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

Abstract

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.

Crocetin Mitigates Irradiation Injury in an In Vitro Model of the Pubertal Testis: Focus on Biological Effects and Molecular Mechanisms

“…The crocetin supplementation was able to restore the basal levels of SOD2, CAT and HuR but had no effects on SIRT1 expression following IR ( Figure 3 ). The establishment of a condition of oxidative stress in IR testes was confirmed by evaluating lipid peroxidation [ 41 , 42 ]. As shown in Supplementary Figure S1 , IR insult induced a significant increase in 4-HNE immunostaining, which was prevented by medium supplementation with crocetin.…”

“…The observation that crocetin exposure was effective in maintaining basal protein levels of SOD2 and CAT during IR supports the hypothesis that radioprotective activity of crocetin is mediated by its ROS scavenging activity or modulation of antioxidants genes [ 31 , 48 , 50 , 51 , 52 ]. A further evidence is the observation in testes cultured in the presence of crocetin prior and after irradiation of a reduction of oxidative damage measured by levels of 4-HNE, a well-known marker of lipid peroxidation [ 42 ].…”

A Novel Bilayer Propionyl-L-carnitine Loaded Polyvinyl Alcohol/Calcium Alginate/Carboxymethyl Cellulose wound dressing for the treatment of diabetic wounds: an in vitro and in vivo study

“…This substance is an ester of L-carnitine which is essential in fatty acids metabolism. Furthermore, it has been shown that Propionyl-L-carnitine is an antioxidant agent and can prevent lipid peroxidation in elevated levels of reactive oxygen species (Di Emidio et al 2020).…”

Short‐term rapamycin administration elevated testosterone levels and exacerbated reproductive disorder in dehydroepiandrosterone‐induced polycystic ovary syndrome mice

“…Vaginal smears were collected on glass slides in 30 µL of PBS and then observed directly under a light microscope with a 10× objective [ 14 ]. The four stages of the estrous cycle were determined as previously described by analyzing the proportion of three major cell types (epithelial cells, cornified cells, and leukocytes) [ 15 ].…”