Lima-da-Silva Emanuelly Camilly Soares de, Melo Wallacy Watson Pereira, Mendes Paulo Fernando Santos, Pereira Cristian Dos Santos, Matos-Sousa José Mario, Chagas Cristian Kallahan Silva, Morais Hannah Gil de Farias, Freitas Roseana de Almeida, Chaves-Neto Antonio Hernandes, Lima Rafael Rodrigues
Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil.
Department of Oral Pathology, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
PLoS One. 2025 Jun 3;20(6):e0317876. doi: 10.1371/journal.pone.0317876. eCollection 2025.
This study aimed to evaluate the possible biochemical effects of the administration of benznidazole on the parotid and submandibular salivary glands and saliva of rats, as well as on salivary components for the first time. Male Wistar rats (Rattus norvegicus), 66-days-old, weighing approximately 250 g were randomized into two groups: control, administered distilled water by gavage and benznidazole, administered benznidazole at a dose of 19.6 mg/kg daily by gavage over 15 days. On the 16th day, the animals were anaesthetized and the parotid and submandibular salivary glands and saliva were collected for oxidative biochemistry and morphometric analyses, and the biochemical composition of the saliva was also assessed. On the 16th day, the animals were anesthetized and their pilocarpine-induced saliva was collected. They were then euthanized to collect the parotid and submandibular salivary glands for oxidative biochemical and morphometric analyses, and the biochemical composition of the saliva was also assessed. Shapiro-Wilk normality analysis and Student's t-test was used for parametric data and non-parametric data, respectively, with a significance of p < 0.05. The oxidative biochemical results revealed a reduction in the antioxidant capacity of the parotid and submandibular glands in benznidazole group. Morphometric analyses revealed an increase in the average area of the acini in both glands and a reduction in the stromal area of the parotid gland in the benznidazole group. Salivary analyses demonstrated a decrease in antioxidant levels and an increase in pro-oxidant levels in the group exposed to benznidazole. Total proteins, amylase, and mucin levels reduced in the exposed group. Thus, administration of benznidazole conclusively caused biochemical alterations in the antioxidant and morphological capacities of the salivary glands, followed by biochemical and protein alterations in the saliva, highlighting the possible damage caused by the drug in patients during the treatment of Chagas disease.
本研究旨在首次评估给予苯硝唑对大鼠腮腺和颌下唾液腺、唾液以及唾液成分可能产生的生化影响。66日龄、体重约250克的雄性Wistar大鼠（褐家鼠）被随机分为两组：对照组，通过灌胃给予蒸馏水；苯硝唑组，在15天内每天通过灌胃给予剂量为19.6毫克/千克的苯硝唑。在第16天，将动物麻醉，收集腮腺和颌下唾液腺及唾液用于氧化生物化学和形态计量学分析，并评估唾液的生化组成。在第16天，将动物麻醉并收集其毛果芸香碱诱导的唾液。然后对它们实施安乐死以收集腮腺和颌下唾液腺用于氧化生物化学和形态计量学分析，同时也评估唾液的生化组成。分别使用Shapiro-Wilk正态性分析和学生t检验处理参数数据和非参数数据，显著性水平为p < 0.05。氧化生物化学结果显示，苯硝唑组腮腺和颌下腺的抗氧化能力降低。形态计量学分析显示，苯硝唑组两个腺体的腺泡平均面积增加，腮腺的间质面积减少。唾液分析表明，接触苯硝唑的组中抗氧化剂水平降低，促氧化剂水平升高。暴露组的总蛋白、淀粉酶和粘蛋白水平降低。因此，给予苯硝唑最终导致唾液腺的抗氧化和形态学能力发生生化改变，随后唾液出现生化和蛋白质改变，突出了该药物在恰加斯病治疗期间可能对患者造成的损害。
