Avaliação do efeito do complexo diclofenaco-zinco sobre a função renal em ratos

Abstract

Diclofenac (DCF) is one of the most commonly prescribed anti-inflammatory medicines in the world due to its analgesic, antipyretic, and anti-inflammatory action. However, gastric irritation is one of the main side effects caused by its use. Aimed at reducing this effect, the zinc-diclofenac (Zn DCF) compound, a deposit patented by CTIT/UFMG, was synthesized. In this light, the present work aims to draw a comparison among the effects of free DCF, DCF associated with zinc acetate (ZnAc), and the Zn DCF complex concerning the renal function of rats with acute tubular necrosis (ATN) induced by gentacimin (GM). To investigate the nephrotoxicity of this medicine, first, the ATN was applied with GM for 5 days in rats maintained individually in metabolic cages, which were later treated for 7 days with the studied compounds. Urine and blood samples were collected after having administered the GM (D0) and on the 4th (D4) and 8th (D8) days after the beginning of treatment. These samples later underwent laboratory analyses. After having finished the treatment, the animals were sacrificed, and the right kidney was removed and sent for morphological analysis. In the ATN caused by GM, one can observe, among other factors, an increase in the plasmatic concentration of creatinine, a reduction in the glomerular filtration, an increase in the urinary flow, an increase in the excretion of water, and an increase in the excretion of Na+ and K+. The GM did not affect parameters such as body weight and ingestion of water, which also showed no changes during treatment with free DCF and DCF associated with ZnAc (3 distinct doses). The DCF compound produced no significant changes in the renal parameters, which had already been altered by GM. In addition, the effects of the Zn DCF, in the majority of analyzed parameters, proved to be no different than those obtained with free DCF or DCF associated with Zn Ac. Nevertheless, in the group treated with the Zn DCF compound, the microalbuminurium was reduced and the renal damage produced by GM was improved. These observations indicate that the Zn DCF compound may well represent a anti-inflammatory medicine of choice in pathological situations where there is a renal dysfunction similar to that investigated in the present study. Another advantage of the Zn DCF compound is that, as it presents a unique pharmaceutical formulation, this may well facilitate and stimulate a better adhesion to the prescribed treatment