Alterations in apoptotic caspases and antioxidant enzymes in arsenic exposed rat brain regions: Reversal effect of essential metals and a chelating agent

Kadeyala, Praveen Kumar; Sannadi, Saritha; Gottipolu, Rajarami Reddy

doi:10.1016/j.etap.2013.09.021

Cited by 38 publications

(18 citation statements)

References 43 publications

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“…Mood and anxiety are considered as pro-oxidant factors and can contribute to oxidative burden ( Morimoto et al., 2008 ; Tsuboi et al., 2004 ). These findings are in accord with earlier studies that have reported that behavioral abnormality in rats treated with arsenic is linked to enhanced oxidative stress in the brain ( Kadeyala et al., 2013 ; Prakash and Kumar, 2016 ; Prakash et al., 2015 ). The discrepancy in between pro-oxidant and antioxidant ratio leads to the generation of ROS significant oxidative stress.…”

Section: Discussionsupporting

confidence: 93%

Anxiolytic and anti-inflammatory role of thymoquinone in arsenic-induced hippocampal toxicity in Wistar rats

Firdaus

Zafeer

Ahmad

et al. 2018

Heliyon

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Arsenic (As) is a widely existing metalloid in the biosphere. Drinking water contamination by arsenic is a major route of human exposure, either by natural means or through industrial pollution. Numerous evidence form earlier reports suggest that arsenic exposure causes cerebral neurodegeneration which initiates behavioral disturbances concomitant to psychiatric disorders. Also, mood disorders in humans as well as in animals correlate with arsenic exposure; the present study is carried out to implore the neuroprotective potential of thymoquinone (TQ) in arsenic-stressed rats. TQ is an active component of Nigella sativa (Kalonji) seed oil. Arsenic exposure in the form of sodium arsenate (10 mg/kg/day; p.o) caused neurobehavioral deficits as evidenced by changes in locomotion and exploratory behavior in open-field and elevated plus maze tasks. Alongside this, arsenate also elevated hippocampal oxidative stress parameters like lipid peroxidation (TBARS) and protein carbonyl formation with a decrease in superoxide dismutase (SOD) and reduced glutathione (GSH) content. Genotoxicity assessment by Comet assay also showed prominent levels of DNA damage. Furthermore, arsenic also elevated hippocampal cytokine levels, TNF-α and INF-γ. However, TQ supplementation (2.5 and 5 mg/kg/day, p.o) preceded three days before arsenic administration, significantly attenuated arsenic-associated anxiogenic changes which majorly attributed to its antioxidant and anxiolytic potential. Also, TQ pre-treated rats expressed positive shifts in the hippocampal oxidative stress and cytokine levels with decreased DNA fragmentation. Thus, this study concludes that TQ might serve as a strong therapeutic agent for management of anxiety and depressive outcomes of arsenic intoxication.

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Section: Discussionsupporting

confidence: 93%

Anxiolytic and anti-inflammatory role of thymoquinone in arsenic-induced hippocampal toxicity in Wistar rats

Firdaus

Zafeer

Ahmad

et al. 2018

Heliyon

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“…The increase in mitochondrial ROS, lipid peroxidation and reduction in GSH content was also shown by Ghosh et al () in rat brain administrated with sodium arsenite. In a two‐generation study, arsenic exposure to pregnant rats significantly decreased the activities of MnSOD, CAT, GPx, GST and GR with a concomitant increase in lipid peroxidation in the mitochondria of different brain regions of pups (Kadeyala et al ., ; Sannandi et al ., ). Recently, we have also demonstrated increased ROS level, lipid peroxidation and protein oxidation along with decreased MnSOD activity in brain mitochondrion of rats exposed to 25 ppm sodium arsenite for 12 weeks (Prakash et al ., ).…”

Section: Mitochondrial Oxidative Stress In Arsenic Neurotoxicitymentioning

confidence: 98%

“…Ca 2+ , zinc and MiADMSA were co‐administered along with arsenic (100 ppm, in distilled water) from gestational day 6 to postnatal day 18, 21 and 3 months age. Arsenic‐induced mitochondrial oxidative stress was evident by reduced GSH, CAT, SOD, GR and GPx activities and increased lipid peroxidation and GST levels, which could be improved effectively by combined supplementation of Ca 2+ and zinc along with MiADMSA compared to individual administration (Kadeyala et al ., ). Ghosh et al () have demonstrated that combined administration of quercetin and DMSA (capsulated and non‐capsulated) is more effective compared to treatment alone in arsenic‐exposed rats.…”

Section: Amelioration Of Arsenic‐induced Mitochondrial Oxidative Strementioning

confidence: 99%

“…Pachauri et al () have reported reversal of arsenic‐induced altered intracellular Ca +2 level, MMP and monoamine oxidase activity in rat brain by DMSA, MiADMSA and monocyclohexyl DMSA. MiADMSA treatment restored mitochondrial antioxidant enzyme activities such as MnSOD, CAT and GPx with decrease in lipid peroxidation and mRNA expression levels of caspases 3 and 9 in different brain regions of rats treated with sodium arsenite (50 and 100 ppm) from gestational day 6 to postnatal day 18, 21 and 3 months age (Kadeyala et al ., ; Sannadi et al ., ). Another study by Ram Kumar et al () showed that MiADMSA treatment increased activities of antioxidant enzymes MnSOD, CAT, GPx, GR and GST while decreased lipid peroxidation in different brain regions of rats exposed to sodium arsenite.…”

Section: Amelioration Of Arsenic‐induced Mitochondrial Oxidative Strementioning

confidence: 99%

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Mitochondrial oxidative stress and dysfunction in arsenic neurotoxicity: A review

Prakāsh

Soni

Kumar

2015

J of Applied Toxicology

151

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Arsenic is a toxic metalloid present ubiquitously on earth. Since the last decade, it has gained considerable attention due to its severe neurotoxic effects. Arsenic can cross the blood-brain barrier and accumulate in different regions of the brain suggesting its role in neurological diseases. Arsenic exposure has been associated with reactive oxygen species generation, which is supposed to be one of the mechanisms of arsenic-induced oxidative stress. Mitochondria, being the major source of reactive oxygen species generation may present an important target of arsenic toxicity. It is speculated that the proper functioning of the brain depends largely on efficient mitochondrial functions. Multiple studies have reported evidence of brain mitochondrial impairment after arsenic exposure. In this review, we have evaluated the proposed mechanisms of arsenic-induced mitochondrial oxidative stress and dysfunction. The understanding of molecular mechanism of mitochondrial dysfunction may be helpful to develop therapeutic strategies against arsenic-induced neurotoxicity. The ameliorative measures undertaken in arsenic-induced mitochondrial dysfunction have also been highlighted.

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“…Among these monoesters, MiADMSA (monoisoamyl ester of DMSA) has shown a higher efficacy in treating As and Pb poisoning (Flora et al, 2007(Flora et al, , 2008(Flora et al, , 2012Saxena and Flora, 2006). Studies also previously reported that MiADMSA might be a better treatment for Pb-and As-induced alterations in apoptotic pathways and oxidative stress in the developing rat brain (Kadeyala et al, 2013;Saritha et al, 2013). However, it is not known whether this chelating agent, MiADMSA, is equally effective in the recovery of As-and Pb-induced behavioral and neurochemical alterations.…”

Section: Introductionmentioning

confidence: 99%

Effects of combined arsenic and lead exposure on the brain monoaminergic system and behavioral functions in rats: Reversal effect of MiADMSA

et al. 2018

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In this study, we evaluated the therapeutic efficacy of monoisoamyldimercaptosuccinic acid (MiADMSA) against individual and combined effects of arsenic (As) and lead (Pb) on the monoaminergic system and behavioral functions in rats. Pregnant rats were exposed to sodium metaarsenite (50 ppm) and lead acetate (0.2%) individually and in combination (As ¼ 25 ppm þ Pb ¼ 0.1%) via drinking water from gestation day (GD) 6 to postnatal day (PND) 21. MiADMSA (50 mg/kg body weight) was given orally through gavage for 3 consecutive days to pups from PND 18 to PND 20. The results showed increases in synaptosomal epinephrine, dopamine, and norepinephrine levels with individual metal exposures and decreases with combined exposure to As and Pb in the cortex, cerebellum, and hippocampus in PND 21, PND 28, and 3 months age-group rats. We found decreased activity of mitochondrial monoamine oxidase in the selected brain regions following individual and combined exposures to Pb and As. In addition, rats treated with Pb and As alone or in combination showed significant deficits in open-field behavior, grip strength, locomotor activity, and exploratory behavior at PND 28 and 3 months of age. However, MiADMSA administration showed reversal effects against the As-and/or Pbinduced impairments in the monoaminergic system as well as in behavioral functions of rats. Our data demonstrated that the mixture of Pb and As induced synergistic toxicity to developing brain leading to impairments in neurobehavioral functions and also suggest therapeutic efficacy of MiADMSA against Pband/or As-induced developmental neurotoxicity.

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Alterations in apoptotic caspases and antioxidant enzymes in arsenic exposed rat brain regions: Reversal effect of essential metals and a chelating agent

Cited by 38 publications

References 43 publications

Anxiolytic and anti-inflammatory role of thymoquinone in arsenic-induced hippocampal toxicity in Wistar rats

Anxiolytic and anti-inflammatory role of thymoquinone in arsenic-induced hippocampal toxicity in Wistar rats

Mitochondrial oxidative stress and dysfunction in arsenic neurotoxicity: A review

Effects of combined arsenic and lead exposure on the brain monoaminergic system and behavioral functions in rats: Reversal effect of MiADMSA

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