Induced-damages on preantral follicles by withanolide D, a potent chemotherapy candidate are not attenuated by melatonin.

Autor: Palomino GJQ; Faculty of Veterinary Medicine, Laboratory of Manipulation of Oocyte and Preantral Follicles (LAMOFOPA), State University of Ceará, Av. Dr. Silas Munguba, 1700, Fortaleza, CE, CEP: 60714-903, Brazil., Sá NAR; Faculty of Veterinary Medicine, Laboratory of Manipulation of Oocyte and Preantral Follicles (LAMOFOPA), State University of Ceará, Av. Dr. Silas Munguba, 1700, Fortaleza, CE, CEP: 60714-903, Brazil., Guerreiro DD; Faculty of Veterinary Medicine, Laboratory of Manipulation of Oocyte and Preantral Follicles (LAMOFOPA), State University of Ceará, Av. Dr. Silas Munguba, 1700, Fortaleza, CE, CEP: 60714-903, Brazil., Gomes FDR; Faculty of Veterinary Medicine, Laboratory of Manipulation of Oocyte and Preantral Follicles (LAMOFOPA), State University of Ceará, Av. Dr. Silas Munguba, 1700, Fortaleza, CE, CEP: 60714-903, Brazil., da Silva RF; Faculty of Veterinary Medicine, Laboratory of Manipulation of Oocyte and Preantral Follicles (LAMOFOPA), State University of Ceará, Av. Dr. Silas Munguba, 1700, Fortaleza, CE, CEP: 60714-903, Brazil., Lopes EPF; Faculty of Veterinary Medicine, Laboratory of Manipulation of Oocyte and Preantral Follicles (LAMOFOPA), State University of Ceará, Av. Dr. Silas Munguba, 1700, Fortaleza, CE, CEP: 60714-903, Brazil., Paes VM; Faculty of Veterinary Medicine, Laboratory of Manipulation of Oocyte and Preantral Follicles (LAMOFOPA), State University of Ceará, Av. Dr. Silas Munguba, 1700, Fortaleza, CE, CEP: 60714-903, Brazil., Gataí PHS; Laboratory of Phytochemical Analysis of Medicinal Plants (LAFIPLAN), Brazil., Alves BG; Postgraduate Program in Animal Bioscience, Federal University of Goias, Jatai, GO, Brazil., Pessoa ODL; Laboratory of Phytochemical Analysis of Medicinal Plants (LAFIPLAN), Brazil., Figueiredo JR; Faculty of Veterinary Medicine, Laboratory of Manipulation of Oocyte and Preantral Follicles (LAMOFOPA), State University of Ceará, Av. Dr. Silas Munguba, 1700, Fortaleza, CE, CEP: 60714-903, Brazil., Rocha RMP; University of International Integration of Afro-Brazilian Lusophony (UNILAB), Brazil., Rodrigues APR; Faculty of Veterinary Medicine, Laboratory of Manipulation of Oocyte and Preantral Follicles (LAMOFOPA), State University of Ceará, Av. Dr. Silas Munguba, 1700, Fortaleza, CE, CEP: 60714-903, Brazil. Electronic address: aprrodriguespapers@gmail.com.
Jazyk: angličtina
Zdroj: Reproductive toxicology (Elmsford, N.Y.) [Reprod Toxicol] 2021 Sep; Vol. 104, pp. 125-133. Date of Electronic Publication: 2021 Jul 16.
DOI: 10.1016/j.reprotox.2021.07.005
Abstrakt: Withanolide D (WD) has been investigated as an antineoplastic drug. This study aimed to evaluate whether melatonin (MT) could attenuate toxic effects on preantral follicles enclosed in the ovarian cortex (experiment 1 - E1) or on isolated secondary follicles (experiment 2 - E2) exposed to WD. For E1, ovarian cortex was incubated for 48 h to: (1) α-MEM + ; (2) α-MEM + plus 6 μM WD; (3) α-MEM + plus 3 mmol/L MT or (4) α-MEM + plus WD and MT. For E2, secondary follicles were exposed for until 96 h in. (1) only to basic medium (α-MEM ++ /α-MEM ++ ); (2) α-MEM ++ plus 3 mmol/L MT (MT/MT); (3) α-MEM ++ until 48 h, followed by more 48 h in 6 μM WD (α-MEM ++ /WD) or (4) a pre-exposure to MT for until 48 h, followed by more 48 h of exposure to WD plus MT (MT/MT + WD). The main results obtained showed that exposure to drugs caused damage to follicular morphology (WD or WD + MT) and diameter (WD) in the ovarian cortex or in isolated follicles. In pre-antral follicles in situ, ATM expression increased in the presence of WD, MT or association. As for the secondary follicles, ATM and γH2AX were immunostained in the granulosa and theca cells and oocytes in all treatments. TAp63α was immunostained in follicles included in the ovarian cortex and in isolated follicles. We conclude that melatonin did not provide protection and could have enhanced the toxic effect of WD to follicles surrounded or not by the ovarian cortex.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE