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Impact of the nitric oxide substrate l-arginine alone and combined with atropine on malathion neuro and hepato-toxicity

  • Amany A. Sleem , Eman R. Youness EMAIL logo , Nermeen Shaffie , Heba A. Farid and Omar M. E. Abdel-Salam
Published/Copyright: October 28, 2025
Journal of Complementary and Integrative Medicine
From the journal Journal of Complementary and Integrative Medicine

Abstract

Objectives

We investigated the impact of the nitric oxide substrate l-arginine on the neuro- and hepato-toxic effects of malathion in rats.

Methods

Rats were treated intraperitoneally with malathion (150 mg/kg) alone or combined with l-arginine (100, 200 or 400 mg/kg), atropine (2 mg/kg) or l-arginine (200 mg/kg) combined with atropine (2 mg/kg). Rats were euthanized 4 h later, and their brains and livers analyzed for malondialdehyde, nitric oxide (NO), reduced glutathione (GSH), paraoxonase-1 (PON-1). Moreover, butyrylcholinesterase (BChE), interleukin-15 (IL-15) and anti-apoptotic protein B cell/lymphoma-2 (Bcl-2) were determined in brain tissue. Histopatholoy was also performed.

Results

Malathion significantly raised brain NO and malondialdehyde alongside with a notable drop in PON-1 activity and GSH levels relative to the saline control. Brain BChE and Bcl-2 were markedly inhibited whereas IL-15 significantly increased by malathion. In brain, l-arginine treatment resulted in a significantly increased malondialdehyde, decreased GSH, and increased IL-15. A significant decrease in liver malondialdehyde occurred by l-arginine/atropine or atropine. In contrast, l-arginine, l-arginine/atropine or atropine caused a significant decrease in brain and liver NO levels and increased PON-1 activity. Bcl-2 in brain significantly increased by atropine. Malathion induced brain neuronal and liver degeneration showed marked improvement after atropine alone.

Conclusions

These results indicated that exogenously administered l-arginine did not protect against the neuro- and hepto-toxic effects of malathion. Meanwhile, the ability of atropine to mitigate the deleterious effects of a toxic dose of malathion provides a strong support to the role of excessive stimulation cholinergic pathways in inflicting such damage.

Keywords: organophosphates; cholinesterase; nitric oxide; l-arginine; malathion; neuronal injury & liver damage
Corresponding author: Eman R. Youness, Department of Medical Biochemistry, Medical Research and Clinical Studies Institute, National Research Centre, Cairo, Egypt, E-mail:

Acknowledgments

We thank National Research Centre

  1. Research ethics: All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. The National rules regarding animal welfare: U.S. National Institutes of Health’s Guide for Care and Use of Laboratory Animals’ requirements (Publication No. 85-23, revised 1996) were followed.

  2. Informed consent: Not applicable.

  3. Author contributions: AS conceived the study, HF collected the data, ERY, HF did the biochemical analysis and the plagiarism. OAS wrote the manuscript. All authors reviewed, and proofread the final manuscript.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: None.

  6. Research funding: None.

  7. Data availability: The data and materials used in this study are available upon request from the authors.

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Received: 2025-05-31
Accepted: 2025-10-12
Published Online: 2025-10-28

© 2025 Walter de Gruyter GmbH, Berlin/Boston

https://doi.org/10.1515/jcim-2025-0192
Keywords for this article
organophosphates; cholinesterase; nitric oxide; l-arginine; malathion; neuronal injury & liver damage
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