Protective effects of exogenous melatonin therapy against oxidative stress to male reproductive tissue caused by anti-cancer chemical and radiation therapy: a systematic review and meta-analysis of animal studies.
cancer
chemotherapy
male reproduction
melatonin
radiotherapy
rodents
testicular tissue
Journal
Frontiers in endocrinology
ISSN: 1664-2392
Titre abrégé: Front Endocrinol (Lausanne)
Pays: Switzerland
ID NLM: 101555782
Informations de publication
Date de publication:
2023
2023
Historique:
received:
12
03
2023
accepted:
10
08
2023
medline:
14
9
2023
pubmed:
13
9
2023
entrez:
13
9
2023
Statut:
epublish
Résumé
Male testicular dysfunction is a considerable complication of anti-cancer therapies, including chemotherapy and radiotherapy, partly due to the increased oxidative stress caused by these treatments. Melatonin is an effective antioxidant agent that protects testicles against physical and toxic chemical stressors in animal models. This study aims to systematically review the melatonin's protective effects against anti-cancer stressors on rodential testicular tissue. An extensive search was conducted in Web of Science, Scopus, and PubMed for animal studies investigating exogenous melatonin's protective effects on rodent testicles exposed to anti-cancer chemicals and radiotherapeutic agents. Using the DerSimonian and Laird random-effect model, standardized mean differences and 95% confidence intervals were estimated from the pooled data. The protocol was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42022355293). The meta-analysis included 38 studies from 43 studies that were eligible for the review. Rats and mice were exposed to radiotherapy (ionizing radiations such as gamma- and roentgen radiation and radioactive iodine) or chemotherapy (methotrexate, paclitaxel, busulfan, cisplatin, doxorubicin, vinblastine, bleomycin, cyclophosphamide, etoposide, Taxol, procarbazine, docetaxel, and chlorambucil). According to our meta-analysis, all outcomes were significantly improved by melatonin therapy, including sperm quantity and quality (count, motility, viability, normal morphology, number of spermatogonia, Johnsen's testicular biopsy score, seminiferous tubular diameter, and seminiferous epithelial height), serum level of reproductive hormones (Follicle-Stimulating Hormone and testosterone), tissue markers of oxidative stress (testicular tissue malondialdehyde, superoxide dismutase, glutathione peroxidase, catalase, glutathione, caspase-3, and total antioxidant capacity), and weight-related characteristics (absolute body, epididymis, testis, and relative testis to body weights). Most SYRCLE domains exhibited a high risk of bias in the included studies. Also, significant heterogeneity and small-study effects were detected. In male rodents, melatonin therapy was related to improved testicular histopathology, reproductive hormones, testis and body weights, and reduced levels of oxidative markers in testicular tissues of male rodents. Future meticulous studies are recommended to provide a robust scientific backbone for human applications. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022355293, identifier CRD42022355293.
Sections du résumé
Background
Male testicular dysfunction is a considerable complication of anti-cancer therapies, including chemotherapy and radiotherapy, partly due to the increased oxidative stress caused by these treatments. Melatonin is an effective antioxidant agent that protects testicles against physical and toxic chemical stressors in animal models. This study aims to systematically review the melatonin's protective effects against anti-cancer stressors on rodential testicular tissue.
Materials and Method
An extensive search was conducted in Web of Science, Scopus, and PubMed for animal studies investigating exogenous melatonin's protective effects on rodent testicles exposed to anti-cancer chemicals and radiotherapeutic agents. Using the DerSimonian and Laird random-effect model, standardized mean differences and 95% confidence intervals were estimated from the pooled data. The protocol was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42022355293).
Results
The meta-analysis included 38 studies from 43 studies that were eligible for the review. Rats and mice were exposed to radiotherapy (ionizing radiations such as gamma- and roentgen radiation and radioactive iodine) or chemotherapy (methotrexate, paclitaxel, busulfan, cisplatin, doxorubicin, vinblastine, bleomycin, cyclophosphamide, etoposide, Taxol, procarbazine, docetaxel, and chlorambucil). According to our meta-analysis, all outcomes were significantly improved by melatonin therapy, including sperm quantity and quality (count, motility, viability, normal morphology, number of spermatogonia, Johnsen's testicular biopsy score, seminiferous tubular diameter, and seminiferous epithelial height), serum level of reproductive hormones (Follicle-Stimulating Hormone and testosterone), tissue markers of oxidative stress (testicular tissue malondialdehyde, superoxide dismutase, glutathione peroxidase, catalase, glutathione, caspase-3, and total antioxidant capacity), and weight-related characteristics (absolute body, epididymis, testis, and relative testis to body weights). Most SYRCLE domains exhibited a high risk of bias in the included studies. Also, significant heterogeneity and small-study effects were detected.
Conclusion
In male rodents, melatonin therapy was related to improved testicular histopathology, reproductive hormones, testis and body weights, and reduced levels of oxidative markers in testicular tissues of male rodents. Future meticulous studies are recommended to provide a robust scientific backbone for human applications.
Systematic review registration
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022355293, identifier CRD42022355293.
Identifiants
pubmed: 37701901
doi: 10.3389/fendo.2023.1184745
pmc: PMC10494246
doi:
Substances chimiques
Melatonin
JL5DK93RCL
Antioxidants
0
Iodine Radioisotopes
0
Types de publication
Meta-Analysis
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1184745Informations de copyright
Copyright © 2023 Dehdari Ebrahimi, Sadeghi, Shojaei-Zarghani, Shahlaee, Taherifard, Rahimian, Eghlidos, Azarpira and Safarpour.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Fertil Steril. 2019 Jun;111(6):1129-1134
pubmed: 30982604
Theriogenology. 2020 Jun;149:25-37
pubmed: 32234648
Andrologia. 2018 Feb 11;:
pubmed: 29430687
Biophys Rev. 2017 Apr;9(2):139-148
pubmed: 28510090
Endocrinology. 1984 Dec;115(6):2303-10
pubmed: 6499770
Cell Biol Toxicol. 2003 Nov;19(6):367-72
pubmed: 15015761
BMC Med Res Methodol. 2014 Mar 26;14:43
pubmed: 24667063
J Pharm Bioallied Sci. 2021 Apr-Jun;13(2):268-275
pubmed: 34349489
Syst Biol Reprod Med. 2014 Dec;60(6):323-8
pubmed: 25140409
J Cell Physiol. 2019 Sep;234(9):14828-14837
pubmed: 30740683
Antioxidants (Basel). 2020 Dec 14;9(12):
pubmed: 33327643
Res Synth Methods. 2020 Sep;11(5):641-654
pubmed: 32562361
Eur Rev Med Pharmacol Sci. 2018 Nov;22(21):7517-7525
pubmed: 30468501
J Biomed Sci. 2015 Jul 24;22:61
pubmed: 26205951
World J Mens Health. 2020 Oct;38(4):484-494
pubmed: 31385474
Free Radic Res. 2020 Jan;54(1):1-26
pubmed: 31868060
Cells. 2022 May 19;11(10):
pubmed: 35626727
Front Cell Dev Biol. 2022 May 12;10:877079
pubmed: 35646894
Andrologia. 2020 Dec;52(11):e13834
pubmed: 33040351
Andrologia. 2019 Sep;51(8):e13320
pubmed: 31131920
Stat Methods Med Res. 2018 Jun;27(6):1785-1805
pubmed: 27683581
Biomed Pharmacother. 2021 Jun;138:111481
pubmed: 33752059
Life Sci. 2004 Jul 2;75(7):765-90
pubmed: 15183071
Urology. 2022 Nov;169:92-95
pubmed: 35963395
BMJ. 2021 Mar 29;372:n71
pubmed: 33782057
Front Endocrinol (Lausanne). 2023 Jul 05;14:1202560
pubmed: 37476491
Andrology. 2016 May;4(3):526-41
pubmed: 27037637
CA Cancer J Clin. 2021 May;71(3):209-249
pubmed: 33538338
World J Mens Health. 2019 May;37(2):166-174
pubmed: 30588779
J Pharm Pharmacol. 2018 Mar;70(3):291-306
pubmed: 29168173
Hepatology. 2021 Sep;74(3):1611-1644
pubmed: 34233031
Front Endocrinol (Lausanne). 2018 Dec 14;9:763
pubmed: 30619093
Braz J Med Biol Res. 2009 Jul;42(7):621-8
pubmed: 19578641
Mol Cell Endocrinol. 2020 Sep 15;515:110889
pubmed: 32622722
Int J Reprod Biomed. 2017 Jul;15(7):403-412
pubmed: 29202124
Hum Exp Toxicol. 2014 Feb;33(2):185-95
pubmed: 23703819
Iran Red Crescent Med J. 2014 Feb;16(2):e14463
pubmed: 24719743
Int J Mol Sci. 2019 Feb 22;20(4):
pubmed: 30813253
Drug Chem Toxicol. 2016;39(2):137-46
pubmed: 26072956
Free Radic Biol Med. 2019 Jun;137:74-86
pubmed: 30986493
Redox Rep. 2003;8(4):205-13
pubmed: 14599344
Sleep Med. 2019 Mar;55:14-21
pubmed: 30743205
Biol Reprod. 2021 Jun 4;104(6):1322-1336
pubmed: 33709108
Int J Reprod Biomed. 2020 Dec 21;18(12):1073-1080
pubmed: 33426418
Front Endocrinol (Lausanne). 2023 Jan 30;14:1119553
pubmed: 36793277
BMJ. 1997 Sep 13;315(7109):629-34
pubmed: 9310563
Endocrine. 2018 Oct;62(1):242-249
pubmed: 29797213
Toxicology. 2022 May 15;473:153193
pubmed: 35533795
Front Endocrinol (Lausanne). 2023 Jan 31;14:1123999
pubmed: 36798664
Fertil Steril. 2006 Sep;86(3):750-2
pubmed: 16854416
JBRA Assist Reprod. 2021 Apr 27;25(2):176-184
pubmed: 33507719
Fertil Steril. 2009 Sep;92(3):1124-1132
pubmed: 18829000
Reprod Biol Endocrinol. 2022 Jul 18;20(1):105
pubmed: 35850689
Braz J Med Biol Res. 2022 Feb 04;55:e11614
pubmed: 35137851
Biotech Histochem. 2017;92(8):552-559
pubmed: 29161153
Front Mol Biosci. 2022 Jan 05;8:799294
pubmed: 35071326
J Reprod Infertil. 2015 Jul-Sep;16(3):123-9
pubmed: 26913230
J Gastroenterol Hepatol. 2019 Dec;34(12):2062-2070
pubmed: 31254469
Vitam Horm. 2023;121:197-246
pubmed: 36707135
J Cell Mol Med. 2022 Feb;26(4):1219-1228
pubmed: 35001532
Syst Rev. 2016 Dec 5;5(1):210
pubmed: 27919275
Reprod Sci. 2022 Mar;29(3):944-954
pubmed: 34642916
Cell Mol Biol Lett. 2019 Mar 12;24:21
pubmed: 30915128
Andrologia. 2018 Nov;50(9):e13077
pubmed: 30019386
Hum Reprod. 2011 Oct;26(10):2799-806
pubmed: 21775336
J Pineal Res. 2006 Aug;41(1):21-7
pubmed: 16842537
Acta Biochim Pol. 2003;50(4):1129-46
pubmed: 14740000
Andrologia. 2012 May;44 Suppl 1:796-803
pubmed: 22212014
Cell Physiol Biochem. 2017;44(6):2407-2421
pubmed: 29268276
Biol Reprod. 2021 Nov 15;105(5):1307-1316
pubmed: 34363387
Oxid Med Cell Longev. 2020 May 21;2020:6841581
pubmed: 32566095
Fertil Steril. 2013 Nov;100(5):1180-6
pubmed: 24012199
Hum Reprod. 2000 Jan;15(1):60-5
pubmed: 10611189
Int J Reprod Biomed. 2020 May 31;18(5):327-338
pubmed: 32637861
Endocrine. 1999 Jun;10(3):201-17
pubmed: 10484284
Exp Mol Pathol. 2020 Feb;112:104324
pubmed: 31697930
Biomed Pharmacother. 2021 Oct;142:112040
pubmed: 34416630
Acta Oncol. 2007;46(4):480-9
pubmed: 17497315