Abstract
The study aimed to assess the effects of codeine medication on some oxidative stress parameters and how it affects the expression of enolase in neuronal cells. The codeine medication used for the study was Archilin™ with codeine syrup and dihydrocodeine 30 mg. The study used 30 male Wistar rats which were grouped in five: A, B, C, D, and E (n = 6), while treatments were administered for 21 days. Based on the LD50s of 6.09 ml/kg body weight (b.wt.) Archilin™ with codeine syrup and 3.145 mg/kg b.wt. dihydrocodeine, group A served as control and were given normal saline; groups B and C were treated with 1 mg/kg and 2 mg/kg b.wt. dihydrocodeine, respectively; while groups D and E were treated with 2 ml/kg and 4 ml/kg b.wt. Archilin™ with codeine syrup, respectively. After treatments, animals were sacrificed via cervical dislocation and the brains were harvested and prepared for determination of oxidative stress biomarkers as well as immunohistochemical studies of neuron-specific enolase (NSE) to assess for neuronal cell integrity. Significantly decreased mean values (p < 0.05) of superoxide dismutase (SOD) and catalase (CAT) activities were observed while malondialdehyde (MDA) is significantly increased (p < 0.05) among treated groups. The expression of enolase was downregulated in treatment groups when compared to control. Animals in group A which are control showed strong staining intensity of the prefrontal cortex compared to groups C, D, and E which showed mild staining. The scoring of group A for cerebellum showed strong staining intensity, groups B and C showed mild staining, while groups D and E showed weak staining intensity. From the findings of this study, prolonged codeine syrup administration causes oxidative stress and this affects the expression of enolase in neuronal cells resulting in glucose hypometabolism which eventually results in functional brain failure.
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Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Code availability
The data obtained from this study were subjected to a two-way analysis of variance using the SPSS statistical analysis software (SPSS-20®).
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Acknowledgements
The authors are grateful to the Head of Department and staff members of the Department of Anatomy, Heads of Laboratories of Anatomy and Biochemistry, and Officer in Charge of the animal house, Faculty of Basic Medical Sciences, University of Calabar, Calabar, Nigeria, for their support towards the success of this study.
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TE, AI, and VBA contributed to the study conception and research design. The study was supervised by TE and AI while the material preparation, data collection, and analysis were performed by VBA, EOO, and JEI. The first draft of the manuscript was written by JEI, and all authors read and reviewed the initial versions of the manuscript. All authors approved the final manuscript herein submitted. The authors declare that all data were generated in-house and that no paper mill was used.
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Approval was sought and obtained from the Faculty of Basic Medical Sciences Ethics Committee of the University of Calabar, Calabar, Nigeria (Approval no. 008AN30418). The animals were handled according to the guidelines of the National Institutes of Health (NIH), USA, for the handling of laboratory animals (Institute Animal Care and Use Committee, 2015). Consent to participate is not applicable.
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Archibong, V.B., Ekanem, T., Igiri, A. et al. The effect of codeine administration on oxidative stress biomarkers and the expression of the neuron-specific enolase in the brain of Wistar rats. Naunyn-Schmiedeberg's Arch Pharmacol 394, 1665–1673 (2021). https://doi.org/10.1007/s00210-021-02094-2
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DOI: https://doi.org/10.1007/s00210-021-02094-2