Oxidative damage in mitochondrial fatty acids oxidation disorders patients and the in vitro effect of l-carnitine on DNA damage induced by the accumulated metabolites

Moraes, Maira Silmara de; Guerreiro, Gilian; Sitta, Ângela; Coelho, Daniella de Moura; Manfredini, Vanusa; Wajner, Moaçir; Vargas, Carmen Regla

doi:10.1016/j.abb.2019.108206

Cited by 20 publications

(13 citation statements)

References 33 publications

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“…Prevention of apoptosis via LC has been described in the culture medium of neuronal cells (54). LC increases the function of the DNA-repairing enzyme and other associated repair pathways (55). In this experiment, we proved that the quantity of apoptosis in sperm remarkably augmented in the formalin group in comparison with the normal group.…”

Section: Discussionsupporting

confidence: 55%

L-Carnitine reduces the negative effects of formalin on sperm parameters, chromatin condensation and apoptosis in mice: An experimental study

Ezati

Vardiyan

Talebi

et al. 2020

IJRM

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Background: Formalin is commonly applied as an antiseptic and tissue fixative. It has reactive molecules that lead to its cytotoxic effects. According to recent studies, formalin causes a change in the testicular and sperm structure and L-carnitine (LC) acts as an antioxidant to counteract its effects. Objectives: This study aimed to investigate the protective effects of LC on the parameters, chromatin condensation and apoptosis of mice sperm exposed to formalin. Materials and Methods: In this experimental study, 24 balb/c mice (25-40 gr ,10-12 wk) were divided into three groups (n = 8/each): group I without any injections or gavage; group II, received 10 mg/ kg formalin intraperitoneally (I.P); and group III was exposed to formalin and LC, where a dose of 10 mg/kg formalin was injected I.P daily and LC the dose of 100 mg/kg was kept in a solvent solution. After 31 days, the sperm examination was performed as follows: to evaluate chromatin and DNA quality of the sperm, we applied aniline blue (AB), toluidine blue (TB), chromomycin A3 (CMA3), and terminal transferase-mediated deoxy uridine triphosphate biotin end labeling (TUNEL) tests. Results: Sperm parameters such as count, motility, morphology, and viability displayed a significant decrease in the formalin group. While the data exhibited a considerable augment in sperm parameters in the formalin + LC than the formalin and control groups (p < 0.001), significant differences were detected between groups with respect to TB staining, TUNEL test, CMA3 test and AB staining in the formalin and formalin + LC groups. Conclusion: LC can reduce the negative effects of formalin on sperm parameters, chromatin stability, and percentage of apoptosis in an animal model. Key words: Formalin, L-carnitine, Mice, Sperm chromatin, Apoptosis.

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Section: Discussionsupporting

confidence: 55%

L-Carnitine reduces the negative effects of formalin on sperm parameters, chromatin condensation and apoptosis in mice: An experimental study

Ezati

Vardiyan

Talebi

et al. 2020

IJRM

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“…It is also possible that an additional mechanism of action drove the observed in vivo results beyond inflammation. The L-carnitine’s physiological role is to transport fatty acid through the cellular and mitochondrial membranes leading to their usage as a source of energy by the Krebs cycle in the mitochondria [ 21 ]. This enhanced mitochondrial activity was indicated by a decrease in the lactate levels in the rodent serum [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

“…L-carnitine is an amino-acid-like molecule used mainly as a nutritional supplement for a variety of health benefits [ 18 , 19 , 20 ]. L-carnitine’s basic role is to transport fatty acids to the mitochondrial matrix, making them available for beta-oxidation and energy generation through the Krebs cycle [ 21 ]. It is also a powerful anti-oxidant and anti-inflammatory mediator [ 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

L-Carnitine Tartrate Downregulates the ACE2 Receptor and Limits SARS-CoV-2 Infection

et al. 2021

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for one of the worst pandemics in modern history. Several prevention and treatment strategies have been designed and evaluated in recent months either through the repurposing of existing treatments or the development of new drugs and vaccines. In this study, we show that L-carnitine tartrate supplementation in humans and rodents led to significant decreases of key host dependency factors, notably angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), and Furin, which are responsible for viral attachment, viral spike S-protein cleavage, and priming for viral fusion and entry. Interestingly, pre-treatment of Calu-3, human lung epithelial cells, with L-carnitine tartrate led to a significant and dose-dependent inhibition of the infection by SARS-CoV-2. Infection inhibition coincided with a significant decrease in ACE2 mRNA expression levels. These data suggest that L-carnitine tartrate should be tested with appropriate trials in humans for the possibility to limit SARS-CoV-2 infection.

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“…It could potentially be the case that MitoQ does indeed alter State 4 mitochondrial O 2 ·-/H 2 O 2 dynamics which may not be detectable by measures of oxidative damage to DNA or lipids employed within the current study; especially considering the low levels of basal oxidative damage presented in healthy individuals [ 9 , 82 , 83 ]. This highlights the potential that MitoQ may be predominately applicable in conditions characterised by chronic oxidative stress and/or mitochondrial dysfunction such as chronic kidney disease, cardiovascular disease, chronic obstructive pulmonary disorder, acyl-CoA dehydrogenase deficiency, and neurodegenerative diseases [ [84] , [85] , [86] , [87] ].…”

Section: Discussionmentioning

confidence: 99%

The mitochondria-targeted antioxidant MitoQ, attenuates exercise-induced mitochondrial DNA damage

et al. 2020

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High-intensity exercise damages mitochondrial DNA (mtDNA) in skeletal muscle. Whether MitoQ - a redox active mitochondrial targeted quinone - can reduce exercise-induced mtDNA damage is unknown. In a double-blind, randomized, placebo-controlled design, twenty-four healthy male participants consisting of two groups (placebo; n = 12, MitoQ; n = 12) performed an exercise trial of 4 x 4-min bouts at 90–95% of heart rate max. Participants completed an acute (20 mg MitoQ or placebo 1-h pre-exercise) and chronic (21 days of supplementation) phase. Blood and skeletal muscle were sampled immediately pre- and post-exercise and analysed for nuclear and mtDNA damage, lipid hydroperoxides, lipid soluble antioxidants, and the ascorbyl free radical. Exercise significantly increased nuclear and mtDNA damage across lymphocytes and muscle ( P < 0.05), which was accompanied with changes in lipid hydroperoxides, ascorbyl free radical, and α-tocopherol ( P < 0.05). Acute MitoQ treatment failed to impact any biomarker likely due to insufficient initial bioavailability. However, chronic MitoQ treatment attenuated nuclear ( P < 0.05) and mtDNA damage in lymphocytes and muscle tissue ( P < 0.05). Our work is the first to show a protective effect of chronic MitoQ supplementation on the mitochondrial and nuclear genomes in lymphocytes and human muscle tissue following exercise, which is important for genome stability.

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Oxidative damage in mitochondrial fatty acids oxidation disorders patients and the in vitro effect of l-carnitine on DNA damage induced by the accumulated metabolites

Cited by 20 publications

References 33 publications

L-Carnitine reduces the negative effects of formalin on sperm parameters, chromatin condensation and apoptosis in mice: An experimental study

L-Carnitine reduces the negative effects of formalin on sperm parameters, chromatin condensation and apoptosis in mice: An experimental study

L-Carnitine Tartrate Downregulates the ACE2 Receptor and Limits SARS-CoV-2 Infection

The mitochondria-targeted antioxidant MitoQ, attenuates exercise-induced mitochondrial DNA damage

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