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Alcohol spiked with zolpidem and midazolam potentiates inflammation, oxidative stress and organ damage in a mouse model

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Abstract

Purpose

Crime-related spiking of alcoholic drinks with prescription drugs is quite common and has been happening for centuries. This study, therefore, evaluated the effects of oral administration of alcohol spiked with the zolpidem and midazolam potent sedatives on inflammation, oxidative stress and various organ damage in male Swiss albino mice.

Methods

Mice were randomly assigned into six treatment groups; the first group constituted the normal control, the second group received 50 mg/kg body weight of zolpidem only, the third group received 50 mg/kg body weight zolpidem dissolved in 5 g/kg alcohol, the fourth group received 50 mg/kg midazolam only, the fifth group received midazolam (50 mg/kg) dissolved in 5 g/kg alcohol and the sixth group received 5 g/kg alcohol.

Results

Alcohol-induced significant reduction in neurological function and altered blood hematological indicators. Such neurological impairment and negative effects on blood were exacerbated in mice administered with spiked alcohol. Additionally, midazolam and zolpidem enhanced alcohol-driven elevation of liver function markers; the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) gamma glutamyltransferase (GGT), total bilirubin and alkaline phosphatase. Exposure to alcohol and/or spiked alcohol led to significant augmentation of nitric oxide and malonaldehyde, with concomitant depletion of liver glutathione (GSH) levels. Similarly, serum levels of pro-inflammatory cytokines tumor necrosis factor alpha and interferon-gamma were increased by co-exposure with midazolam or zolpidem. Alcohol-induced hepatotoxicity and nephrotoxicity were amplified by exposure to alcohol spiked with midazolam/zolpidem.

Conclusion

Exposure to alcohol spiked with midazolam or zolpidem appears to exacerbate neurological deficits, inflammation, oxidative stress, and organ damage.

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Acknowledgements

Authors are grateful for the Department Pharmaceutical Technology, School of Health Sciences and Technology of the Technical University of Kenya center for all the reagents, drugs, facilities and equipment provided.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Biochemistry and Biotechnology, Technical University of Kenya, 52428, Nairobi, 00200, Kenya

    Biwott Kipchumba, Francis Gitonga, Careen Jepchirchir, Grace Wairimu Gitau, Patrick W. Okanya, Peris Wanza Amwayi & Nyariki James Nyabuga

  2. Department of Pharmaceutical Technology, School of Health Sciences and Technology, Technical University of Kenya, 52428, Nairobi, 00200, Kenya

    Alfred Orina Isaac

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  1. Biwott Kipchumba
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  2. Francis Gitonga
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Correspondence to Nyariki James Nyabuga.

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Ethical approval

All experimental techniques and protocols involving mice were sought and approved by Institutional review for approval Committee (IRC) of the Institute of Primate Research Karen, Kenya (ISERC/08/2017). All experiments were conducted in compliance with the recommendations of Helsinki’s declaration on guiding principles on care and use of animals in biomedical research.

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Kipchumba, B., Gitonga, F., Jepchirchir, C. et al. Alcohol spiked with zolpidem and midazolam potentiates inflammation, oxidative stress and organ damage in a mouse model. Forensic Toxicol 42, 45–59 (2024). https://doi.org/10.1007/s11419-023-00674-w

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