Renal tight junction proteins are decreased in cisplatin-induced nephrotoxicity in rats

Abstract

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 Cβ2 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.

• Cisplatin
• claudins
• nitrotyrosine
• occludin
• oxidative stress
• tight junction proteins

Acknowledgements

JT, a PhD student, wishes to thank to Posgrado en Ciencias Biológicas de la Universidad Nacional Autonoma de México. This work was supported by CONACYT and PAPIIT. The authors are grateful to Dr. Ismael Torres and Dr. Enrique Pinzón for the technical support with the experimental animals.