2Department of Biology, Faculty of Sciences and Arts-Khulais, University of Jeddah, Jeddah, Saudi Arabia; 3Department of Microbial Biotechnology, Genetic Engineering & Research Institute, University of Sadat City, Sadat City, Egypt; 4Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, Menoufia University, Sheben Elkom 32511, Egypt; 5Department of Pathology, Faculty of Veterinary Medicine, University of Sadat City, Sadat City, Egypt; 6Department of Animal Husbandry and Animal Wealth Development, Faculty of Veterinary Medicine, University of Sadat City, Sadat City, Egypt; 7Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, University of Sadat City, Sadat City, Egypt; 8Bioproducts Research Chair, Zoology Department, College of Science, King Saud University, Riyadh, Saudi Arabia; 9Botany and Microbiology Department, Faculty of Science, Beni-Suef University, Beni-Suef, EgyptCorrespondence: Mabrouk A Abd EldaimDepartment of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, Menoufia University, Sheben Elkom 32511, EgyptTel/ Fax +20482193756; +201117484718Email mabroukattia@vet.menofia.edu.egWael N HozzeinBioproducts Research Chair, Zoology Department, College of Science, King Saud University, Sheben Riyadh, Saudi ArabiaEmail whozzein@ksu.edu.saIntroduction: Copper oxide nanoparticles (CuO-NPs) are widely used as feed additives for livestock and poultry and implicated in many biomedical applications; however, overload of copper NPs induces various toxicological changes and dysfunction of animal’s organs. Thus, this study was designed to evaluate the comparative toxicological effects of biologically and chemically synthesized CuO-NPs on mice.Methods: Transmission electron microscopy (TEM), X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FT-IR) were used to characterize the sizes, shapes and functional groups of CuO-NPs. Forty-five mice were randomly allocated into three groups. Control group received distilled water. The second group was administered a single dose of biologically synthesized CuO-NPs (500 mg/kg bw) orally. The third group was administered a single dose of chemically synthesized CuO-NPs (500 mg/kg bw) orally.Results: TEM revealed that biologically synthesized NPs were spherical in shape, whereas chemically synthesized NPs were spherical or elongated in shape. XRD showed that the size of biologically synthesized NPs ranged from 4.14 to 12.82 nm and that of chemically synthesized NPs ranged from 4.06 to 26.82 nm. FT-IR spectroscopy indicated that the peaks appeared between 779 cm− 1 and 425 cm− 1 in biologically synthesized NPs and between 858 cm− 1 and 524 cm− 1 in chemically synthesized NPs were for Cu-O nanostructure. Four mice died due to administration of biologically synthesized CuO-NPs. Both biologically and chemically synthesized CuO-NPs induced leukocytosis, elevated serum activities of alanine aminotransferase and aspartate aminotransferase and serum levels of urea and creatinine and increased P53 mRNA and caspase-3 protein expressions in hepatic tissues. Moreover, CuO-NPs induced degenerative and necrotized changes in hepatic, renal and splenic tissues. Biochemical, apoptotic and pathological changes were more serious in mice administered with biologically synthesized CuO-NPs.Conclusion: This study indicated that a high dose of biologically and chemically synthesized CuO-NPs induced adverse effects on hepatic, renal and splenic tissues. At the same dose level, the biologically synthesized CuO-NPs evoked more potent toxic effects than the chemically synthesized CuO-NPs.Keywords: biologically synthesized CuO-NPs, chemically synthesized CuO-NPs, P53, caspase