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Ameliorative effect of N-acetylcysteine against glyphosate-induced hepatotoxicity in adult male albino rats: histopathological, biochemical, and molecular studies

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Abstract

Glyphosate (GLP) is the most commonly used herbicide that presents many hazards to the environment and living organisms. The present study aimed to explore hepatotoxic properties of GLP on adult albino rats, and the ability of N-acetylcysteine (NAC) to ameliorate these toxic effects. Thirty mature male albino rats were distributed into 3 groups (10 rats/group): Group I (C) a negative control, Group II (GLP) orally administered Roundup 0.8503 ml/kg/day which contain GLP (375 mg/kg) (1/10 of LD50) by gavage needle, and Group III (NAC+ GLP) received NAC (160 mg/kg, 1h before Roundup) by gavage needle and Roundup (0.8503 ml/kg) orally for 6 weeks. Blood and liver samples were collected and processed for biochemical, histopathological, ultrastructural, and immunohistochemical investigations. Group II displayed a significant elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) levels, as well as overexpression of apoptotic markers. The total antioxidant capacity “TAC” and mRNA expression of NRF2 were significantly decreased. Concerning the histopathological findings, there were various degenerative changes as the hepatocytes showed hydropic swelling with nuclear pyknosis. These alterations were confirmed ultrastructurally as most of the cytoplasmic organelles were lost and the mitochondria appeared to deteriorate. Immunohistochemical results showed intense immunoreactivity against proliferating cell nuclear antigen (PCNA) and caspase-3. NAC administration before GLP partially ameliorates these alterations. ALT, AST, and MDA levels as well as expression of apoptotic markers were significantly reduced. TAC and mRNA expression of NRF2 were significantly increased. Histopathological alterations were partially improved as the hepatocytes returned normal and ultrastructurally they showed nearly normal cytoplasmic organelles. Additionally, the intense expression of PCNA and caspase-3 was significantly reduced. We concluded that NAC can ameliorate most of the adverse effects of GLP exposure through its antioxidant property and free radicals scavenging capacity.

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Authors and Affiliations

  1. Cytology and Histology Department, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt

    Asmaa R. Hashim, Dina W. Bashir, Noha A. E. Yasin & El-Gharbawy S. M.

  2. Biochemistry and Chemistry of Nutrition Department, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt

    Mona K. Galal

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  1. Asmaa R. Hashim
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  2. Dina W. Bashir
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Contributions

Prof. El-Gharbawy S. M. conceived the study and designed the experimental protocol.

Asmaa R. Hashim, Dina W. Bashir, and Noha A. E. Yasin carried out the histopathological analysis and drafted the manuscript.

Mona K. Galal carried out the biochemical analysis.

All authors read, revised, and approved the final manuscript.

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Correspondence to Dina W. Bashir.

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All animals have been humanely cared for following the protocol accepted by the Institutional Animal Care and Use Committee (IACUC) of the Faculty of Veterinary Medicine, Cairo University (protocol no. Vet CU 160720196).

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Hashim, A.R., Bashir, D.W., Yasin, N.A.E. et al. Ameliorative effect of N-acetylcysteine against glyphosate-induced hepatotoxicity in adult male albino rats: histopathological, biochemical, and molecular studies. Environ Sci Pollut Res 28, 42275–42289 (2021). https://doi.org/10.1007/s11356-021-13659-2

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