RESUMO
Gram-negative bacterial infections induce inflammation and pain. Lipopolysaccharide (LPS) is a pathogen-associated molecular pattern and the major constituent of Gram-negative bacterial cell walls. Diosmin is a citrus flavonoid with antioxidant and anti-inflammatory activities. Here we investigated the efficacy of diosmin in a nonsterile model of inflammatory pain and peritonitis induced by LPS. Diosmin reduced in a dose-dependent manner LPS-induced inflammatory mechanical hyperalgesia, thermal hyperalgesia, and neutrophil recruitment to the paw (myeloperoxidase activity). Diosmin also normalized changes in paw weight distribution assessed by static weight bearing as a nonreflexive method of pain measurement. Moreover, treatment with diosmin inhibited LPS-induced peritonitis as observed by a reduction of leukocyte recruitment and oxidative stress. Diosmin reduced LPS-induced total ROS production (DCFDA assay) and superoxide anion production (NBT assay and NBT-positive cells). We also observed a reduction of LPS-induced oxidative stress and cytokine production (IL-1ß, TNF-α, and IL-6) in the paw. Furthermore, we demonstrated that diosmin inhibited LPS-induced NF-κB activation in peritoneal exudate. Thus, we demonstrated, using a model of nonsterile inflammation induced by LPS, that diosmin is a promising molecule for the treatment of inflammation and pain.
Assuntos
Anti-Inflamatórios/farmacologia , Hiperalgesia/tratamento farmacológico , Lipopolissacarídeos/farmacologia , NF-kappa B/antagonistas & inibidores , Peritonite/tratamento farmacológico , Animais , Anti-Inflamatórios/química , Antioxidantes/farmacologia , Diosmina/efeitos adversos , Inflamação , Interleucina-1beta , Lipopolissacarídeos/química , Macrófagos/química , Macrófagos/metabolismo , Camundongos , Estrutura Molecular , NF-kappa B/química , Infiltração de Neutrófilos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: Venous ulcers are common complications of chronic venous insufficiency that result in severe physical and mental suffering to patients. The oral administration of diosmin/hesperidin has been used as adjuvant therapy in the treatment of chronic venous insufficiency. The purpose of this study was to evaluate and compare the effect of pycnogenol and diosmin/hesperidin on the healing of venous ulcers. METHODS: This longitudinal, prospective, randomized clinical trial was conducted with 30 adult patients with venous ulcers from a vascular surgery outpatient clinic of a university hospital. The patients were randomly allocated to 2 groups: Group 1 (n = 15) was treated with pycnogenol (50 mg orally, 3 times daily) and Group 2 (n = 15) was treated with diosmin/hesperidin (450/50 mg orally, twice daily). They were assessed every 15 days for 90 days. During follow-up visits, photo-documentation was obtained and the ulcer area and circumference of the affected limb were measured. Friedman's test and Mann-Whitney test were used to compare ulcer areas and circumference of affected limbs between and within groups at different time points. The level of significance was set at 5% (P < 0.05) for all tests. RESULTS: Both the pycnogenol and diosmin/hesperidin treatments had a similar effect on the healing of venous ulcers and led to a significant decrease in the circumference of affected limbs (P < 0.0001). CONCLUSION: The results suggest that pycnogenol has an adjuvant effect on the healing of venous ulcers, similar to diosmin/hesperidin.