Nephrotoxicity induced by polymixin B in renal ischemia and Diabetes mellitus: pre-clinical test

• Grant number: 20/06245-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2020
• End date: November 30, 2021
• Field of knowledge: Health Sciences - Nursing
• Principal Investigator: Cassiane Dezoti da Fonseca
• Grantee: Eduarda Ferreira da Silva
• Host Institution: Escola Paulista de Enfermagem (EPE). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Acute kidney injury (AKI) is characterized by an abrupt reduction in glomerular filtration and an increase in plasma creatinine values to 1.5 to 2 times the baseline value or an increase of 0.3 mg / dl or reduced urinary flow 0.5 ml / kg / h within 6 hours. Objective: To evaluate the effect of treatment with polymyxin B sulfate in models of risk factors for diabetes mellitus and renal ischemia. Methods: 40 male and adult Wistar rats, weighing 250-290g, will be used. The animals will be randomized into the following experimental groups: a) Citrate (n = 5): animals that will receive the citrate buffer (STZ vehicle) at pH 4.2, i.v .; b) SHAM (n = 5): animals that will be used to simulate the surgical procedure, without clamping the renal pedicles; c) Citrate + PMB (n = 5): citrate animals that will receive 2mg / kg intraperitoneal (i.p.) of polymyxin B sulfate once a day, for five days starting on the 23rd day of experimental protocol I; d) SHAM + PMB (n = 5): SHAM animals that will receive 2mg / kg intraperitoneal (i.p) of polymyxin B sulfate once a day, for five days starting on the 3rd day of experimental protocol II; e) Diabetes mellitus (DM) (n = 5): animals that will receive 65 mg / kg of Streptozotocin, iv, diluted in 0.1M of citrate buffer at pH 4.2 on the 1st day of the protocol and will continue to follow up until the 28th day experimental protocol I; f) Ischemia (n = 5): animals that will be used to clamp the renal pedicles for 30 min; g) Diabetes mellitus + polymyxin B sulfate (DM + PMB) (n = 5): DM animals that will receive 2 mg / kg of PMB, ip, once a day, for five days starting on the 23rd day of the experimental protocol I; h) Ischemia + PMB (n = 5): Ischemia animals that received 2mg / kg intraperitoneal (i.p) of polymyxin B sulfate once daily, for five days starting on the 3rd day of experimental protocol II. Physiological parameters such as weight, feed and water intake, blood glucose and kidney weight to animal weight will be evaluated; renal function (creatinine clearance); renal hemodynamics and oxidative profile (urinary peroxides and TBARS, thiols in renal tissue and urinary nitric oxide). The results will be expressed as mean ± standard deviation. The variance between the groups will be analyzed using the One Way ANOVA test, followed by the Newman-Keuls post-test of multiple comparisons of the statistical program Graph-Pad Prism version-3 for Windows®. Values of p <0.05 will be considered significant. Expected results: Based on the data analysis, the present investigation may contribute to elucidate the pathophysiological mechanisms that result from the nephrotoxicity of PMB in models of risk factors for ischemia and DM. And with that, subsidize a safe multiprofessional practice, based on clinical reasoning and decision making that favor recovery and not an outcome for morbidity and mortality.