Melatonin Prevents Hyperhomocysteinemia and Neural Lipid Peroxidation Induced by Methionine Intake

Bouzouf, Mounir; Martinez-Cruz, Francisco; Molinero, Patrocinio; Guerrero, Juan M.; Osuna, Carmen

doi:10.2174/1567202053586839

Cited by 14 publications

(6 citation statements)

References 12 publications

(16 reference statements)

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“…Methionine is a metabolite that is important for GSH synthesis in the liver ( 55 ). Oral administration of methionine at high doses was reported to markedly elevate the level of homocysteine in rat plasma, while long-term MT administration significantly reduced homocysteine levels ( 56 ). Based on this observation, the close association between methionine and GSH is confirmed.…”

Section: Discussionmentioning

confidence: 99%

Identification of potential biomarkers in cholestasis and the therapeutic effect of melatonin by metabolomics, multivariate data and pathway analyses

et al. 2018

Int J Mol Med

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The present study investigated the anti-cholestatic effect of melatonin (MT) against α-naphthyl isothiocyanate (ANIT)-induced liver injury in rats and screened for potential biomarkers of cholestasis. Rats were administered ANIT by intraperitoneal injection and then sacrificed 36 h later. Serum biochemical parameters were measured and liver tissue samples were subjected to histological analysis. Active components in the serum were identified by gas chromatography-mass spectrometry, while biomarkers and biochemical pathways were identified by multivariate data analysis. The results revealed that the serum levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, γ-glutamyl transpeptidase, and alkaline phosphatase were reduced in rats with ANIT-induced cholestasis that were treated with MT. The histological observations indicated that MT had a protective effect against ANIT-induced hepatic tissue damage. Metabolomics analysis revealed that this effect was likely to be associated with the regulation of compounds related to MT synthesis and catabolism, and amino acid metabolism, including 5-aminopentanoate, 5-methoxytryptamine, L-tryptophan, threonine, glutathione, L-methionine, and indolelactate. In addition, principal component analysis demonstrated that the levels of these metabolites differed significantly between the MT and control groups, providing further evidence that they may be responsible for the effects induced by MT. These results provide an insight into the mechanisms underlying cholestasis development and highlight potential biomarkers for disease diagnosis.

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Section: Discussionmentioning

confidence: 99%

Identification of potential biomarkers in cholestasis and the therapeutic effect of melatonin by metabolomics, multivariate data and pathway analyses

et al. 2018

Int J Mol Med

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“…Ethanol increases the levels of CYP2E1 by a post-transcriptional mechanism, leading to the formation of stable adducts. During its catalytic cycle, CYP2E1, which has high NADPH oxidase activity (Bouzouf et al, 2005), generates ROS and hydrogen peroxide, and in the presence of iron, Fenton reaction takes place, producing more harmful free radicals such as hydroxyl radicals, ferryl species and 1-hydroxyethyl radicals. These ROS damage the cell membranes through lipid peroxidation and the production of lipid aldehydes such as MDA and 4-hydroxynonenal.…”

Section: Mda Levelsmentioning

confidence: 99%

The mechanism of elevated toxicity in HepG2 cells due to combined exposure to ethanol and ionizing radiation

Ogony

Matthews

Anni

et al. 2007

J of Applied Toxicology

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Ethanol and ionizing radiation exposure are independently known to cause tissue damage through various mechanisms. The non-enzymatic and enzymatic metabolism of ethanol, the latter via the cytochrome P(450) 2E1-dependent pathway produces free radicals, which deplete cellular glutathione (GSH). Ionizing radiation exposure has been shown to induce lipid peroxidation, DNA damage, protein oxidation and GSH depletion. It was postulated that cells sensitized by ethanol will be susceptible to additional insult, such as by radiation through increased oxidative stress. In this investigation, cultured liver cells (HepG2, human hepatocellular liver carcinoma) were exposed to ethanol, followed by ionizing radiation. The antioxidant status of the cells was evaluated by an array of techniques. Levels of glutathione, cysteine (CYS), and malondialdehyde (MDA) were measured by HPLC. Activities of antioxidant enzymes, catalase and glutathione reductase (GR) were determined enzymatically. Apoptosis was evaluated by the caspases-3 assay and fluorescence microscopy. The data showed that combined treatment with ethanol and radiation resulted in the lowest levels of GSH, and highest MDA level compared with the control. The catalase activity was lower in the combined exposure groups, when compared with the single agent exposure groups, and the glutathione reductase activity was the highest in the combined exposure groups and lowest in the control. These findings suggest that a combination of ethanol and ionizing radiation results in greater toxicity in vitro through elevated oxidative stress.

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“…(2000) in hypercholesterolemic rats and Baydas et al (2002) in normal rats. Melatonin inhibited also lipid peroxidation in the heart (Ahmed et al, 2005), in the brain of methionine treated rats (Bouzouf et al, 2005) and high doses of melatonin inhibit lipid peroxidation in vitro (Tailleux et al, 2005). Stimulating effect of melatonin on antioxidant enzymes was also reported by Ahmed et al (2005) and Nishida (2005).…”

Section: Discussionmentioning

confidence: 78%

• Improving Effect of Fish Oil, Olive Oil and Melatonin on Induced Hypercholesterolemia in Adult Male Rats.

2007

Assiut Veterinary Medical Journal

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This study aims to evaluate the possible improving effects of fish oil, olive oil and melatonin on the induced hypercholesterolemia in adult male rats. 50 rats were used in this study and were divided into 5 groups 10 rats each. Rats of group 1 were fed on a standard diet and those of group 2 were fed on a standard diet enriched with 1% cholesterol (cholesterol fed group) for 10 weaks. Groups 3-5 were fed as in group 2 then the diet was replaced by standard diet and fish oil in group 3 (fish oil group), standard diet and olive oil in group 4 (olive oil group) and standard diet and melatonin in group 5 (melatonin group) for 2 weeks . Then, blood samples were taken from all animals and the aorta of each animal was obtained after slaughtering and examined histologically to assess the presence of atherosclerosis. Parameters of the lipogram [total plasma cholesterol (TPC), high density lipoprotein (HDL), low density lipoprotein (LDL) and triglycerides (TG)], superoxide dismutase (SOD), total thiol, nitric oxide (NO) and lipid peroxide (LP) were measured.Feeding cholesterol significantly increased TPC, LDL, TG and LP and significantly decreased HDL, SOD, NO and total thiol. There was a significant decrease in TPC, LDL, TG and LP by using fish oil, olive oil and melatonin while, the level of SOD, NO and total thiol were significantly increased and non significant increase in the level of HDL. Fish oil caused the greatest reduction in TG and the greatest increase in NO denoting improvement of vascular endothelial function. Olive oil was the most effective in reducing TPC and total thiol and melatonin was the best factor reducing LDL and LP and consequently atherogenesis and was the most effective in restoring SOD. Histological examination of the aorta from rats of the fish oil , olive oil and melatonin groups showed atheromatous fibrous plaques nearly to the same extent in all groups but absence of well developed fibrous cap which was found in the cholesterol fed group denoting slight improvement. It was concluded that diet additives as fish oil, olive oil or melatonin injection have modulating effect on the parameters of the lipogram, oxidative stress markers and histological features of atherosclerotic lesion and that the improvement of the aortic wall was slight due to the short period of treatment (2 weeks only) to produce marked change in the aortic wall.

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Melatonin Prevents Hyperhomocysteinemia and Neural Lipid Peroxidation Induced by Methionine Intake

Cited by 14 publications

References 12 publications

Identification of potential biomarkers in cholestasis and the therapeutic effect of melatonin by metabolomics, multivariate data and pathway analyses

Identification of potential biomarkers in cholestasis and the therapeutic effect of melatonin by metabolomics, multivariate data and pathway analyses

The mechanism of elevated toxicity in HepG2 cells due to combined exposure to ethanol and ionizing radiation

• Improving Effect of Fish Oil, Olive Oil and Melatonin on Induced Hypercholesterolemia in Adult Male Rats.

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