Mitochondrial damage induced by fetal hyperphenylalaninemia in the rat brain and liver: Its prevention by melatonin, Vitamin E, and Vitamin C

Martinez-Cruz, Francisco; Osuna, Carmen; Guerrero, Juan M.

doi:10.1016/j.neulet.2005.02.073

Cited by 35 publications

(18 citation statements)

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“…This model also induced an increase in the formation of lipoperoxidation products (MDA and HNE) in the mitochondria of pup brain and liver (Martínez-Cruz et al 2006). These alterations were totally reversed with the administration of the antioxidants melatonin, vitamin E, and vitamin C to the PKU pregnant rats.…”

Section: Oxidative Stress In Pku: Insights From Animal Studiesmentioning

confidence: 92%

Oxidative Stress in Phenylketonuria: What is the Evidence?

et al. 2011

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Phenylketonuria (PKU) is an inborn error of amino acid metabolism caused by severe deficiency of phenylalanine hydroxylase activity, leading to the accumulation of phenylalanine and its metabolites in blood and tissues of affected patients. Phenylketonuric patients present as the major clinical feature mental retardation, whose pathomechanisms are poorly understood. In recent years, mounting evidence has emerged indicating that oxidative stress is possibly involved in the pathology of PKU. This article addresses some of the recent developments obtained from animal studies and from phenylketonuric patients indicating that oxidative stress may represent an important element in the pathophysiology of PKU. Several studies have shown that enzymatic and non-enzymatic antioxidant defenses are decreased in plasma and erythrocytes of PKU patients, which may be due to an increased free radical generation or secondary to the deprivation of micronutrients which are essential for these defenses. Indeed, markers of lipid, protein, and DNA oxidative damage have been reported in PKU patients, implying that reactive species production is increased in this disorder. A considerable set of data from in vitro and in vivo animal studies have shown that phenylalanine and/or its metabolites elicit reactive species in brain rodent. These findings point to a disruption of pro-oxidant/antioxidant balance in PKU. Considering that the brain is particularly vulnerable to oxidative attack, it is presumed that the administration of appropriate antioxidants as adjuvant agents, in addition to the usual treatment based on restricted diets or supplementation of tetrahydrobiopterin, may represent another step in the prevention of the neurological damage in PKU.

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Section: Oxidative Stress In Pku: Insights From Animal Studiesmentioning

confidence: 92%

Oxidative Stress in Phenylketonuria: What is the Evidence?

et al. 2011

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“…Neurological disorders which have been reported to be improved by administration of melatonin are as follows: Parkinsonism [10], Alzheimer's disease [11], brain edema and traumatic brain injury [12], alcoholism [13], depression [14], cerebral ischemia [15], hyperhomocysteinuria [16], glioma [17] and phenylketonuria [18]. Alzheimer's disease is an age-related progressive neurodegenerative disorder, characterized with loss of cognitive functions, dementia and other neurobiological findings [2,19].…”

Section: öZmentioning

confidence: 99%

A Review of Melatonin, Its Receptors and Drugs

et al. 2016

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After a Turkish scientist took Nobel Prize due to his contributions to understand clock genes, melatonin, closely related to these genes, may begin to shine. Melatonin, a hormone secreted from the pineal gland at night, plays roles in regulating sleep-wake cycle, pubertal development and seasonal adaptation. Melatonin has antinociceptive, antidepressant, anxiolytic, antineophobic, locomotor activityregulating, neuroprotective, anti-inflammatory, pain-modulating, blood pressure-reducing, retinal, vascular, anti-tumor and antioxidant effects. It is related with memory, ovarian physiology, and osteoblast differentiation. Pathologies associated with an increase or decrease in melatonin levels are summarized in the review. Melatonin affects by four mechanisms: 1) Binding to melatonin receptors in plasma membrane, 2) Binding to intracellular proteins such as calmoduline, 3) Binding to Orphan nuclear receptors, and 4) Antioxidant effect. Receptors associated with melatonin are as follows: 1) Melatonin receptor type 1a: MT1 (on cell membrane), 2) Melatonin receptor type 1b: MT2 (on cell membrane), 3) Melatonin receptor type 1c (found in fish, amphibians and birds), 4) Quinone reductase 2 enzyme (MT3 receptor, a detoxification enzyme), 5) RZR/RORα: Retinoid-related Orphan nuclear hormone receptor (with this receptor, melatonin binds to the transcription factors in nucleus), and 6) GPR50: X-linked Melatonin-related Orphan receptor (it is effective in binding of melatonin to MT1). Melatonin agonists such as ramelteon, agomelatine, circadin, TIK-301 and tasimelteon are introduced and side effects will be discussed. In conclusion, melatonin and related drugs is a new and promising era for medicine. Melatonin receptors and melatonin drugs will take attention with greater interest day by day in the future. Keywords: Melatonin, receptors, agonists, pineal gland ÖzSaat genlerini anlamamıza olan katkısından dolayı bir Türk bilim adamı Nobel ödülünü aldıktan sonra, bu genlerle yakın ilişkili olan melatoninin önemi arttı. Melatonin, pineal bezden gece salınan bir hormondur, uyku/uyanıklık döngüsünde, pubertal gelişimde ve mevsimsel adaptasyonda rol alır. Melatoninin antinosiseptif, antidepresan, anksiyolitik, antineofobik, locomotor aktiviteyi düzenleyici, nöroprotektif, antiinflamatuvar, ağrı dü-zenleyici, kan basıncını düşürücü, retinal, vasküler, tümör baskılayıcı ve antioksidan etkileri vardır. Hafıza, over fizyolojisi ve osteoblast diferansiasyonuyla ilişkilidir. Melatonin seviyelerinde artış veya azalışla seyreden patolojiler derlemede özetlenmiştir. Melatonin 4 mekanizmayla etkir: 1) Plazma membranında melatonin reseptörlerine bağlanma, 2) Kalmodulin gibi hücre içi reseptörlere bağlanma, 3) Yetim nükleer reseptörlere bağlanma, 4) Antioksidan etkiler. Melatoninle ilişkili reseptörler şunlardır: 1) Melatonin reseptör tip1a: MT1 (hücre zarında), 2) Melatonin reseptör tip1b: MT2 (hücre zarında), 3) Melatonin reseptör tip1c (balık, amfibiler ve kuşlarda bulunur), 4) Kuinon redüktaz-2 enzimi (MT3 reseptörü, bir detoksifika...

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“…Previous findings suggest that melatonin, both at physiological and pharmacological levels [24,25], functions as an antioxidant and reduces CELLULAR & MOLECULAR BIOLOGY LETTERS 319 oxidative damage in vivo. Melatonin has been tested for its efficacy in reducing biomolecular damage in a large range of experimental conditions where free radicals are believed to be involved [26][27][28][29][30][31]. The beneficial effects of melatonin likely relate to its direct detoxification of free radicals, its indirect antioxidative actions, and its ability to preserve an efficient oxygen metabolism in the mitochondria, and possibly to other activities.…”

Section: Introductionmentioning

confidence: 99%

An autoradiographic study of cellular proliferaton, DNA synthesis and cell cycle variability in the rat liver caused by phenobarbital-induced oxidative stress: The protective role of melatonin

El‐Sokkary¹

2007

Cellular and Molecular Biology Letters

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Abstract:The protective effect of melatonin against phenobarbital-induced oxidative stress in the rat liver was measured based on lipid peroxidation levels (malondialedyde and 4-hydroxyalkenals). Cellular proliferation, DNA synthesis and cell cycle duration were quantitated by the incorporation of 3 H-thymidine, detected by autoradiography, into newly synthesized DNA. Two experiments were carried out in this study, each on four equal-sized groups of male rats (control, melatonin [10 mg/kg], phenobabital [20 mg/kg] and phenobarbital plus melatonin). Experiment I was designed to study the proliferative activity and rate of DNA synthesis, and measure the levels of lipid peroxidation, while experiment II was for cell cycle time determination. Relative to the controls, the phenobarbital-treated rats showed a significant increase (P < 0.01) in the lipid peroxidation levels (30.7%), labelling index (69.4%) and rate of DNA synthesis (37.8%), and a decrease in the cell cycle time. Administering melatonin to the phenobarbital-treated rats significantly reduced (P < 0.01) the lipid peroxidation levels (23.5%), labelling index (38.2%) and rate of DNA synthesis (29.0%), and increased the cell cycle time. These results seem to indicate that the stimulatory effect of phenobarbital on the oxidized lipids, proliferative activity, kinetics of DNA synthesis and cell cycle time alteration in the liver may be one of the mechanisms by which the non-genotoxic mitogen induces its carcinogenic action. Furthermore, melatonin displayed powerful protection against the toxic effect of phenobarbital.

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Mitochondrial damage induced by fetal hyperphenylalaninemia in the rat brain and liver: Its prevention by melatonin, Vitamin E, and Vitamin C

Cited by 35 publications

References 31 publications

Oxidative Stress in Phenylketonuria: What is the Evidence?

Oxidative Stress in Phenylketonuria: What is the Evidence?

A Review of Melatonin, Its Receptors and Drugs

An autoradiographic study of cellular proliferaton, DNA synthesis and cell cycle variability in the rat liver caused by phenobarbital-induced oxidative stress: The protective role of melatonin

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