Mitochondrial activity after cold preservation of pancreatic islet cells treated with pefloxacin (PFX).
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.
Puc
J
J
Department of Surgery, College of Physicians and Surgeons of Columbia University, New York, New York, USA.
Kwiatkowski
P
P
Pacanowski
J
J
Rotbart-Fiedor
M
M
Wardawa
A
A
Mazurek
A P
AP
Rowinski
W
W
Hardy
M A
MA
Fiedor
P
P
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
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