Efeitos do vitanolídeo D na carcinogênese oral induzida por 4-nitroquinolina-1-óxido em ratos Wistar

Abstract

Cancer is one of the leading causes of death worldwide, with oral squamous cell carcinoma (OSCC) being the most common malignant neoplasm in the oral cavity. The treatment of this malignant neoplasm encompasses surgical approaches and adjuvant therapies, however still revealing high recurrence rates. In light of this problem, studies aim to investigate substances that may act more selectively and effectively against tumor cells. One such substance is withanolide D (VD), a steroidal lactone with anti-inflammatory and immunosuppressive pharmacological properties, commonly used in folk medicine. The present study aimed to evaluate the effects of VD isolated from Acnistus arborescens on oral lesions induced by 4-Nitroquinoline-1-Oxide (4-NQO) in rats, investigating its role in oral carcinogenesis. Forty male Wistar rats were used, divided into the following experimental groups: DMSO (DMSO from the 8th week), 4-NQO (4-NQO for 16 weeks), GV (VD from the 8th week), GT8 (4-NQO for 16 weeks + VD from the 8th week), and GT4 (4-NQO for 16 weeks + VD from the 12th week). 4-NQO was administered on the tongues of the animals daily in the 4-NQO, GT8, and GT4 groups, for 16 weeks, whereas VD (5 mg/kg) was administered intraperitoneally twice a week, for the treatment period corresponding to each test group. After 16 weeks, the animals were euthanized, and blood was collected for biochemical assays. The tongue tissues, esophagus, stomach, kidneys, and liver were collected for macroscopic analysis and histological study, classifying the tongue lesions with dysplasia and OSCC, according to WHO (2022), in scores ranging from 0 to 3. Histologically, the tongues of the 4-NQO group presented lesions, including moderate and severe dysplasias, in addition to areas with well-differentiated OSCC. In the groups treated with VD, especially GT8, a significant reduction in lesion severity was observed (p<0.05), with predominance of mild dysplasias and absence of malignant transformation. The epithelial alterations included loss of stratification, pleomorphism, hyperkeratosis, hyperchromatism, and atypical mitoses, with such alterations being less pronounced in animals that received VD earlier. Statistical analysis also confirmed a significant difference in the distribution of histological scores among the groups (p<0.0001), reinforcing the chemopreventive effect of the compound. In the groups treated with VD, a possible cytoprotective effect was observed in the esophagus and stomach, with lower incidence of dysplasias and reduced cell loss. Biochemical and histological analyses indicated low systemic toxicity associated with the compound, with maintenance of body weight and absence of relevant hepatic and renal alterations. Thus, the findings suggested that VD may be a promising compound as a chemoprotective agent in oral carcinogenesis.