Gut Inflammation Induced by Finasteride Withdrawal: Therapeutic Effect of Allopregnanolone in Adult Male Rats
by Silvia Diviccaro,Silvia Giatti, Lucia Cioffi, Eva Falvo, Monika Herian, Donatella Caruso and Roberto Cosimo Melcangi *
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milan, Italy
*Author to whom correspondence should be addressed.
Academic Editor: Monique Vallée
Biomolecules 2022, 12(11), 1567; https://doi.org/10.3390/biom12111567
Received: 23 September 2022 / Revised: 21 October 2022 / Accepted: 22 October 2022 / Published: 26 October 2022
The treatment with finasteride (i.e., an inhibitor of 5α-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-1β and TNF-α, 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.
Keywords: pro-inflammatory cytokines; serotonin; dopamine; gut steroids; pregnenolone; GABA-A receptor; post-finasteride syndrome