Effects of L-arginine in renal protection by means of plasma NGAL measurement: a study in an experimental model of ischemia and reperfusion in rats under inhalation anesthesia

• Grant number: 12/13603-2
• Support Opportunities: Regular Research Grants
• Duration: December 01, 2012 - November 30, 2014
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Norma Sueli Pinheiro Módolo
• Grantee: Norma Sueli Pinheiro Módolo
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

The term acute renal failure (ARF) was first used in 1951 by Homer Smith. The imprecise definitions of renal dysfunction have impeded progress, there are over 35 different definitions. The study group Acute Dialysis Quality Initiative developed a guideline for the management of acute kidney injury and RIFLE classification suggested, when it was proposed to use the term acute kidney injury (AKI) instead of ARF. In it the first three items represent the degree of severity and the latter two are prognostic criteria. Serum creatinine and urine output are used to indicate renal dysfunction, but with a very low rate of change, limiting its use in early diagnosis of AKI. The literature has presented several biomarkers that promise early detection of AKI. Between biomarkers we can cite IL-18, NGAL, KIM-1 and cystatin-C. The expression of NGAL occurs in neutrophils and other epithelial cells including the proximal convoluted tubule and in a recent systematic review authors concluded that NGAL appears to have diagnostic and prognostic value for ARL. In the mechanism of cell damage by ischemia initially occurs ATP depletion leading to a definitive loss of mitochondrial function and preventing ATP regeneration after reperfusion. These changes lead to alterations in the cytoskeleton, increasing intracellular calcium, activation of proteases and phospholipases, interstitial inflammation, changes in adhesion receptors and integrins and formation of reactive oxygen species and changes in metabolism of nitric oxide (NO). L-arginine is the substrate for NOS, and his administration seems to be beneficial in the prevention of ischemia reperfusion, reflecting a possible protective function. There are also controversial reports showing that this molecule is cytotoxic and needs further studies. NO protects the vessel acting as a vasodilator, anti-inflammatory agent, inhibiting neutrophil adherence and sequestration of ROS. However reacts with O2-, which is produced by the system of XO, generating peroxynitrite (ONOO-), a product highly cytotoxic which oxidizes various cellular components, one of those responsible by stress nitric. Previous studies have demonstrated the protective effect of l-arginine and allopurinol in damage to I / R in the intestines of rats. While the non-selective NOS inhibitor L-NAME had an opposite effect. In view of this we believe that the protective effect that l-arginine plays in damage to intestinal I / R injury may also occur in I / R kidney. The overall objective of the research will assess whether the L-arginine exerts a protective effect on kidney cells, using an experimental model of ischemia-reperfusion in rats under ether anesthesia and, specifically, to quantify the effectiveness of L-arginine in protecting renal cell under stress of ischemia / reperfusion for histologic analysis and measurement of plasma NGAL. After approval by the Ethics Committee on Animal Experimentation, Faculty of Medicine of Botucatu, will be included in the study, 40 Wistar rats, weighing greater than 250 g, supplied by Central Animal Laboratory of the Botucatu campus, allocated to four groups: Group S (Sham) (n = 10) (laparotomy + right nephrectomy). Group C (Control) (n = 10) (laparotomy + right nephrectomy + L-arginine at dose of 800mg.kg-1.d-1). Group A (n = 10) (laparotomy + right nephrectomy + L-arginine at dose of 800mg.kg-1.d-1 + maneuvers kidney ischemia and reperfusion left. Group I (n = 10) (laparotomy + right nephrectomy + maneuvers of ischemia and reperfusion of the left kidney). All animals will be anesthetized in the same way: induction of anesthesia with isoflurane 3% and maintained with isoflurane in the inspired concentration of 1.5 to 2% and 40% oxygen. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ARANTES, V. M.; BUENO, R. T.; MODOLO, R. P.; DOMINGUES, M. A. C.; DE CARVALHO, L. R.; DO NASCIMENTO JUNIOR, P.; MODOLO, N. S. P.. Effects of Ischemic Preconditioning and Postconditioning in a Renal Ischemia-Reperfusion Injury Model: A Comparative Experimental Study in Rats. Transplantation Proceedings, v. 50, n. 10, p. 3811-3815, DEC 2018. (12/13603-2)