Impaired mitochondrial energy metabolism and kinetic properties of cytochrome oxidase following acute aluminium phosphide exposure in rat liver

Dua, Raina; Sunkaria, Aditya; Kumar, Vijay; Gill, Kiran Dip

doi:10.1016/j.fct.2009.09.014

Cited by 51 publications

(34 citation statements)

References 34 publications

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“…A direct correlation was also observed between the degree of suppression and mitochondrial respiration; living organisms were not affected when exposed to phosphine under hypoxic conditions (Kashi, 1981) conversely, hyperoxic conditions (Cheng et al, 2003) and mitochondrial uncouplers (Valmas et al, 2008) increased sensitivity. Evidences also show a decrease in mitochondrial oxygen consumption, ATP levels, synthesis and hydrolysis (Dua et al, 2010b) culminating in a metabolic and energy crisis (Dua et al, 2010a;Zuryn et al, 2008). In rat liver AlP has also been shown there is a significant decline in glycolysis (↓activities of hexokinase, phosphofructokinase), increased glycogenolysis (↑glycogen phosphorylase activity) and increased gluconeogenesis (↑glucose-6-phosphatase, ↑fructose-1,6,bisphosphatase activities) (Dua et al, 2010a).…”

Section: Energy Insufficiencymentioning

confidence: 95%

“…Phosphine has been shown to inhibit respiration in insects Price and Dance, 1983), intact nematodes and mitochondria of rat liver (Dua et al, 2010b;Nakakita et al, 1971). A direct correlation was also observed between the degree of suppression and mitochondrial respiration; living organisms were not affected when exposed to phosphine under hypoxic conditions (Kashi, 1981) conversely, hyperoxic conditions (Cheng et al, 2003) and mitochondrial uncouplers (Valmas et al, 2008) increased sensitivity.…”

Section: Energy Insufficiencymentioning

confidence: 96%

“…There is no specific antidote for AlP poisoning and the treatment of AlP poisoning has remained supportive. Scattered evidences are available from the past regarding the mechanism of action of phosphine indicating it interferes with mitochondrial energy production Dua et al, 2010b;Kashi and Chefurka, 1976). The effect has been noted to be specifically with cytochrome a in nematodes however, no such reports are available in rats or humans.…”

Section: Introductionmentioning

confidence: 97%

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Effect of acute aluminum phosphide exposure on rats—A biochemical and histological correlation

et al. 2012

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Section: Energy Insufficiencymentioning

confidence: 95%

Section: Energy Insufficiencymentioning

confidence: 96%

Section: Introductionmentioning

confidence: 97%

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Effect of acute aluminum phosphide exposure on rats—A biochemical and histological correlation

et al. 2012

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“…PH 3 prevents ATP synthesis causing disruption of cell homoeostasis and finally cell death232425. However, oxidative stress and lipid peroxidation and some other mechanisms have also been suggested to be involved in its toxicity and fatality151626.…”

Section: Resultsmentioning

confidence: 99%

Prevention of phosphine-induced cytotoxicity by nutrients in HepG2 cells

Rashedinia

Jamshidzadeh

Mehrabadi

et al. 2016

Indian Journal of Medical Research

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Background & objectives: Phosphides used as an insecticide and rodenticide, produce phosphine (PH3) which causes accidental and intentional poisoning cases and deaths. There is no specific treatment or antidote available for PH3 poisoning. It is suggested that PH3-induced toxicity is associated with adenosine triphosphate (ATP) depletion; therefore, in this study the effect of some nutrients was evaluated on PH3 cytotoxicity in a cell culture model. Methods: PH3 was generated from reaction of zinc phosphide (10 mM) with water in the closed culture medium of HepG2 cells, and cytotoxicity was measured after one and three hours of incubation. ATP, glutathione (GSH) and lipid peroxidation were also assessed at one or three hours post-incubation. ATP suppliers including dihydroxyacetone, glyceraldehyde and fructose were added to the culture medium 10 min before PH3 generation to prevent or reduce phosphine-induced cytotoxicity. Results: Phosphine caused about 30 and 66 per cent cell death at one and three hours of incubation, respectively. ATP content of the cells was depleted to 14.7 per cent of control at one hour of incubation. ATP suppliers were able to prevent cytotoxicity and ATP depletion induced by PH3. Dihydroxyacetone, α-ketoglutarate, fructose and mannitol restored the ATP content of the cells from 14.7 per cent to about 40, 34, 32 and 30 per cent, respectively. Lipid peroxidation and GSH depletion were not significantly induced by zinc phosphide in this study. Interpretation & conclusions: The results supported the hypothesis that phosphine-induced cytotoxicity was due to decrease of ATP levels. ATP suppliers could prevent its toxicity by generating ATP through glycolysis. α-keto compounds such as dihydroxyacetone and α-ketoglutarate may bind to phosphine and restore mitochondrial respiration.

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“…This effect is attributed mainly to respiratory chain complex IV inhibition (cytochrome c oxidase). As a result, mitochondrial inner membrane potential (Cψm) collapses 6 7. It is well known that Cψm drives ATP synthesis and its breakdown is regarded as a proapoptotic factor 8.…”

Section: Discussionmentioning

confidence: 99%

Aluminium phosphide-induced leukopenia

Ntelios¹,

Mandros²,

Potolidis³

et al. 2013

BMJ Case Reports

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SUMMARYAcute intoxication from the pesticide aluminium phosphide is a relatively rare, life-threatening condition in which cardiovascular decompensation is the most feared problem. We report the case of a patient exposed to aluminium phosphide-liberated phosphine gas. It resulted in the development of a gastroenteritis-like syndrome accompanied by severe reduction in white blood cell numbers as an early and prominent manifestation. By affecting important physiological processes such as mitochondrial function and reactive oxygen species homeostasis, phosphine could cause severe toxicity. After presenting the characteristics of certain leucocyte subpopulations we provide the current molecular understanding of the observed leukopenia which in part seems paradoxical. BACKGROUND

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Impaired mitochondrial energy metabolism and kinetic properties of cytochrome oxidase following acute aluminium phosphide exposure in rat liver

Cited by 51 publications

References 34 publications

Effect of acute aluminum phosphide exposure on rats—A biochemical and histological correlation

Effect of acute aluminum phosphide exposure on rats—A biochemical and histological correlation

Prevention of phosphine-induced cytotoxicity by nutrients in HepG2 cells

Aluminium phosphide-induced leukopenia

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