The inhibitory effect of sodium nitroprusside and N acetyl-L-cysteine on desipramine-induced eryptosis

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Dokumentart: PhDThesis
Date: 2023-12-21
Language: English
Faculty: 4 Medizinische Fakultät
Department: Medizin
Advisor: Wieder, Thomas (Prof. Dr.)
Day of Oral Examination: 2023-12-07
DDC Classifikation: 610 - Medicine and health
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Depression is currently the most common psychiatric disorder, and its prevalence is increasing annually. One of the primary targets of tricyclic antidepressants (TCAs) among them also desipramine (Des) are serotonin and norepinephrine transporters (SERT and NET). Des interaction with NET preferentially increase norepinephrine (NE) transmission by inhibiting NE reuptake, thus relieving depressive symptoms. Overdose of Des causes systemic intoxication. Until today there is no effective treatment for this condition and many patients die yearly due to drug abuse. Therefore, further studies on Des may provide new therapeutic possibilities to combat drug abuse. Erythrocytes represent the largest cell population in our body and permanently interact with other organs. Thus, drugs changing the biological activities of erythrocytes, directly influence the whole organism. Therefore, we aimed to investigate a) the relationship between Des and eryptosis, and b) shed light on the underlying mechanisms. Experiments such as annexin V binding, hemolysis and glutathione measurement were performed to determine eryptosis, cell membrane integrity and redox status of erythrocytes after treatment with Des. Interestingly, calcium depletion led to the enhancement of Des-induced eryptosis. We also checked the possible inhibitory effects of both inhibitors the NO donor sodium nitroprusside (SNP) and N-acetyl-L-cysteine (NAC) on Des-induced eryptosis. Indeed, single treatment of erythrocytes with SNP and NAC could significantly inhibit Des-induced eryptosis and their co-treatment had the highest inhibitory effect. The most important in vitro findings of this study are: SNP and NAC are able to inhibit an ongoing Des-induced eryptosis.

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