Evaluation of nephrotoxicity of single-dose amikacin in diabetic and metabolic memory zebrafish.

• Grant number: 24/14791-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: April 01, 2025
• End date: March 31, 2026
• Field of knowledge: Biological Sciences - Physiology - Compared Physiology
• Principal Investigator: Marisa Narciso Fernandes
• Grantee: Alice Fernanda Aparecida Dias
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

Diabetes is a chronic disease that has been increasing steadily in the population and its main characteristic is hyperglycemia, which triggers several pathophysiological processes in patients, including glucotoxicity in the kidneys and immunosuppression that favors recurrent urinary tract infection (UTIs). Antibiotics are commonly used to treat UTI caused by gram-negative bacteria, including aminoglycosides, which have fallen into disuse due to their nephrotoxic potential, but have been gaining renewed interest due to the increase in bacterial resistance and the single-dose treatment approach. Diabetic patients are more predisposed to UTIs and kidney damage due to hyperglycemia, so it is important to understand whether the use of single-dose aminoglycosides, especially amikacin, is safe for this risk group with glycemic control or decompensated glycemia. Zebrafish (Danio rerio) have proven to be an effective experimental model for biomedical research due to their high degree of endocrine and renal physiological similarity with humans. Its size makes it an efficient experimental model, where it is possible to develop experiments in less time, space in aquariums and inputs used. Thus, this study aims to evaluate the nephrotoxicity of the use of amikacin in a single dose in zebrafish induced with diabetes mellitus (DM) - hyperglycemic (i), with metabolic memory for diabetes (MM) - normoglycemic (ii) and control (C) (iii). For this, streptozocin will be used, which acts by destroying pancreatic beta cells in adult zebrafish (3-5 months) to induce DM and MM and antibiotic therapy with amikacin in a single dose. Subsequently, blood glucose tests will be performed in the three groups to confirm the induction of a glycemic phenotype by streptozocin, and the degree of inflammation in the kidneys of zebrafish will be evaluated by flow cytometry to detect neutrophils, an assay to detect in situ cell death in the kidneys, and histological slides stained with hematoxylin-eosin to analyze nephrotoxicity. This study is expected to evaluate the possible level of inflammation, increased apoptosis, and kidney injury caused by the nephrotoxicity of the use of a single dose of amikacin in the DM, MM, and C models, and to evaluate the cost-benefit and safety of this therapeutic approach for these groups.