l-carnitine reduces the adverse effects of ROS and up-regulates the expression of implantation related genes in in vitro developed mouse embryos

Shafiei, Golnaz; Almasi, Majid; Nikzad, Hossein; Miyan, Jaleel; Mahabadi, Javad Amini; Moshkdanian, Ghazaleh

doi:10.1016/j.theriogenology.2020.01.008

Cited by 16 publications

(3 citation statements)

References 36 publications

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“…Administration of acyl-L-carnitines in DHEA-induced-PCOS mice promoted mitochondrial replication and reduced glycative stress making unnecessary the activation of SIRT3-SOD2 antioxidant response [126]. Similarly, L-carnitine supplementation in medium of mouse oocytes matured in vitro after a mild oxidative stress prevented Sirt3 rise [127]. By contrast oocytes from PCOS mice obtained after a single injection of estradiol valerate presented a low level of Sirt3 gene expression, that was reverted by in vivo administration of metformin, but not clomiphene citrate [128].…”

Section: Sirtuins Mitochondria and Female Reproductionmentioning

confidence: 99%

Mitochondrial Sirtuins in Reproduction

et al. 2021

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Mitochondria act as hubs of numerous metabolic pathways. Mitochondrial dysfunctions contribute to altering the redox balance and predispose to aging and metabolic alterations. The sirtuin family is composed of seven members and three of them, SIRT3-5, are housed in mitochondria. They catalyze NAD+-dependent deacylation and the ADP-ribosylation of mitochondrial proteins, thereby modulating gene expression and activities of enzymes involved in oxidative metabolism and stress responses. In this context, mitochondrial sirtuins (mtSIRTs) act in synergistic or antagonistic manners to protect from aging and aging-related metabolic abnormalities. In this review, we focus on the role of mtSIRTs in the biological competence of reproductive cells, organs, and embryos. Most studies are focused on SIRT3 in female reproduction, providing evidence that SIRT3 improves the competence of oocytes in humans and animal models. Moreover, SIRT3 protects oocytes, early embryos, and ovaries against stress conditions. The relationship between derangement of SIRT3 signaling and the imbalance of ROS and antioxidant defenses in testes has also been demonstrated. Very little is known about SIRT4 and SIRT5 functions in the reproductive system. The final goal of this work is to understand whether sirtuin-based signaling may be taken into account as potential targets for therapeutic applications in female and male infertility.

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Section: Sirtuins Mitochondria and Female Reproductionmentioning

confidence: 99%

Mitochondrial Sirtuins in Reproduction

et al. 2021

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“…Previous reports have demonstrated that l -carnitine is involved in the antioxidant effect against reactive oxygen species in hepatocytes, 29 proximal tubule epithelial cells, 30 lens epithelial cells, 31 ovary cells, 32 and mouse embryos. 33 l -Carnitine effectively diminishes H 2 O 2 -induced cell apoptosis 33 by stabilizing antioxidant proteins such as superoxidase dismutase. 34 Fundamentally, l -carnitine increases fatty acid transfer into mitochondria and stimulates fatty acid β-oxidation, which potentially generates reactive oxygen species; therefore, it could be assumed that l -carnitine might also be involved in reactive oxygen species removal pathways.…”

Section: Discussionmentioning

confidence: 99%

Potential utility of l-carnitine for preventing liver tumors derived from metabolic dysfunction–associated steatohepatitis

Lyu,

Okada,

Sunagozaka

et al. 2024

Hepatology Communications

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Background: Recent reports have unveiled the potential utility of l-carnitine to alleviate metabolic dysfunction–associated steatohepatitis (MASH) by enhancing mitochondrial metabolic function. However, its efficacy at preventing the development of HCC has not been assessed fully. Methods: l-carnitine (2 g/d) was administered to 11 patients with MASH for 10 weeks, and blood liver function tests were performed. Five patients received a serial liver biopsy, and liver histology and hepatic gene expression were evaluated using this tissue. An atherogenic plus high-fat diet MASH mouse model received long-term l-carnitine administration, and liver histology and liver tumor development were evaluated. Results: Ten-week l-carnitine administration significantly improved serum alanine transaminase and aspartate transaminase levels along with a histological improvement in the NAFLD activity score, while steatosis and fibrosis were not improved. Gene expression profiling revealed a significant improvement in the inflammation and profibrotic gene signature as well as the recovery of lipid metabolism. Long-term l-carnitine administration to atherogenic plus high-fat diet MASH mice substantially improved liver histology (inflammation, steatosis, and fibrosis) and significantly reduced the incidence of liver tumors. l-carnitine directly reduced the expression of the MASH-associated and stress-induced transcriptional factor early growth response 1. Early growth response 1 activated the promoter activity of neural precursor cell expressed, developmentally downregulated protein 9 (NEDD9), an oncogenic protein. Thus, l-carnitine reduced the activation of the NEDD9, focal adhesion kinase 1, and AKT oncogenic signaling pathway. Conclusions: Short-term l-carnitine administration ameliorated MASH through its anti-inflammatory effects. Long-term l-carnitine administration potentially improved the steatosis and fibrosis of MASH and may eventually reduce the risk of HCC.

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“…Studies have shown that when sperm move from the head to the tail of the epididymis, LC can reduce lipid content on the sperm membrane, and increase the ratio of saturated fatty acids, unsaturated fatty acids, cholesterol, and congealed fat, causing changes in membrane composition and structure and maintaining fluidity of the sperm membrane (7). Other reports have shown that LC has an antioxidant effect, can inhibit the production of reactive oxygen species, avoid sperm oxidative damage, and effectively maintain the normal physiological function of sperm (12,13). LC is one of the preferred drugs for the treatment of male infertility, and has a certain curative effect on oligozoospermia, asthenospermia, and teratozoospermia.…”

Section: Discussionmentioning

confidence: 99%

Effects of L-carnitine combined with pancreatic kininogenase on thioredoxin 2, thioredoxin reductase 1, and sperm quality in patients with oligoasthenospermia

et al. 2021

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Background: To study the effects of L-carnitine (LC) combined with pancreatic kininogenase on thioredoxin 2 (Trx 2), thioredoxin reductase 1 (TrxR 1), and sperm quality in patients with oligoasthenospermia.Methods: A total of 300 male infertility patients with oligoasthenospermia who were treated in the andrology clinic of our hospital from December 2019 to December 2020 were randomly divided into an LC group and combined treatment group, and 50 males with normal semen were selected as a control group.The computer-assisted semen analysis system (CASA) was used to detect the total number, vitality, and forward motility of the sperm before and after treatment, and sperm morphology was detected by the Diff-Quik method of the sperm staining kit. Sperm chromatin dispersion (SCD) method was used to detect sperm DNA fragments, and Western-blot was used to detect the protein expression of Trx 2 and TrxR 1.Results: There were no significant differences in sperm density, motility rate, forward motile sperm rate, and DNA fragmentation rate in oligoasthenospermia patients before treatment (P>0.05). However, after 1 month of treatment, the sperm density, motility rate, and forward motile sperm rate were all higher than before treatment (P<0.05), while the DNA fragmentation rate was lower than before treatment. At the same time, each index of semen in the combination group was higher than that in the LC group (P<0.05), and the total effective rate in the combination group was significantly higher than in the LC group (P<0.01). The expression of Trx2 protein in oligoasthenospermia patients was significantly increased (P<0.05), while the expression of TrxR1 protein was significantly decreased (P<0.05). After 3 months of treatment, the expression of Trx2 protein was significantly decreased (P<0.05), while the expression of TrxR1 protein was significantly increased (P<0.05). Conclusions:The results suggest Trx 2 and TrxR 1 may be candidate protein markers for oligoasthenospermia.LC combined with pancreatic kininogenase in the treatment of male oligoasthenospermia can effectively promote sperm maturation, enhance sperm motility, and improve semen quality, which has high application value.

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l-carnitine reduces the adverse effects of ROS and up-regulates the expression of implantation related genes in in vitro developed mouse embryos

Cited by 16 publications

References 36 publications

Mitochondrial Sirtuins in Reproduction

Mitochondrial Sirtuins in Reproduction

Potential utility of l-carnitine for preventing liver tumors derived from metabolic dysfunction–associated steatohepatitis

Effects of L-carnitine combined with pancreatic kininogenase on thioredoxin 2, thioredoxin reductase 1, and sperm quality in patients with oligoasthenospermia

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