The effect of codeine administration on oxidative stress biomarkers and the expression of the neuron-specific enolase in the brain of Wistar rats.

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.