title: Prevention of phosphine-induced cytotoxicity by nutrients in HepG2 cells.
abstract: OBJECTIVE
  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 PH3poisoning. 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 PH3cytotoxicity in a cell culture model.
  
  
  METHODS
  PH3was 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 PH3generation 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.
  
  
  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.
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Marzieh
authors.initials: M
authors.lastname: Rashedinia
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy; Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Akram
authors.initials: A
authors.lastname: Jamshidzadeh
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Abbas Rezaiean
authors.initials: AR
authors.lastname: Mehrabadi
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy; Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Niknahad
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004098:Dihydroxyacetone / Q000494:pharmacology; D005632:Fructose / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D056945:Hep G2 Cells / Q000187:drug effects*; D006801:Humans; D007656:Ketoglutaric Acids / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008353:Mannitol / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects; D010720:Phosphines / Q000633:toxicity*
chemical_list: D007656:Ketoglutaric Acids; D010720:Phosphines; D005632:Fructose; D008353:Mannitol; D000255:Adenosine Triphosphate; C044646:phosphine; D005978:Glutathione; D004098:Dihydroxyacetone