RESUMEN
Severe corneal inflammation produces opacity or even perforation, scarring, and angiogenesis, resulting in blindness. In this study, we used the cornea to examine the effect of new anti-angiogenic chemopreventive agents. We researched the anti-angiogenic effect of two extracts, methanol (Met) and hexane (Hex), from the seed of Cucurbita argyrosperma, on inflamed corneas. The corneas of Wistar rats were alkali-injured and treated intragastrically for seven successive days. We evaluated: opacity score, corneal neovascularization (CNV) area, re-epithelialization percentage, and histological changes. Also, we assessed the inflammatory (cyclooxigenase-2, nuclear factor-kappaB, and interleukin-1ß) and angiogenic (vascular endothelial growth factor A, VEGF-A; -receptor 1, VEGFR1; and -receptor 2, VEGFR2) markers. Levels of Cox-2, Il-1ß, and Vegf-a mRNA were also determined. After treatment, we observed a reduction in corneal edema, with lower opacity scores and cell infiltration compared to untreated rats. Treatment also accelerated wound healing and decreased the CNV area. The staining of inflammatory and angiogenic factors was significantly decreased and related to a down-expression of Cox-2, Il-1ß, and Vegf. These results suggest that intake of C. argyrosperma seed has the potential to attenuate the angiogenesis secondary to inflammation in corneal chemical damage.
Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Antiinflamatorios/farmacología , Quemaduras Químicas/tratamiento farmacológico , Córnea/irrigación sanguínea , Córnea/efectos de los fármacos , Neovascularización de la Córnea/tratamiento farmacológico , Cucurbita , Quemaduras Oculares/tratamiento farmacológico , Extractos Vegetales/farmacología , Semillas , Inhibidores de la Angiogénesis/aislamiento & purificación , Proteínas Angiogénicas/metabolismo , Animales , Antiinflamatorios/aislamiento & purificación , Quemaduras Químicas/metabolismo , Quemaduras Químicas/patología , Córnea/metabolismo , Neovascularización de la Córnea/metabolismo , Neovascularización de la Córnea/patología , Opacidad de la Córnea/tratamiento farmacológico , Opacidad de la Córnea/metabolismo , Opacidad de la Córnea/patología , Cucurbita/química , Modelos Animales de Enfermedad , Quemaduras Oculares/metabolismo , Quemaduras Oculares/patología , Mediadores de Inflamación/metabolismo , Masculino , Extractos Vegetales/aislamiento & purificación , Ratas Wistar , Semillas/química , Transducción de Señal/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacosRESUMEN
This observational, open, multicenter clinical trial with a single treatment group aimed to evaluate the effectiveness of a dietary supplement whose main ingredients are hydrolyzed gelatin, chondroitin sulfate, glucosamine sulfate, and devil's claw and bamboo extracts for pain reduction and improvement of functional capacities in patients with osteoarthritis (OA) of the knee and/or hip (REDART study). In all, 130 patients with OA recruited from Spanish hospitals received the dietary supplement for 6 months. The primary outcome was the patients' global assessment of pain in the affected joint as measured with a visual analogue scale (VAS). Other outcome measurements included the Lequesne Functional Index (subindexes for pain/discomfort, distance walked, and daily living) and the Western Ontario and McMaster Universities Arthritis Index (WOMAC; subindexes for pain, stiffness, and physical function). Scores were taken at months 3 and 6 of the treatment. Patients (N = 78) showed a reduction of pain of 3.77 ± 1.77 points after 6 months (p < .0001) in the VAS. The total reduction in the Lequesne Functional Index was 6.30 ± 4.08 points after 6 months (p < .0001), with significant reductions in all subindexes of the scale. A similar pattern was found for the WOMAC index, with an overall reduction of 22.49 ± 14.03 points after 6 months (p < .0001) and significant reductions in all subindexes. No major adverse events were noted during the treatment. This exploratory study shows that treatment with the dietary supplement significantly reduces pain and improves locomotor function in patients with OA of the knee and/or hip.