Perfil epidemiológico e clínico de intoxicações e exposições a agrotóxicos notificadas ao centro de atendimento toxicológico do Espírito Santo (toxcen)

Abstract

Phytotherapy is an important therapeutic option in the prevention and treatment of health problems. Silybum marianum (L.) Gaertn is a plant popularly known as "cardo mariano". From the plant it is possible to obtain silymarin, a complex mixture of flavolignans used in Brazil as a phytotherapeutic medicine as a hepatoprotective, which has silibinin as its major component. Despite having many studies with silymarin, little is known about its effects on the gastric system. Diseases related to the stomach are common conditions that most often lead to chronicity and can progress to cancer. One of the contributing factors for its development is the presence of Helicobacter pylori bacteria. The bacterium can colonize and infect the stomach producing a series of changes that in the long run can culminate in the development of gastric cancer. In this sense, we sought to evaluate the effect of silymarin and silibinin on H. pylori, macrophage imonumodulatory response and cytotoxic activity on gastric tumor cell line. The broth microdilution technique was used to determine the minimum inhibitory concentration (MIC) and then to verify the synergistic activity with metronidazole by the checkerboard method. Evaluation of morphological changes in the bacterial cell was performed by scanning electron microscopy after exposure of the bacteria to sub-MICs. It was also performed the evaluation of the interaction with subunit of PBP by in silico method. Evaluation of urease inhibition was performed in vitro. Immunomodulatory activity was assessed by the detection of nitric oxide and cytokines (TNF-α, IL-6 and IL-10) released by macrophages. Finally, cytotoxic activity in gastric adenocarcinoma cells (AGS) was assessed by the MTT method. Cytotoxicity after metabolization was also evaluated. Silymarin and silibinin showed a discrete activity on H. pylori, showing no synergistic effect with metronidazole. Regarding urease, no significant inhibitory activity was observed. A potential immunomodulatory was observed at 50 μg/mL with inhibition of cytokines produced by H. pylori stimulated macrophages (TNF-ɑ: 84.54 ± 2.24% and 100.00 ± 3.47%, IL-6: 88.66 ± 1.56% and 56.83 ± 6.69%, IL-10: 73.88 ± 3.86% and 70.29 ± 8.41% for silymarin and silibinin respectively) and NO (95.05 ± 7.76% and 73.33 ± 7.14% for silymarin and silibinin). At the same concentration, it presented a mild inhibitory action on superoxide production (35.85 ± 10.98% and 27.09 ± 7.47% for silymarin and silibinin). In addition, they demonstrated significant cytotoxic activity on AGS (IC50: 46.27 ± 1.99 and 55.70 ± 2.14 μg/mL for silymarin and silibinin) with good selectivity index (IS: 2.12 and 1.52 for silymarin and silibinin) when compared to standard chemotherapy. And increased cytotoxicity after metabolization, with decreased IC50. Thus, silymarin and silibinin have been shown to possess important characteristics for potential use in the prevention and treatment of H. pylori infection and its complications, such as gastric cancer.