In vivo exposure to a new 2-cyano-2-p-nitrophenyl-N-benzylthioamide decreases doxorubicin-triggered structural damages in the mature testis.

Autor: Boussada M; Research Unit 17/ES/13, Laboratory of Histology and Embryology, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia., Hammami I; Research Unit 17/ES/13, Laboratory of Histology and Embryology, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia., Ben Ali R; Research Unit 17/ES/13, Laboratory of Histology and Embryology, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia.; Experimental Medicine Unit, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia., Ammar AB; Laboratory of Electronic Microscopy, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia., Alves M; Department of Microscopy, Laboratory of Cell Biology, Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal., Oliveira PF; Department of Microscopy, Laboratory of Cell Biology, Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.; i3S, Instituto de Investigação e Inovação da Universidade do Porto, Porto, Portugal.; Department of Genetics, Faculty of Medicine, University of Porto, Porto, Portugal., Akacha AB; Laboratory of Organic Synthesis and Heterocyclic Chemistry Department, School of Sciences of Tunis, University of Tunis El Manar, Tunis, Tunisia., Abdelkarim IL; Laboratory oh Hematology, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia., Zekri S; Laboratory of Electronic Microscopy, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia., El May MV; Research Unit 17/ES/13, Laboratory of Histology and Embryology, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia.
Jazyk: angličtina
Zdroj: Andrologia [Andrologia] 2022 Dec; Vol. 54 (11), pp. e14634. Date of Electronic Publication: 2022 Nov 10.
DOI: 10.1111/and.14634
Abstrakt: The use of doxorubicin (DOX) in clinical practice continues to be challenged by its severe toxicity. DOX cytotoxic activity is not only directed against malignant tumours, given that the treatment will damage healthy tissues as well leading to irreversible injuries. This study aimed to address the in vivo effects of DOX and its co-administration with a new analog of thioamide; thiocyanoacetamide (TA) on the germinal epithelium. Thus, male rats received either intravenous injection (iv) of 0.03 mg/kg of body weight/week, 0.9% NaCl and were regarded as the control group (CTR), treated with DOX (3.7 mg/kg/week iv), TA [10 mg/kg/day intragastrically (ig)] or a co-supplementation of DOX and TA. After 50 days, the left testes were dissected and used for toluidine blue, periodic acid-Schiff (PAS) staining (to evaluate the change in polysaccharides/glycoproteins content), and transmission electron microscopy (TEM) (to assess the morphological damages). To estimate the impact of the test compounds on mitochondrial biogenesis, the expression of NAD-dependent deacetylase sirtuin-3 (SIRT-3) and proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) were evaluated by immunofluorescence. Apoptotic cells were observed using Hoechst 33324 fluorescent staining. Data showed testicular injuries in the DOX-treated group, manifested by a significant decrease in total germ cell (GC) number, alteration of Sertoli cell (SC) nucleolus, anchoring junction, along with modifications of the basement membrane (BM) regularity and increase in apoptotic cell count. Mitochondrial aspect and SIRT-3 and PGC-1α expression in the testis were unaffected by the DOX. Co-therapy increased GC number, decreased apoptotic cell count, and restored the BM and anchoring junction regular aspects. This study provides novel insights into understanding DOX-mediated impairment in rats' testis and might offer some basis for the emerging new alternative therapeutic schemes in male patients undergoing chemotherapy.
(© 2022 Wiley-VCH GmbH.)
Databáze: MEDLINE
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