Time course study of oxidative and nitrosative stress and antioxidant enzymes in K₂Cr₂O₇-induced nephrotoxicity

• Main Authors: Saldívar Liliana, Tapia Edilia, Salcedo Marcos I, Maldonado Perla D, Macías-Ruvalcaba Norma A, Hernández-Pando Rogelio, Carvajal Raymundo C, Medina-Campos Omar N, Barrera Diana, Pedraza-Chaverrí José, Castilla María E, Ibarra-Rubio María E
• Format: Article
• Language: English
• Published: BMC 2005-04-01
• Series: BMC Nephrology
• Online Access: http://www.biomedcentral.com/1471-2369/6/4

<p>Abstract</p> <p>Background</p> <p>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).</p> <p>Methods</p> <p>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-β-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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p>