Protective effect of dammarane sapogenins against chemotherapy-induced myelosuppression in mice.

Chemotherapy is the most common way to treat malignancies, but myelosuppression, one of its common side-effects, is a formidable problem. The present study described the protective role of dammarane sapogenins (DS), an active fraction from oriental ginseng, on myelosuppression induced by cyclophosphamide (CP) in mice. DS was orally administered at different dosages (37.5, 75, and 150 mg/kg) for 10 d after CP administration (200 mg/kg intraperitoneally). The results showed that DS increased the number of white blood cells (WBC) on day 3 and day 7 (P < 0.05), such that WBC levels were increased by 105.7 ± 29.5% at 75 mg/kg of DS on day 3 (P < 0.05, compared with the CP group). Similar results were observed in red blood cells and platelets in DS-treated groups. The colony-forming assay demonstrated that the depressed numbers of CFU-GM (colony-forming unit-granulocyte and macrophage), CFU-E (colony-forming unit-erythroid), BFU-E (burst-forming unit-erythroid), CFU-Meg (colony-forming unit-megakaryocyte) and CFU-GEMM (colony-forming unit-granulocyte, -erythrocyte, -monocyte and -megakaryocyte) induced by CP were significantly reversed after DS treatment. Moreover, the ameliorative effect of DS on myelosuppression was also observed in the femur by hematoxylin/eosin staining. In DS-treated groups, ConA-induced splenocyte proliferation was enhanced significantly at all the doses (37.5, 75, 150 mg/kg) on day 3 at the rate of 50.3 ± 8.0%, 77.6 ± 8.5% and 44.5 ± 8.4%, respectively, while lipopolysaccharide-induced proliferation was increased mainly on day 7 (P < 0.01), with an increased rate of 39.8 ± 5.6%, 34.9 ± 6.6% and 38.3 ± 7.3%, respectively. The thymus index was also markedly increased by 70.4% and 36.6% at 75 mg/kg on days 3 and 7, respectively, as compared with the CP group. In summary, DS has a protective function against CP-induced myelosuppression. Its mechanism might be related to stimulating hematopoiesis recovery, as well as enhancing the immunological function.

La suplementación aguda con L-Arginina no previene la hematotoxicidad debida a la quimioterapia neoadyuvanteen pacientes con cáncer de mama / Acute Supplementation of L-Arginine does not prevent the hematotoxicity due to neoadjuvant chemotherapy in patients with breast cancer

Introducción: El cáncer de mama ocupa el primer lugar en morbi-mortalidad por neoplasias en la mujer mexicana. La quimioterapia neoadyuvante es el tratamiento de primera línea para las pacientes con enfermedad localmente avanzada; una de sus principal estoxicidades es la mielosupresión, la cual pueda obligar una demora en el tratamiento o disminución en la dosis. La L-arginina es capaz de prevenir este efecto al mantener un balance de nitrógeno positivo y favorecer la proliferación de células hematopoyéticas Objetivo: Evaluar la eficacia de la suplementación de L-arginina sobre prevención de la toxicidad hemática en pacientes con cáncer de mama con quimioterapia neoadyuvante. Materiales y métodos: Ensayo clínico de asignación aleatoria que administró un suplemento de 30 g de L-arginina en cada ciclo de quimioterapia neoadyuvante. Se determinaron los valores de hemoglobina, hematocrito, leucocitos y linfocitos después de cada aplicación del tratamiento antineoplásico. Se realizaron pruebas ANOVA para evaluar los cambios intragrupales a lo largo del tratamiento y pruebas t-student para muestras independientes para las diferencias intergrupales. Resultados: Se evaluaron 45 pacientes. Todas las pacientes presentaron una disminución significativa en los valores hemáticos en cada ocasión evaluada. No se encontraron diferencias significativas entre grupos. Conclusiones: La suplementación con L-arginina no previene la mielosupresión en pacientes con cáncer de mama localmente avanzado que reciben quimioterapia neoadyuvante. Es necesario realizar más ensayos clínicos que permitan obtener la evidencia para recomendar o no la administración de L-arginina como parte del tratamiento integral del paciente oncológico (AU)

Background: Breast cancer is the first cause of morbid-mortality from neoplasms among Mexican women. Neoadjuvant chemotherapy is the first curse of treatment for patients with locally advances disease; one of its main toxicities is myelo suppression. This can frequently cause the patient to delay her treatment or diminish the dosage. L-arginine can prevent this effect by maintaining a positive nitrogen balance and inducing the proliferation of hematopoietic cells. Objective: To evaluate the efficacy of the supplementation of L-arginine on the prevention of hematologic toxicity in patients with breast cancer undergoing neoadjuvant chemotherapy. response to neoadjuvant chemotherapeutic treatment. Materials and methods: We conducted a randomized clinical trial which administered 30 g of L-argininein each chemotherapy cycle. We determined the values of hemoglobin, hematocrit, leucocytes and lymphocytes after each chemotherapy application. We permormed ANOVA tests in order to evaluate intragrupal changes along the antineoplastic treatment and t-student tests for independent samples for evaluating intergrupal differences. Results: 45 patients were assessed. All of them presented a significant decline in hematologic values eachtime. We did not find significant differences between groups. Conclusions: L-arginine supplementation does not prevent myelosuppression in patients with breast cancer under going neoadjuvant chemotherapy. More clinicaltrials are needs in order to obtain sufficient evidence that allows the recommendation (or not) of L-arginineas part of the integral treatment for the oncology patient (AU)

In vitro and in vivo immunostimulatory activity of Woodfordia fruticosa flowers on non-specific immunity.

CONTEXT: Woodfordia fruticosa Kurz. (Lythraceae), a non-rasayana immunomodulatory Indian medicinal plant, used traditionally as an anthelmintic, in dysentery, leprosy, blood diseases, leucorrhea, and menorrhagia. OBJECTIVE: To investigate the effect of ethanol extract of W. fruticosa flowers on non-specific immune responses in mice. MATERIALS AND METHODS: In vitro immunomodulatory activity of the extract was examined on murine peritoneal macrophage phagocytosis (nitroblue tetrazolium (NBT) dye reduction, lysosomal enzyme activity, nitric oxide and myeloperoxidase) and on proliferation of bone marrow cells by sulforhodamine B (SRB) assay, while the in vivo potential on macrophages and bone marrow cells was evaluated by using carbon clearance test and cyclophosphamide-induced myelosuppression, respectively. RESULTS: Significant increase in the release of myeloperoxidase, nitric oxide lysosomal enzyme and superoxide from macrophages along with significant increase in phagocytic index in carbon clearance test indicate stimulatory activity of the extract on macrophages. The extract also demonstrated 60% increase in bone marrow cell proliferation and offer protection towards cyclophosphamide-induced myelosuppression which represents the stimulation of bone marrow activity. DISCUSSION: Significant increase in mediators released from macrophages and phagocytic index in carbon clearance test suggests the release of cytokines from macrophages and stimulation of reticulo-endothelial system. Proliferation of bone marrow cells indicates the plausible release of colony stimulating factors, which further stimulates the immune system through generation of immune cells. CONCLUSION: The result described here indicates the immunostimulatory activity of ethanol extract of W. fruticosa flowers by stimulating non-specific immune responses, macrophages and bone marrow cells.