Renal tight junction proteins are decreased in cisplatin-induced nephrotoxicity in rats
Por:
Trujillo J., Molina-Jijón E., Medina-Campos O.N., Rodríguez-Muñoz R., Reyes J.L., Loredo M.L., Tapia E., Sánchez-Lozada L.G., Barrera-Oviedo D., Pedraza-Chaverri J.
Publicada:
1 oct 2014
Resumen:
Cisplatin (CP) is an antineoplastic agent that induces nephrotoxicity
and oxidative stress. It is unknown whether renal tight junction (TJ)
proteins expression and localization are modified in CP-induced
nephrotoxicity.
Objective: To study if the expression of the TJ proteins occludin,
claudin-2, claudin-5 and zonula occludens-1 (ZO-1) is modified in rats
with CP-induced nephrotoxicity.
Materials and methods: Male Wistar rats (n = 5/group) were injected with
saline solution (V group), and the other group (CP group) was injected
with a single dose of saline solution and CP (7.5 mg/kg i.p.). Rats were
sacrificed 72 h after CP injection and blood, and 24-h urine samples
were collected. Several plasma and urinary injury biomarkers as well as
renal histopathology lesions, oxidative and nitrosative stress markers
were evaluated, and protein levels of ocludin, claudin-2, claudin-5,
ZO-1 were measured by Western blot. Statistically significant changes
noted with different p<0.05 versus V.
Results: Nephrotoxicity was evident by histological alterations,
glycosuria, decrease in creatinine clearance, increase in fractional
excretion of sodium, serum creatinine and kidney injury molecule-1.
These changes were associated with oxidative/nitrosative stress
(increased renal abundance of 3-nitrotyrosine and protein kinase C beta
2 and decreased renal expression of nuclear factor-erythroid-2-related
factor 2) and decreased activity of antioxidant enzymes. Finally, it was
found that CP-induced renal damage was associated with decreased renal
expression of occludin and claudin-2.
Discussion and conclusion: CP altered the TJ proteins expression and
localization in the proximal tubule that was associated with
oxidative/nitrosative stress.
Filiaciones:
Trujillo J.:
Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), Mexico D.F., 04510, Mexico
Molina-Jijón E.:
Department of Physiology, Biophysics and Neuroscience, Center for Research and Advanced Studies, National Polytechnic Institute (Cinvestav-IPN), México D.F., Mexico
Medina-Campos O.N.:
Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), Mexico D.F., 04510, Mexico
Rodríguez-Muñoz R.:
Department of Physiology, Biophysics and Neuroscience, Center for Research and Advanced Studies, National Polytechnic Institute (Cinvestav-IPN), México D.F., Mexico
Reyes J.L.:
Department of Physiology, Biophysics and Neuroscience, Center for Research and Advanced Studies, National Polytechnic Institute (Cinvestav-IPN), México D.F., Mexico
Loredo M.L.:
School of Medicine, Universidad Panamericana, México, D.F., Mexico
Tapia E.:
Laboratory of Renal Pathophysiology, Department of Nephrology, National Institute of Cardiology Ignacio Chávez, México D.F., Mexico
Sánchez-Lozada L.G.:
Laboratory of Renal Pathophysiology, Department of Nephrology, National Institute of Cardiology Ignacio Chávez, México D.F., Mexico
Barrera-Oviedo D.:
Natl Autonomous Univ Mexico UNAM, Fac Med, Dept Pharmacol, Mexico City 04510, DF, Mexico
Department of Pharmacology, Faculty of Medicine, National Autonomous University of Mexico (UNAM), Mexico D.F., Mexico
Pedraza-Chaverri J.:
Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), Mexico D.F., 04510, Mexico
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