Regulatory Functions of L-Carnitine, Acetyl, and Propionyl L-Carnitine in a PCOS Mouse Model: Focus on Antioxidant/Antiglycative Molecular Pathways in the Ovarian Microenvironment

Giovanna Di Emidio; Francesco Rea; Martina Placidi; Giulia Rossi; Domenica Cocciolone; Ashraf Virmani; Guido Macchiarelli; Maria Grazia Palmerini; Anna Maria D’Alessandro; Paolo Giovanni Artini; Carla Tatone

doi:10.3390/antiox9090867

Antioxidants (Sep 2020)

Regulatory Functions of L-Carnitine, Acetyl, and Propionyl L-Carnitine in a PCOS Mouse Model: Focus on Antioxidant/Antiglycative Molecular Pathways in the Ovarian Microenvironment

Giovanna Di Emidio,
Francesco Rea,
Martina Placidi,
Giulia Rossi,
Domenica Cocciolone,
Ashraf Virmani,
Guido Macchiarelli,
Maria Grazia Palmerini,
Anna Maria D’Alessandro,
Paolo Giovanni Artini,
Carla Tatone

Affiliations

Giovanna Di Emidio: Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy
Francesco Rea: Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy
Martina Placidi: Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy
Giulia Rossi: Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy
Domenica Cocciolone: Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy
Ashraf Virmani: Alfasigma Health Science, 3528 BG Utrecht, The Netherlands
Guido Macchiarelli: Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy
Maria Grazia Palmerini: Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy
Anna Maria D’Alessandro: Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy
Paolo Giovanni Artini: Department of Obstetrics and Gynecology “P. Fioretti” University of Pisa, 56126 Pisa, Italy
Carla Tatone: Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy

DOI: https://doi.org/10.3390/antiox9090867
Journal volume & issue: Vol. 9, no. 9
p. 867

Abstract

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Polycystic ovary syndrome (PCOS) is a complex metabolic disorder associated with female infertility. Based on energy and antioxidant regulatory functions of carnitines, we investigated whether acyl-L-carnitines improve PCOS phenotype in a mouse model induced by dehydroepiandrosterone (DHEA). CD1 mice received DHEA for 20 days along with two different carnitine formulations: one containing L-carnitine (LC) and acetyl-L-carnitine (ALC), and the other one containing also propionyl-L-carnitine (PLC). We evaluated estrous cyclicity, testosterone level, ovarian follicle health, ovulation rate and oocyte quality, collagen deposition, lipid droplets, and 17ß-HSD IV (17 beta-hydroxysteroid dehydrogenase type IV) expression. Moreover, we analyzed protein expression of SIRT1, SIRT3, SOD2 (superoxide dismutase 2), mitochondrial transcriptional factor A (mtTFA), RAGE (receptor for AGEs), GLO2 (glyoxalase 2) and ovarian accumulation of MG-AGEs (advanced glycation end-products formed by methylglyoxal). Both carnitine formulations ameliorated ovarian PCOS phenotype and positively modulated antioxidant molecular pathways in the ovarian microenvironment. Addition of PLC to LC-ALC formulation mitigated intraovarian MG-AGE accumulation and increased mtTFA expression. In conclusion, our study supports the hypothesis that oral administration of acyl-L-carnitines alleviates ovarian dysfunctions associated with this syndrome and that co-administration of PLC provides better activity. Molecular mechanisms underlying these effects include anti-oxidant/glycative activity and potentiation of mitochondria.

Published in Antioxidants

ISSN: 2076-3921 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://www.mdpi.com/journal/antioxidants

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