Protective effect of new nitrosothiols on the early inflammatory response to kidney ischemia/reperfusion and transplantation in rats.
Renal ischemia/reperfusion (I/R) is characterized by severe inflammatory damage. We assessed the effect of administrating recently developed nitrosothiol compounds acting as nitric oxide (NO) donors on the production of cytokines and other markers of acute inflammatory reaction in an experimental model of warm (I/R), and in a model of cold ischemia and transplant in rats. Warm ischemia was achieved by ligation of left renal pedicle for 60 min, followed by contralateral nephrectomy. NO-donors LA-803, LA-807, LA-810 were administered i.v. (1.8 micromol/kg) during 30 min before reperfusion. Cold ischemia was achieved by preservating the kidney for 24 h in Euro Collins and grafting it in consanguineous Fisher 344/Ico rats. LA-803 was administered in the preservation fluid and in the recipient rat. Reperfusion time was 4 h in warm ischemia and 3 h in cold ischemia + transplantation. Administration of LA-803, LA-807 and, in a lower proportion, LA-810 prevented from the enhanced production of tumor necrosis factor (TNF), interferon-gamma (IFN-gamma), and interleukin-1beta (IL-1beta), the decrease in interleukin-6 (IL-6) and interleukin-10 (IL-10), the increase in tissue level of superoxide anion (SOA) and superoxide dismutase (SOD), and the increase in neutrophil infiltration induced by warm I/R. Treatment with LA-803 in animals with renal transplantation after cold ischemia was also associated with reduced plasma levels of TNF, IFN-gamma, and IL-1beta, increased plasma levels of IL-6 and IL-10, reduced renal levels of SOA and SOD, and reduced neutrophil infiltration. These data demonstrate that systemic administration of new NO-donors with nitrosothiol structure diminished inflammatory responses in a kidney subjected to warm I/R or cold ischemia and transplantation.
García-Criado
F Javier
FJ
Departamento de Cirugía, Facultad de Medicina, Edificio Departamental, Campus Miguel de Unamuno, Universidad de Salamanca, Salamanca, Spain.
Rodriguez-Barca
Pablo
P
García-Cenador
M Begoña
MB
Rivas-Elena
Juan V
JV
Grande
Maria T
MT
Lopez-Marcos
Joaquin F
JF
Mourelle
Marisabel
M
López-Novoa
José M
JM
D000818:Animals; D050377:Cold Ischemia; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood; D005998:Glycine / Q000031:analogs & derivatives; D007113:Immunity, Innate / Q000187:drug effects; D018836:Inflammation Mediators / Q000097:blood; D016030:Kidney Transplantation; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D009603:Nitroso Compounds / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000276:immunology / Q000517:prevention & control*; D026403:S-Nitrosothiols / Q000008:administration & dosage; D013438:Sulfhydryl Compounds / Q000008:administration & dosage*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D052096:Warm Ischemia
D016207:Cytokines; D018836:Inflammation Mediators; C545061:LA 803; C545062:LA 807; C487623:N-(N-gamma-L-glutamyl-2-amino-2-(4-(4-S-nitrosomercapto-1-methylpiperidine)acetyl)glycine); D009603:Nitroso Compounds; D026403:S-Nitrosothiols; D013438:Sulfhydryl Compounds; D013481:Superoxides; D009569:Nitric Oxide; D013482:Superoxide Dismutase; D005998:Glycine