title: Inhibiting inducible nitric oxide synthase with rutin reduces renal ischemia/reperfusion injury.
abstract: BACKGROUND
  Nitric oxide (NO) seems to play an important role during renal ischemia/reperfusion (I/R) injury. We investigated whether rutin inhibits inducible nitric oxide synthase (iNOS) and reduces 3-nitrotyrosine (3-NT) formation in the kidneys of rats during I/R.
  
  
  METHODS
  Wistar albino rats were nephrectomized unilaterally and, 2 weeks later, subjected to 45 minutes of left renal pedicle occlusion followed by 3 hours of reperfusion. We intraperitoneally administered L-N6-(1-iminoethyl)lysine (L-NIL; 3 mg/kg) for 30 minutes or rutin (1 g/kg) for 60 minutes before I/R. After reperfusion, kidney samples were taken for immunohistochemical analysis of iNOS and 3-NT. We measured plasma nitrite/nitrate and cyclic guanosine monophosphate (cGMP) to evaluate NO levels.
  
  
  RESULTS
  Ischemia/reperfusion caused plasma cGMP to increase significantly. Similarly, plasma nitrite/nitrate was elevated in the I/R group compared with the control group. Histochemical staining was positive for iNOS and 3-NT in the I/R group. Pretreatment with L-NIL or rutin significantly mitigated the elevation of plasma cGMP and nitrite/nitrate. These changes in biochemical parameters were also associated with changes in immunohistochemical appearance. Pretreatment with L-NIL or rutin significantly decreased the incidence and severity of iNOS and 3-NT formation in the kidney tissues.
  
  
  CONCLUSIONS
  Our findings suggest that high activity of iNOS causes renal I/R injury, and that rutin exerts protective effects, probably by inhibiting iNOS.
authors.affiliation: The Ministry of Agriculture and Rural Affairs, National Food Reference Laboratory, Yenimahalle, Turkey. aslydogan@hotmail.com
authors.forename: Asli
authors.initials: A
authors.lastname: Korkmaz
authors.forename: Dürdane
authors.initials: D
authors.lastname: Kolankaya
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D006152:Cyclic GMP / Q000097:blood; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D007150:Immunohistochemistry; D007263:Infusions, Parenteral; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009392:Nephrectomy; D009566:Nitrates / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000201:enzymology / Q000378:metabolism* / Q000517:prevention & control*; D012431:Rutin / Q000008:administration & dosage / Q000494:pharmacology*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000187:drug effects / Q000378:metabolism
chemical_list: D015415:Biomarkers; D004791:Enzyme Inhibitors; C090663:N(6)-(1-iminoethyl)lysine; D009566:Nitrates; D009573:Nitrites; D020011:Protective Agents; C002744:3-nitrotyrosine; D014443:Tyrosine; D012431:Rutin; D052247:Nitric Oxide Synthase Type II; D006152:Cyclic GMP; D008239:Lysine