title: Mitochondrial activity after cold preservation of pancreatic islet cells treated with pefloxacin (PFX).
abstract: Mitochondrial energetic and oxidative dysfunctions caused by free radical production trigger release of proinflammatory cytokines involved in organ rejection. The aim of this study was to investigate the role of a fluoroquinolone drug, pefloxacin (PFX) and those of various cold preservation solutions on pancreatic beta cell viability. Our data clearly demonstrate that islet cell viability, as determined by glucose-stimulated insulin secretion, is directly correlated with reduced expression of microsomal cytochrome P-450IIIA. Moreover, IL-2, a known mediator of apoptosis was found to be downregulated, whereas TNF-alpha had been upregulated for the first 18 hours after pefloxacin administration. These results demonstrate that pefloxacin downregulates the expression of cytochrome P-450IIIA isozyme and regulates the production of TNF-alpha and IL-2. Thus, we postulate that the presence of pefloxacin in the pancreatic islet cells before organ preservation facilitates increased cell viability.
authors.affiliation: Department of Surgery, College of Physicians and Surgeons of Columbia University, New York, New York, USA.
authors.forename: J
authors.initials: J
authors.lastname: Puc
authors.forename: P
authors.initials: P
authors.lastname: Kwiatkowski
authors.forename: J
authors.initials: J
authors.lastname: Pacanowski
authors.forename: M
authors.initials: M
authors.lastname: Rotbart-Fiedor
authors.forename: A
authors.initials: A
authors.lastname: Wardawa
authors.forename: A P
authors.initials: AP
authors.lastname: Mazurek
authors.forename: W
authors.initials: W
authors.lastname: Rowinski
authors.forename: M A
authors.initials: MA
authors.lastname: Hardy
authors.forename: P
authors.initials: P
authors.lastname: Fiedor
mesh_terms: D042462:4-Quinolones; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases; D002470:Cell Survival / Q000187:drug effects; D003080:Cold Temperature; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D024841:Fluoroquinolones; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007376:Interleukin-2 / Q000235:genetics; D007515:Islets of Langerhans / Q000166:cytology / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000502:physiology; D008861:Microsomes / Q000201:enzymology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D019188:Organ Preservation Solutions; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D011920:Rats, Inbred WF; D014021:Tissue Preservation / Q000379:methods*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015366:Pefloxacin
chemical_list: D042462:4-Quinolones; D000890:Anti-Infective Agents; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System; D024841:Fluoroquinolones; D005947:Glucose; D007328:Insulin; D007376:Interleukin-2; D019188:Organ Preservation Solutions; D010089:Oxidoreductases, N-Demethylating; D015363:Quinolones; D014409:Tumor Necrosis Factor-alpha; D015366:Pefloxacin