Zebrafish como modelo experimental potencial para compreensão de inflamação renal aguda após a exposição a anti-inflamatórios não esteroides

Abstract

Acute Kidney Injury (AKI) is a syndrome with a complex pathophysiology, frequently triggered by the indiscriminate use of nephrotoxic medications. Among the most common agents in clinical practice are non-steroidal anti-inflammatory drugs (NSAIDs), such as diclofenac and ibuprofen, which act by inhibiting cyclooxygenase enzymes (COX-1 and COX-2). Although effective in controlling inflammation and pain, the continuous use or high doses of these drugs can compromise renal hemodynamics through the inhibition of vasodilatory prostaglandins, resulting in a reduction of the glomerular filtration rate, oxidative stress, and inflammatory processes in the kidney. In this context, the zebrafish has stood out as a robust biomedical model for toxicology and human disease studies due to its high genetic homology with humans, rapid development, and a functional renal anatomy comparable to that of mammals. Thus, the present study aimed to propose and apply a histopathological scoring system for the evaluation and quantification of renal damage in adult zebrafish subjected to nephrotoxicity protocols induced by diclofenac and ibuprofen. For this purpose, adult animals were exposed to different forms of drug administration, and acute toxicity assays were performed to determine the dose-response relationship, in addition to histological analyses of the animal's kidney. The evaluation of the tissue slides allowed the identification of structural alterations compatible with kidney injury, including glomerular changes, tubular congestion, inflammatory processes, and tissue disorganization, enabling the application of a score classification system. In animals exposed to the highest concentrations of each drug, more intense renal damage alterations were detected. The results suggest that diclofenac and ibuprofen exert detectable nephrotoxic effects in the teleost model, reinforcing the utility of the zebrafish as a sensitive tool for renal toxicity studies. Furthermore, the application of the scoring system proved to be effective in standardizing and quantifying the observed renal lesions, contributing to more objective and reproducible analyses in experimental models.