Animal models of gentamicin nephrotoxicity present acute tubular necrosis associated with inflammation, which can contribute to intensify the renal damage. Hydrogen sulfide (H2S) is a signaling molecule involved in inflammation. We evaluated the effect of DL-propargylglycine (PAG), an inhibitor of endogenous H2S formation, on the renal damage induced by gentamicin. Male Wistar rats (N = 8) were injected with 40 mg/kg gentamicin (im) twice a day for 9 days, some of them also received PAG (N = 8, 10 mg·kg−1·day−1, ip). Control rats (N = 6) were treated with saline or PAG only (N = 4). Twenty-four-hour urine samples were collected one day after the end of these treatments, blood samples were collected, the animals were sacrificed, and the kidneys were removed for quantification of H2S formation and histological and immunohistochemical studies. Gentamicin-treated rats presented higher sodium and potassium fractional excretion, increased plasma creatinine [4.06 (3.00; 5.87) mg%] and urea levels, a greater number of macrophages/monocytes, and a higher score for tubular interstitial lesions [3.50 (3.00; 4.00)] in the renal cortex. These changes were associated with increased H2S formation in the kidneys from gentamicin-treated rats (230.60 ± 38.62 µg·mg protein−1·h−1) compared to control (21.12 ± 1.63) and PAG (11.44 ± 3.08). Treatment with PAG reduced this increase (171.60 ± 18.34), the disturbances in plasma creatinine levels [2.20 (1.92; 4.60) mg%], macrophage infiltration, and score for tubular interstitial lesions [2.00 (2.00; 3.00)]. However, PAG did not interfere with the increase in fractional sodium excretion provoked by gentamicin. The protective effect of PAG on gentamicin nephrotoxicity was related, at least in part, to decreased H2S formation.
Fundamento: A doença de Chagas (DC) constitui uma causa potencial negligenciada de doença microvascular coronariana (DMC). Objetivos: Comparar pacientes com DMC relacionada à DC (DMC-DC) com pacientes com DMC ligada a outras etiologias (DMC-OE). Métodos: De 1292 pacientes estáveis, encaminhados para angiografia coronária invasiva para elucidar o padrão hemodinâmico e a causa de angina, 247 apresentaram coronárias subepicárdicas normais, e 101 foram incluídos após aplicação dos critérios de exclusão. Desses, 15 compuseram o grupo de DMC-DC e suas características clínicas, hemodinâmicas, angiográficas, e cintilográficas foram comparadas às do grupo de 86 pacientes com DMC-OE. O nível de significância estatística para todas as comparações adotado foi de 0,05. Resultados: Pacientes com suspeita de DMC-DC apresentaram características antropométricas, clínicas e angiográficas, além de alterações hemodinâmicas e de perfusão miocárdica estatisticamente comparáveis às detectadas nos 86 pacientes com DMC-OE. Disfunção ventricular diastólica, expressa por elevada pressão telediastólica do ventrículo esquerdo, foi igualmente encontrada nos dois grupos. Entretanto, em comparação a esse grupo com DMC-OE, o grupo com DMC-DC exibiu fração de ejeção ventricular esquerda mais baixa (61,
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