title: Evaluation of antinociceptive and antioxidant properties of 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one in mice.
abstract: The aim of this study was to evaluate the influence of 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one (LPP1) on nociceptive thresholds in mouse models of persistent pain. Influence of LPP1 on motor coordination and its antioxidant capacity in mouse brain tissue homogenates were also assessed. Pain sensitivity thresholds in animals treated with LPP1 were established using 5 % formalin solution in normoglycemic mice and in streptozotocin (STZ)-treated diabetic mice in the von Frey, hot plate, innocuous, and noxious cold water tests (water at 10 °C and 4 °C, respectively). Motor deficits were assessed in the rotarod test, whereas antioxidant capacities were evaluated using ferric reducing ability of plasma (FRAP) assay, catalase (CAT), and superoxide dismutase (SOD) activities. LPP1was antinociceptive in both phases of the formalin test, in particular, in the late phase (at doses 0.9-30 mg/kg for 66-99 % vs. control normoglycemic mice) and in a statistically significant manner increased nociceptive thresholds in response to mechanical, heat, and noxious cold stimulation in neuropathic mice (at 30 mg/kg for 274, 192, and 316 %, respectively vs. diabetic control). LPP1 did not impair motor coordination of mice in the rotarod revolving at 6 or 18 rpm. In brain tissue homogenates, it demonstrated antioxidant capacity in FRAP assay and increased SOD activity for 63 % (acute administration) and 28 % (chronic administration) vs. control. No influence on CAT activity was observed. LPP1 has significant antinociceptive properties in the formalin model and elevates pain thresholds in neuropathic mice. It has antioxidant capacity and is devoid of negative influence on animals' motor coordination.
authors.affiliation: Department of Pharmacodynamics, Jagiellonian University, Medical College, Medyczna 9, 30-688, Cracow, Poland. salat.kinga@gmail.com
authors.forename: Kinga
authors.initials: K
authors.lastname: Sałat
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Gawlik
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Witalis
authors.forename: Dorota
authors.initials: D
authors.lastname: Pawlica-Gosiewska
authors.forename: Barbara
authors.initials: B
authors.lastname: Filipek
authors.forename: Bogdan
authors.initials: B
authors.lastname: Solnica
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Więckowski
authors.forename: Barbara
authors.initials: B
authors.lastname: Malawska
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003929:Diabetic Neuropathies / Q000188:drug therapy; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D017288:Pain Threshold / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D013311:Streptozocin
chemical_list: C547282:3-(4-(3-trifluoromethylphenyl)piperazin-1-yl)dihydrofuran-2-one; D000700:Analgesics; D000975:Antioxidants; D010879:Piperazines; D013311:Streptozocin; D015107:4-Butyrolactone