Padronização da doença renal crônica induzida por cisplatina em modelo experimental in vivo

Abstract

Cisplatin is a widely used antineoplastic in the treatment of several cancers of the ovary, testicles, brain, bladder, lung, breast, and other solid tumors. However, its use is limited in clinical practice because of its potential to cause nephrotoxicity. Chronic kidney disease (CKD) is characterized as an irreversible clinical condition of kidney injury in which the kidney structure or function is persistently impaired. Even when renal function is restored after an acute kidney injury (AKI), these patients are at risk group for CKD, and this requires studies that evaluate the mechanisms involved in the development of CKD and possible therapeutic interventions. The present study aims to standardize a model of CKD induction by cisplatin in female mice. The animals were separated into 4 groups: control (n=8) and cisplatin at doses of 3, 5 and 8 mg/kg (n=10). The animals received 0,9% saline solution intraperitoneally in the case of the control group, and cisplatin at their respective doses once a week for four weeks. At the end of the fourth week, the animals were euthanized to collect blood, urine, and kidney tissue. The proposed lesion model was able to cause significant changes in all the physiological parameters analyzed. Plasma creatinine was increased in the 5 and 8 mg/kg dose, and urea was increased only in the 8 mg/kg dose. Parameters such as creatinine clearance, proteinuria and evaluation of gamma glutamyl transferase (Gamma-GT) enzyme concentration did not show significant differences in relation to the control group. The expression of genes for collagen type 1 alpha 2 (Col1A2), kidney injury molecule-1 (KIM-1) and endothelin production were significantly elevated in all groups, while no increase in tumor nuclear factor alpha (TNF-α) mRNA expression was observed. We conclude that it is necessary to increase the time of injury induction in order to observe the effective establishment of markers related to CKD.