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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.
Toxicol Mech Methods. 2014 Mar; 24(3):204-11.TM

Abstract

PURPOSE

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+Show Affiliations

Department of Pharmacodynamics .No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24392931

Citation

Sałat, Kinga, et al. "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." Toxicology Mechanisms and Methods, vol. 24, no. 3, 2014, pp. 204-11.
Sałat K, Głuch-Lutwin M, Nawieśniak B, et al. 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. Toxicol Mech Methods. 2014;24(3):204-11.
Sałat, K., Głuch-Lutwin, M., Nawieśniak, B., Gawlik, K., Pawlica-Gosiewska, D., Witalis, J., Kazek, G., Filipek, B., Librowski, T., Więckowski, K., & Solnica, B. (2014). 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. Toxicology Mechanisms and Methods, 24(3), 204-11. https://doi.org/10.3109/15376516.2013.879973
Sałat K, et al. 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. Toxicol Mech Methods. 2014;24(3):204-11. PubMed PMID: 24392931.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Sałat,Kinga, AU - Głuch-Lutwin,Monika, AU - Nawieśniak,Barbara, AU - Gawlik,Katarzyna, AU - Pawlica-Gosiewska,Dorota, AU - Witalis,Jadwiga, AU - Kazek,Grzegorz, AU - Filipek,Barbara, AU - Librowski,Tadeusz, AU - Więckowski,Krzysztof, AU - Solnica,Bogdan, Y1 - 2014/01/17/ PY - 2014/1/8/entrez PY - 2014/1/8/pubmed PY - 2014/12/17/medline SP - 204 EP - 11 JF - Toxicology mechanisms and methods JO - Toxicol Mech Methods VL - 24 IS - 3 N2 - PURPOSE: 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. SN - 1537-6524 UR - https://www.unboundmedicine.com/medline/citation/24392931/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_ DB - PRIME DP - Unbound Medicine ER -