Efeito da Naringina na inflamação e no estresse oxidativo na doença de Crohn experimental induzida por ácido acético em camundongos

Abstract

Inflammatory bowel diseases (IBD) represent a group of chronic idiopathic inflammatory intestinal disorders. The etiology of these diseases is not fully understood, but there is a relationship with genetic, environmental factors, and alterations in the intestinal microbiota. However, the two main categories of IBD are Crohn's disease (CD) and ulcerative colitis (UC), which have overlapping clinical and pathological features and some distinct characteristics. CD can affect the entire gastrointestinal tract and exhibits transmural infiltration and elevated levels of tumor necrosis factor-alpha (TNF-α). It affects the layers surrounding the hollow organs of the intestinal digestive tube, affecting the terminal ileum, cecum, colon, and perianal region, often resulting in granulomas and the development of fistulas. IBDs are incurable, and treatments aim only to control symptoms. Alterations in intestinal mucosal permeability are biological and physiological complications caused by CD. The epithelial cells that form the barrier between the body and the intraluminal microenvironment are highly selective. However, during inflammation, macromolecules such as bacterial or fecal antigens may flow in quantities above normal. The Ministry of Health, through the National Policy of Integrative and Complementary Practices (NPICP), encourages the provision of Acupuncture, Homeopathy, Phytotherapy, Hydrotherapy, and Anthroposophic Medicine in the Unified Health System (SUS). Seeking the development of new strategies and therapeutic agents is essential for the treatment of both pathologies. Naringin is a chemical phytotherapeutic compound that belongs to flavones, known as 4, 5, 7-trihydroxy-flavanone-7-rhamnoglucoside. It was discovered by De Vry in 1857 in Citrus paradisi (Grapefruit) flowers. Naringin presents pharmacological properties such as anti-osteoporotic, anticancer, antiapoptotic, and anti-inflammatory activities, as well as acting on metabolic syndrome and central nervous system disorders, including neurological disorders. It is a substance with great pharmacological potential. In this study, we induced CD in animals. The animals were previously anesthetized intraperitoneally (i.p) with ketamine (60mg/kg) and xylazine (5mg/kg) and challenged with acetic acid (10mg/animal) for three consecutive days. Additional groups received acetic acid (10mg/animal) plus naringin at concentrations of 200 mg/kg, 100 mg/kg, and 50 mg/kg. After the induction protocol of CD by acetic acid, the animals were euthanized 6 hours after the last application. Colon segments of mice were collected for the analysis of the following parameters: macroscopy, microscopy, GSH, MDA, TNF-α, and IL-6. Naringin extract significantly reduced acetic acidinduced macroscopic and microscopic lesions. Naringin at a concentration of 100 mg/kg prevented GSH depletion, reduced MDA levels, and decreased neutrophil infiltration. Furthermore, naringin reduced levels of pro-inflammatory cytokines TNF-α and IL-1β, reversing the effect of acetic acid. Therefore, naringin demonstrated an anti-inflammatory and antioxidant effect in the Crohn's disease model.