The treatment with finasteride (i.e., an inhibitor of 5a-reductase) may be associated with different side effects (i.e., depression, anxiety, cognitive impairment and sexual dysfunction) inducing the so-called post finasteride syndrome (PFS). Moreover, previous observations in PFS patients and an experimental model showed alterations in gut microbiota populations, suggesting an inflammatory environment. To confirm this hypothesis, we have explored the effect of chronic treatment with finasteride (i.e., for 20 days) and its withdrawal (i.e., for 1 month) on the levels of steroids, neurotransmitters, pro-inflammatory cytokines and gut permeability markers in the colon of adult male rat. The obtained data demonstrate that the levels of allopregnanolone (ALLO) decreased after finasteride treatment and after its withdrawal. Following the drug suspension, the decrease in ALLO levels correlates with an increase in IL-1 beta and TNF-alpha, serotonin and a decrease in dopamine. Importantly, ALLO treatment is able to counteract some of these alterations. The relation between ALLO and GABA-A receptors and/or pregnenolone (ALLO precursor) could be crucial in their mode of action. These observations provide an important background to explore further the protective effect of ALLO in the PFS experimental model and the possibility of its translation into clinical therapy.

Gut Inflammation Induced by Finasteride Withdrawal: Therapeutic Effect of Allopregnanolone in Adult Male Rats / S. Diviccaro, S. Giatti, L. Cioffi, E. Falvo, M. Herian, D. Caruso, R.C. Melcangi. - In: BIOMOLECULES. - ISSN 2218-273X. - 12:11(2022 Nov), pp. 1567.1-1567.21. [10.3390/biom12111567]

Gut Inflammation Induced by Finasteride Withdrawal: Therapeutic Effect of Allopregnanolone in Adult Male Rats

S. Diviccaro
Primo
;
S. Giatti;L. Cioffi;E. Falvo;D. Caruso;R.C. Melcangi
Ultimo
2022

Abstract

The treatment with finasteride (i.e., an inhibitor of 5a-reductase) may be associated with different side effects (i.e., depression, anxiety, cognitive impairment and sexual dysfunction) inducing the so-called post finasteride syndrome (PFS). Moreover, previous observations in PFS patients and an experimental model showed alterations in gut microbiota populations, suggesting an inflammatory environment. To confirm this hypothesis, we have explored the effect of chronic treatment with finasteride (i.e., for 20 days) and its withdrawal (i.e., for 1 month) on the levels of steroids, neurotransmitters, pro-inflammatory cytokines and gut permeability markers in the colon of adult male rat. The obtained data demonstrate that the levels of allopregnanolone (ALLO) decreased after finasteride treatment and after its withdrawal. Following the drug suspension, the decrease in ALLO levels correlates with an increase in IL-1 beta and TNF-alpha, serotonin and a decrease in dopamine. Importantly, ALLO treatment is able to counteract some of these alterations. The relation between ALLO and GABA-A receptors and/or pregnenolone (ALLO precursor) could be crucial in their mode of action. These observations provide an important background to explore further the protective effect of ALLO in the PFS experimental model and the possibility of its translation into clinical therapy.
GABA-A receptor; dopamine; gut steroids; post-finasteride syndrome; pregnenolone; pro-inflammatory cytokines; serotonin
Settore MED/13 - Endocrinologia
Settore BIO/10 - Biochimica
   Medicina personalizzata per strategie innovative in malattie neuro-psichiatriche e vascolari (PerMedNet)
   PerMedNet
   MINISTERO DELL'ISTRUZIONE E DEL MERITO
   ARS01_01226
nov-2022
26-ott-2022
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/964136
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