title: Influence of analgesic active 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one on the antioxidant status, glucose utilization and lipid accumulation in some in vitro and ex vivo assays.
abstract: OBJECTIVE
  Earlier we demonstrated that 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one (LPP1) elevates nociceptive thresholds in the mouse model of diabetic neuropathic pain. Since drug-induced impairments of glucose and lipid metabolism and the oxidative stress might diminish benefits from analgesia achieved by analgesic drugs used in diabetic neuropathy, the effect of LPP1 on glucose utilization, lipid accumulation and its antioxidant and cytotoxic potential were assessed in some in vitro and ex vivo tests.
  
  
  METHODS
  Total antioxidant capacity was evaluated spectrophotometrically using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical method, whereas the activities of glutathione (GSH) peroxidase and reductase were measured using methods based on the oxidation of NADPH to NADP. The spectrophotometric method for the evaluation of GSH level in mouse brain tissue homogenates involved the oxidation of GSH by the sulfhydryl reagent 5,5'-dithio-bis(2-nitrobenzoic acid) (DTNB) to form a yellow derivative, 5'-thio-2-nitrobenzoic acid (TNB), measurable at 412 nm. Cytotoxicity and glucose utilization were measured in hepatoma HepG2 cells and in 3T3-L1 adipocytes. Lipid accumulation was measured in 3T3-L1 cell lines.
  
  
  RESULTS
  LPP1 had dose-dependent antioxidant properties in DPPH radical assay (14-22% versus control; p < 0.001). Its single administration caused an increase in GSH concentration in brain tissue homogenates of mice by 34% (versus control group; p < 0.05). LPP1 was not cytotoxic and it did not increase glucose utilization or lipid accumulation in cell cultures.
  
  
  CONCLUSIONS
  Previously demonstrated antinociceptive properties of LPP1 are accompanied by a lack of cytotoxicity. LPP1 does not impair glucose or lipid metabolism and is an antioxidant. All these properties might be advantageous for its use in diabetic neuropathy.
authors.affiliation: Department of Pharmacodynamics .
authors.forename: Kinga
authors.initials: K
authors.lastname: Sałat
authors.forename: Monika
authors.initials: M
authors.lastname: Głuch-Lutwin
authors.forename: Barbara
authors.initials: B
authors.lastname: Nawieśniak
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Gawlik
authors.forename: Dorota
authors.initials: D
authors.lastname: Pawlica-Gosiewska
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Witalis
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Kazek
authors.forename: Barbara
authors.initials: B
authors.lastname: Filipek
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Librowski
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Więckowski
authors.forename: Bogdan
authors.initials: B
authors.lastname: Solnica
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D005947:Glucose / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D051379:Mice; D010879:Piperazines / Q000494:pharmacology*; D011758:Pyrroles
chemical_list: C547282:3-(4-(3-trifluoromethylphenyl)piperazin-1-yl)dihydrofuran-2-one; C446974:3-vinylpyrrole; D000700:Analgesics; D000975:Antioxidants; D010879:Piperazines; D011758:Pyrroles; D005978:Glutathione; D005947:Glucose; D015107:4-Butyrolactone