title: Time course study of oxidative and nitrosative stress and antioxidant enzymes in K2Cr2O7-induced nephrotoxicity.
abstract: BACKGROUND
  Potassium dichromate (K2Cr2O7)-induced nephrotoxicity is associated with oxidative and nitrosative stress. In this study we investigated the relation between the time course of the oxidative and nitrosative stress with kidney damage and alterations in the following antioxidant enzymes: Cu, Zn superoxide dismutase (Cu, Zn-SOD), Mn-SOD, glutathione peroxidase (GPx), glutathione reductase (GR), and catalase (CAT).
  
  
  METHODS
  Nephrotoxicity was induced in rats by a single injection of K2Cr2O7. Groups of animals were sacrificed on days 1,2,3,4,6,8,10, and 12. Nephrotoxicity was evaluated by histological studies and by measuring creatinine clearance, serum creatinine, blood urea nitrogen (BUN), and urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and total protein. Oxidative and nitrosative stress were measured by immunohistochemical localization of protein carbonyls and 3-nitrotyrosine, respectively. Cu, Zn-SOD, Mn-SOD, and CAT were studied by immunohistochemical localization. The activity of total SOD, CAT, GPx, and GR was also measured as well as serum and kidney content of chromium and urinary excretion of NO2 -/NO3-. Data were compared by two-way analysis of variance followed by a post hoc test.
  
  
  RESULTS
  Serum and kidney chromium content increased reaching the highest value on day 1. Nephrotoxicity was made evident by the decrease in creatinine clearance (days 1-4) and by the increase in serum creatinine (days 1-4), BUN (days 1-6), urinary excretion of NAG (days 1-4), and total protein (day 1-6) and by the structural damage to the proximal tubules (days 1-6). Oxidative and nitrosative stress were clearly evident on days 1-8. Urinary excretion of NO2-/NO3- decreased on days 2-6. Mn-SOD and Cu, Zn-SOD, estimated by immunohistochemistry, and total SOD activity remained unchanged. Activity of GPx decreased on days 3-12 and those of GR and CAT on days 2-10. Similar findings were observed by immunohistochemistry of CAT.
  
  
  CONCLUSIONS
  These data show the association between oxidative and nitrosative stress with functional and structural renal damage induced by K2Cr2O7. Renal antioxidant enzymes were regulated differentially and were not closely associated with oxidative or nitrosative stress or with kidney damage. In addition, the decrease in the urinary excretion of NO2-/NO3- was associated with the renal nitrosative stress suggesting that nitric oxide was derived to the formation of reactive nitrogen species involved in protein nitration.
authors.affiliation: Departamento de Biología, Universidad Nacional Autónoma de México, Facultad de Química, Ciudad Universitaria, 04510, México, D.F., Mexico. pedraza@servidor.unam.mx
authors.forename: José
authors.initials: J
authors.lastname: Pedraza-Chaverrí
authors.forename: Diana
authors.initials: D
authors.lastname: Barrera
authors.forename: Omar N
authors.initials: ON
authors.lastname: Medina-Campos
authors.forename: Raymundo C
authors.initials: RC
authors.lastname: Carvajal
authors.forename: Rogelio
authors.initials: R
authors.lastname: Hernández-Pando
authors.forename: Norma A
authors.initials: NA
authors.lastname: Macías-Ruvalcaba
authors.forename: Perla D
authors.initials: PD
authors.lastname: Maldonado
authors.forename: Marcos I
authors.initials: MI
authors.lastname: Salcedo
authors.forename: Edilia
authors.initials: E
authors.lastname: Tapia
authors.forename: Liliana
authors.initials: L
authors.lastname: Saldívar
authors.forename: María E
authors.initials: ME
authors.lastname: Castilla
authors.forename: María E
authors.initials: ME
authors.lastname: Ibarra-Rubio
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine; D000818:Animals; D002374:Catalase / Q000378:metabolism; D002857:Chromium / Q000097:blood / Q000378:metabolism; D003401:Creatine / Q000097:blood / Q000652:urine; D005979:Glutathione Peroxidase / Q000378:metabolism; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000473:pathology; D008297:Male; D009566:Nitrates / Q000652:urine; D009573:Nitrites / Q000652:urine; D017672:Nitrogen Compounds / Q000378:metabolism*; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000378:metabolism*; D011192:Potassium Dichromate / Q000506:poisoning; D011507:Proteinuria / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D009566:Nitrates; D009573:Nitrites; D017672:Nitrogen Compounds; D002857:Chromium; D010088:Oxidoreductases; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000118:Acetylglucosaminidase; D003401:Creatine; D011192:Potassium Dichromate