Modulation of Carbohydrate Metabolism During N-Methyl N-Nitrosourea Induced Neurotoxicity in Mice: Role of Curcumin

Singla, Neha; Dhawan, D. K.

doi:10.1007/s11064-009-0117-3

Cited by 5 publications

(5 citation statements)

References 51 publications

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“…It is also known that the extra Zn in a cell is associated with MT, suggesting that the increased glycolytic activity is a result of an increase in the pool of freely available Zn in the form of Zn-MT (Frazzini et al, 2006). Zn has been reported as an effective metal in maintaining the level of glucose under different toxic conditions induced by chlorpyrifos and N-methyl-Nnitrosourea (Goel et al, 2006;Singla and Dhawan, 2010). Zn possesses strong antioxidant property and helps cells to maintain normal metabolic functioning (Prasanthi et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Regulatory role of zinc during aluminium‐induced altered carbohydrate metabolism in rat brain

Singla

Dhawan

2011

J of Neuroscience Research

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Aluminium is considered an environmental neurotoxicant and causes many neurological disorders, whereas zinc is vital for many biological functions. The present study was carried out to investigate the role of Zn, if any, in mitigating the adverse effects inflicted by Al on carbohydrate metabolism in rat brain. Male Sprague-Dawley rats weighing 140-160 g were divided into four different groups: normal control, Al-treated (100 mg/kg b.w./day in drinking water via oral gavage), Zn-treated (227mg/liter in drinking water), and combined Al- and Zn-treated rats. All the treatments were continued for 2 months, and their effects on carbohydrate-metabolizing enzymes were studied. Additionally, expressions of the proteins glycogen synthase kinase-3 (GSK3) and protein phosphatase (PP1), which help in regulating carbohydrate energy metabolism, were also studied. Al treatment resulted in increased activities of the glucose-6-phosphatase (G6P), glucose-6-isomerase (G6I), and lactate dehydrogenase (LDH), whereas the activities of hexokinase and succinate dehydrogenase (SDH) and glycogen content were decreased. Moreover, no significant change was observed in the biochemical parameters upon Zn supplementation alone. However, Zn supplementation to Al-treated rats was able to reduce significantly the Al-induced increased activities of G6P, G6I, and LDH, but it elevated the levels of hexokinase, SDH, and glycogen. Furthermore, Al treatment increased the protein expression of GSK3 and decreased the PP1 expression, which were found to be reversed upon Zn administration. Hence, Zn is effective in regulating theAl-induced alterations in carbohydrate metabolism.

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Section: Discussionmentioning

confidence: 99%

Regulatory role of zinc during aluminium‐induced altered carbohydrate metabolism in rat brain

Singla

Dhawan

2011

J of Neuroscience Research

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“…Curcumin administration has been shown to prevent misfiring of neurons following Aβ burden in embryonic hippocampal neurons [140]. In nitrosourea induced neurotoxicity, curcumin administration prevented increase in the activity of glucose metabolic pathway enzymes including hexokinase, LDH and SDH [141]. Similarly, in mercury induced neurotoxicity, pretreatment with curcumin abrogated the increase in metallothinine mRNA and suppressed the toxic and oxidative stress load following mercury exposure in rats [142].…”

Section: Curcumin In Neurodegenerative Diseasementioning

confidence: 99%

Immunomodulatory and therapeutic activity of curcumin

Srivastava

Singh²,

Dubey

et al. 2011

International Immunopharmacology

193

108

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“…DNA adduct formation induces poly (ADP-ribose) polymerase, which results in adenosine triphosphate (ATP) depletion by using nicotinamide adenine dinucleotide for DNA repairment 19 . Additionally, decreased glycogen and increased glycolysis enzymes, such as hexokinase, glucose-6-phosphatase, and glucose-6-isomerase, are induced by MNU in the brains of mice, suggesting complementary glucose metabolism, including glycolysis, to synthesize ATP 31 . Hence, the upregulation of the glycolysis-related genes selectively noted in the LCM samples was considered to be a reactive change against DNA adduct formation in the ONL by MNU treatment.…”

Section: Discussionmentioning

confidence: 99%

Microarray-based gene expression analysis combined with laser capture microdissection is beneficial in investigating the modes of action of ocular toxicity

et al. 2022

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The retina consists of several layers, and drugs can affect the retina and choroid separately. Therefore, investigating the target layers of toxicity can provide useful information pertaining to its modes of action. Herein, we compared gene expression profiles obtained via microarray analyses using samples of target layers collected via laser capture microdissection and samples of the whole globe of the eye of rats treated with N-methyl-N-nitrosourea.Pathway analyses suggested changes in the different pathways between the laser capture microdissection samples and the whole globe samples. Consistent with the histological distribution of glial cells, upregulation of several inflammation-related pathways was noted only in the whole globe samples. Individual gene expression analyses revealed several gene expression changes in the laser capture microdissection samples, such as caspase-and glycolysis-related gene expression changes, which is similar to previous reports regarding N-methyl-N-nitrosourea-treated animals; however, caspase-and glycolysis-related gene expressions did not change or changed unexpectedly in the whole globe samples. Analyses of the laser capture microdissection samples revealed new potential candidate genes involved in the modes of action of N-methyl-N-nitrosourea-induced retinal toxicity. Collectively, our results suggest that specific retinal layers, which may be targeted by specific toxins, are beneficial in identifying genes responsible for drug-induced ocular toxicity.

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Modulation of Carbohydrate Metabolism During N-Methyl N-Nitrosourea Induced Neurotoxicity in Mice: Role of Curcumin

Cited by 5 publications

References 51 publications

Regulatory role of zinc during aluminium‐induced altered carbohydrate metabolism in rat brain

Regulatory role of zinc during aluminium‐induced altered carbohydrate metabolism in rat brain

Immunomodulatory and therapeutic activity of curcumin

Microarray-based gene expression analysis combined with laser capture microdissection is beneficial in investigating the modes of action of ocular toxicity

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