Apoptotic Effect of Long-term Administration of Antidepressant Duloxetine on the Tongue of Albino Rats: Histological and Immuno-histochemical Study

Introduction: Depression is one of the most common causes of loss of health and productivity and inability to work. Duloxetine (Cymbalta) is an antidepressant drug that belongs to the class of Serotonin–norepinephrine reuptake inhibitors (SNRIs),  which is used for the treatment of major depressive disorder (MDD). In addition, this class is used for the treatment of anxiety disorders. One of the members of the bcl-2 family is the BAX (BCL2 Associated X, Apoptosis Regulator) and it has a key role in the mitochondrial apoptotic process. Under stress conditions, Bax undergoes a conformation change that triggers apoptosis.
Objectives: This study aimed to examine the possible impact of long term administration of antidepressant duloxetine on the oral mucosa and salivary glands in tongue.
Material & methods: Twenty adult male albino rats were divided into two equal groups. Group one served as control group. Group two served as treated group which received duloxetine dissolved in distilled water in a daily oral dose of 10 mg/kg body weight using a curved metallic oro-pharyngeal tube. At the end of the experiment which lasted for three months, the rats were euthanized by cervical dislocation. Tissue samples were fixed in 10% formalin, embedded in paraffin, and stained with hematoxylin and eosin to evaluate histopathological finding. Masson’ trichrome for collagen detection. Other sections were used to reveal the immuno-histochemical expression of Bax antibodies through computerized image j analysis software. The expression of the marker was analyzed statistically using Mann-Whitney test.
Results: Histopathological finding of long term administration of duloxetine treated animals showed noticeable atrophic and degenerative changes in the surface epithelium and lamina propria of both the dorsal and ventral surfaces of the tongue as well as the lingual salivary gland. Immuno-histochemical finding revealed marked increase in the expression of Bax all over the epithelial cells as well as fibroblast, blood vessels and the lingual salivary glands in the lamina propria. Statistical finding in duloxetine treated animals showed highly significant difference in the expression of Bax.
Conclusion: Although duloxetine being useful drug in treatment depression, anxiety and severe pain, it harmfully affected the histological structure of oral mucosa and salivary glands of the tongue in adult rats. Accordingly using of these drugs should be under supervision and strong caution.