Effect of cadmium on 24-hour pattern in expression of redox enzyme and clock genes in rat medial basal hypothalamus

Jiménez-Ortega, Vanesa; Cardinali, Daniel P.; Fernández-Mateos, Pilar; Ríos-Lugo, María J.; Scacchi, Pablo; Esquifino, Ana I.

doi:10.1007/s10534-010-9292-6

Cited by 24 publications

(14 citation statements)

References 41 publications

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“…The data are unpublished results from an experiment reported earlier [[14], see this reference for experimental details]. The sequence of primers used for PCR analysis is described elsewhere [15]. …”

Section: Circadian Disorganization After Hyperadipositymentioning

confidence: 99%

Melatonin and the Metabolic Syndrome: Physiopathologic and Therapeutical Implications

et al. 2011

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Metabolic syndrome (MS) patients exhibit sleep/wake disturbances and other circadian abnormalities, and these may be associated with more rapid weight increase and development of diabetes and atherosclerotic disease. On this basis, the successful management of MS may require an ideal drug that besides antagonizing the trigger factors of MS could also correct the disturbed sleep-wake rhythm. Melatonin is an effective chronobiotic agent able to change the phase and amplitude of circadian rhythms. Melatonin has also significant cytoprotective properties preventing a number of MS sequelae in animal models of diabetes and obesity. A small number of controlled trials indicate that melatonin is useful to treat the metabolic and cardiovascular comorbidities of MS. Whether the recently introduced melatonergic agents (ramelteon, agomelatine, tasimelteon) have the potential for treating sleep disorders in MS patients and, more generally, for arresting the progression of disease, merits further investigation.

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Section: Circadian Disorganization After Hyperadipositymentioning

confidence: 99%

Melatonin and the Metabolic Syndrome: Physiopathologic and Therapeutical Implications

et al. 2011

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“…Less information is available on the mediation by redox mechanisms of brain effects of a low concentration of Cd. In a recent study we examined the effect of a low dose of Cd (7.5 μg/day) on 24-h changes in expression of redox pathway enzyme and circadian genes in rat medial basal hypothalamus (MBH; Jiménez-Ortega et al, 2010). In CdCl 2 -treated rats a disruption of 24-h pattern of MBH gene expression of nitric oxide synthase (NOS)-1 and -2, heme oxygenase (HO)-1 and -2, Mn-superoxide dismutase (Mn-SOD), catalase, glutathione peroxidase (GPx), and glutathione reductase (GSR) was detectable.…”

Section: Introductionmentioning

confidence: 99%

“…Mean 24-h levels of MBH mRNA for HO-2, Mn-SOD, and catalase augmented after Cd intake (presumably as a compensatory increase caused by the augmented oxidative load), whereas those of NOS-2 decreased (presumably because Cd causes toxicity independently of NO formation; Wright and Baccarelli, 2007). After CdCl 2 intake, the 24-h pattern of clock gene expression in MBH seen in control rats was significantly disrupted, suggesting that a primary mechanism of action could be on circadian clock mechanisms (Jiménez-Ortega et al, 2010). …”

Section: Introductionmentioning

confidence: 99%

Cadmium-Induced Disruption in 24-h Expression of Clock and Redox Enzyme Genes in Rat Medial Basal Hypothalamus: Prevention by Melatonin

Jiménez-Ortega¹,

Cano-Barquilla²,

Scacchi³

et al. 2011

Front. Neur.

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In a previous study we reported that a low daily p.o. dose of cadmium (Cd) disrupted the circadian expression of clock and redox enzyme genes in rat medial basal hypothalamus (MBH). To assess whether melatonin could counteract Cd activity, male Wistar rats (45 days of age) received CdCl2 (5 ppm) and melatonin (3 μg/mL) or vehicle (0.015% ethanol) in drinking water. Groups of animals receiving melatonin or vehicle alone were also included. After 1 month, MBH mRNA levels were measured by real-time PCR analysis at six time intervals in a 24-h cycle. In control MBH Bmal1 expression peaked at early scotophase, Per1 expression at late afternoon, and Per2 and Cry2 expression at mid-scotophase, whereas neither Clock nor Cry1 expression showed significant 24-h variations. This pattern was significantly disrupted (Clock, Bmal1) or changed in phase (Per1, Per2, Cry2) by CdCl2 while melatonin counteracted the changes brought about by Cd on Per1 expression only. In animals receiving melatonin alone the 24-h pattern of MBH Per2 and Cry2 expression was disrupted. CdCl2 disrupted the 24-h rhythmicity of Cu/Zn- and Mn-superoxide dismutase (SOD), nitric oxide synthase (NOS)-1, NOS-2, heme oxygenase (HO)-1, and HO-2 gene expression, most of the effects being counteracted by melatonin. In particular, the co-administration of melatonin and CdCl2 increased Cu/Zn-SOD gene expression and decreased that of glutathione peroxidase (GPx), glutathione reductase (GSR), and HO-2. In animals receiving melatonin alone, significant increases in mean Cu/Zn and Mn-SOD gene expression, and decreases in that of GPx, GSR, NOS-1, NOS-2, HO-1, and HO-2, were found. The results indicate that the interfering effect of melatonin on the activity of a low dose of CdCl2 on MBH clock and redox enzyme genes is mainly exerted at the level of redox enzyme gene expression.

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“…Even though, previously, some studies show 24 hours variations in the antioxidant enzymes expression and activity in the mammals' brain, 21,22,39 all of them were done in animals maintained under light:dark (LD) conditions; thereafter, none of them was able to report circadian, endogenously driven, rhythms in the hippocampus. Particularly, previous studies from our and Sewerynek's labs demonstrated that, under LD conditions, levels of CAT and GPx expression and activity vary throughout a 24-hour period in the rat and chicken hippocampus, respectively.…”

Section: Discussionmentioning

confidence: 99%

Daily rhythms of catalase and glutathione peroxidase expression and activity are endogenously driven in the hippocampus and are modified by a vitamin A-free diet

Navigatore-Fonzo¹,

Delgado²,

Giménez³

et al. 2013

Nutritional Neuroscience

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Effect of cadmium on 24-hour pattern in expression of redox enzyme and clock genes in rat medial basal hypothalamus

Cited by 24 publications

References 41 publications

Melatonin and the Metabolic Syndrome: Physiopathologic and Therapeutical Implications

Melatonin and the Metabolic Syndrome: Physiopathologic and Therapeutical Implications

Cadmium-Induced Disruption in 24-h Expression of Clock and Redox Enzyme Genes in Rat Medial Basal Hypothalamus: Prevention by Melatonin

Daily rhythms of catalase and glutathione peroxidase expression and activity are endogenously driven in the hippocampus and are modified by a vitamin A-free diet

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