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Long-term exposure to p-Nitrophenol induces hepatotoxicity via accelerating apoptosis and glycogen accumulation in male Japanese quails

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Abstract

p-Nitrophenol (PNP) is the main end product of organophosphorus insecticides and a derivative of diesel exhaust particles. In addition to its unfavorable impact on reproductive functions in both genders, it also has various harmful physiological effects including lung cancer and allergic rhinitis. The identification of the cellular readout that functions in metabolic pathway perpetuation is still far from clear. This research aimed to study the impact of chronic PNP exposure on the health condition of the liver in Japanese quails. Quails were exposed to different concentrations of PNP as follows: 0.0 (control), 0.01mg (PNP/0.01), 0.1mg (PNP/0.1), and 1mg (PNP/1) per kg of body weight for 2.5 months through oral administration. Liver and plasma samples were collected at 1.5, 2, and 2.5 months post-treatment for biochemical, histopathology, and immunohistochemistry assessment. The plasma aspartate aminotransferase (AST) level was assessed enzymatically. The livers were collected for histopathology, glycogen accumulation, proliferating cell nuclear antigen (PCNA), and apoptosis assessment. Our results revealed an irregularity in body weight due to the long-term exposure of PNP with a significant reduction in liver weight. PNP treatment caused histopathological alterations in the hepatic tissues which increased in severity by the long-term exposure. The low dose led to mild degeneration with lymphocytic infiltration, while the moderate dose has a congestion effect with some necrosis; meanwhile severe hepatocyte degeneration and RBCs hemolysis were noticed due to high dose of PNP. Glycogen accumulation increased in hepatocytes by prolonged exposure to p-Nitrophenol with the highest intensity in the group treated by the high dose. Moderate and high doses of PNP resulted in a significant increase in apoptosis and hepatocytes’ proliferation at the different time points after treatment. This increase is markedly notable and maximized at 2.5 months post-treatment. The damage occurred in a time-dependent manner. These changes reflected on the plasma hepatic enzyme AST that was clearly increased at 2.5 months of exposure. Therefore, it could be concluded that PNP has profound toxic effects on the liver in cellular level. Taking into consideration the time and dose factors, both have a synergistic effect on the accumulation of glycogen, apoptosis, and cellular proliferation, highlighting the power of cellular investigation which will potentially open the door for earlier medical intervention to counteract this toxicity. Collectively, PNP could have critical hurtful effects on the health of human beings, wild animals as well as livestock.

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Acknowledgements

The authors gratefully acknowledge the help of Dr. Gen Watanabe, professor and head of Physiology Department of Veterinary Medicine, Tokyo University of Agriculture and Technology, for providing us with the PNP.

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, 41522, Egypt

    Eman A. Ahmed

  2. Proteomics and Metabolomics Unit, Department of Basic Research, Children’s Cancer Hospital Egypt 57357, Cairo, 11441, Egypt

    Eman A. Ahmed

  3. Zoology Department, Faculty of Sciences, Suez University, Suez, Egypt

    Howayda E. Khaled

  4. Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, 41522, Egypt

    Ahmed K. Elsayed

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  1. Eman A. Ahmed
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  2. Howayda E. Khaled
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Contributions

E.A. Ahmed contribute to the design and implementation of the research, data analysis, and manuscript revision, H.E. Khaled contributed to writing and manuscript revision, and A.K. Elsayed contributed to discussion of the results, data analysis, and writing and revision of the manuscript.

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Correspondence to Eman A. Ahmed.

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These birds were treated humanely following the established guidelines and principles of Faculty of Veterinary medicine, Suez Canal University, Egypt, which are approved by the ethics committee for using laboratory animals’ experiments.

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Ahmed, E.A., Khaled, H.E. & Elsayed, A.K. Long-term exposure to p-Nitrophenol induces hepatotoxicity via accelerating apoptosis and glycogen accumulation in male Japanese quails. Environ Sci Pollut Res 28, 44420–44431 (2021). https://doi.org/10.1007/s11356-021-13806-9

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