Manganese-Induced Neurotoxicity is Differentially Enhanced by Glutathione Depletion in Astrocytoma and Neuroblastoma Cells

Dukhande, Vikas V.; Malthankar‐Phatak, Gauri H.; Hugus, Jeremy J.; Daniels, Christopher K.; Lai, James C. K.

doi:10.1007/s11064-006-9179-7

Cited by 61 publications

(39 citation statements)

References 36 publications

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“…An imbalance between ROS generation and the antioxidant defense mechanisms with subsequent oxidative stress (Betteridge 2000) can initiate apoptosis and/or necrosis in several tissues (Orrenius et al 2007). Oxidative stress is in fact one of the putative mechanisms by which Mn induces neuronal damages (Dukhande et al 2006). Efforts have been made to minimize the severity of manganese toxicity via its enhanced sequestration and elimination using different agents.…”

Section: Introductionmentioning

confidence: 99%

Silymarin, a natural antioxidant, protects cerebral cortex against manganese-induced neurotoxicity in adult rats

et al. 2010

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Manganese (Mn) is an essential element for biological systems, nevertheless occupational exposure to high levels of Mn can lead to neurodegenerative disorders, characterized by serious oxidative and neurotoxic effects with similarities to Parkinson's disease. The aim of this study was to investigate the potential effects of silymarin (SIL), an antioxidant flavonoid, against manganese chloride induced neurotoxicity both in vivo (cerebral cortex of rats) and in vitro (Neuro2a cells). Twenty-eight male Wistar rats were randomly divided into four groups: the first group (C) received vehicle solution (i.p.) served as controls. The second group (Mn) received orally manganese chloride (20 mg/ml). The third group (Mn + SIL) received both Mn and SIL. The fourth group (SIL) received only SIL (100 mg/kg/day, i.p.). Animals exposed to Manganese chloride showed a significant increase in TBARS, NO, AOPP and PCO levels in cerebral cortex. These changes were accompanied by a decrease of enzymatic (SOD, CAT, GPx) and non-enzymatic (GSH, NpSH, Vit C) antioxidants. Co-administration of silymarin to Mn-treated rats significantly improved antioxidant enzyme activities and attenuated oxidative damages observed in brain tissue. The potential effect of SIL to prevent Mn induced neurotoxicity was also reflected by the microscopic study, indicative of its neuroprotective effects. We concluded that silymarin possesses neuroprotective potential, thus validating its use in alleviating manganese-induced neurodegenerative effects.

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Section: Introductionmentioning

confidence: 99%

Silymarin, a natural antioxidant, protects cerebral cortex against manganese-induced neurotoxicity in adult rats

et al. 2010

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“…Moreover, astrocytes protect neurons against various pathophysiological assaults (e.g., oxidative stress, ammonia toxicity) (Dukhande et al, 2006;Wong et al, 2010). However, to what extent these physiological roles are still assumed by astrocytes once they are transformed into astrocytomas has not been elucidated.…”

Section: Metabolism Metabolic and Other Functional Roles Of Astrocytementioning

confidence: 99%

Glioblastoma: Current Chemotherapeutic Status and Need for New Targets and Approaches

Jain¹,

Lai²,

Chowdhury³

et al. 2011

Brain Tumors - Current and Emerging Therapeutic Strategies

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“…Likewise, loss of PrP C function due to conversion to the PrP Sc form may account for the increase in protein damage and markers of oxidative stress observed in sCJD and scrapie-infected mouse brains (64,245). Continued oxidative stress is likely to deplete glutathione, a potent free-radical scavenger in the brain, thus intensifying toxicity (57).…”

Section: Prpmentioning

confidence: 99%

Redox Control of Prion and Disease Pathogenesis

Singh

Das

et al. 2010

Antioxidants & Redox Signaling

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Imbalance of brain metal homeostasis and associated oxidative stress by redox-active metals like iron and copper is an important trigger of neurotoxicity in several neurodegenerative conditions, including prion disorders. Whereas some reports attribute this to end-stage disease, others provide evidence for specific mechanisms leading to brain metal dyshomeostasis during disease progression. In prion disorders, imbalance of brain-iron homeostasis is observed before end-stage disease and worsens with disease progression, implicating ironinduced oxidative stress in disease pathogenesis. This is an unexpected observation, because the underlying cause of brain pathology in all prion disorders is PrP-scrapie (PrP Sc ), a b-sheet-rich conformation of a normal glycoprotein, the prion protein (PrP C ). Whether brain-iron dyshomeostasis occurs because of gain of toxic function by PrP Sc or loss of normal function of PrP C remains unclear. In this review, we summarize available evidence suggesting the involvement of oxidative stress in prion-disease pathogenesis. Subsequently, we review the biology of PrP C to highlight its possible role in maintaining brain metal homeostasis during health and the contribution of PrP Sc in inducing brain metal imbalance with disease progression. Finally, we discuss possible therapeutic avenues directed at restoring brain metal homeostasis and alleviating metal-induced oxidative stress in prion disorders. Antioxid. Redox Signal. 12, 1271-1294.

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Manganese-Induced Neurotoxicity is Differentially Enhanced by Glutathione Depletion in Astrocytoma and Neuroblastoma Cells

Cited by 61 publications

References 36 publications

Silymarin, a natural antioxidant, protects cerebral cortex against manganese-induced neurotoxicity in adult rats

Silymarin, a natural antioxidant, protects cerebral cortex against manganese-induced neurotoxicity in adult rats

Glioblastoma: Current Chemotherapeutic Status and Need for New Targets and Approaches

Redox Control of Prion and Disease Pathogenesis

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