Oxidant-antioxidant status in Egyptian children with sickle cell anemia: a single center based study / Estado oxidante-antioxidante em crianças egípcias com anemia falciforme: estudo baseado em um único centro

OBJECTIVE: the present study was conducted to investigate the oxidant-antioxidant status in Egyptian children with sickle cell anemia. METHODS: the serum levels of total antioxidant capacity (TAO), paraoxonase (PON), vitamin E, nitrite, and malondialdehyde (MDA) were measured in 40 steady state children with homozygous sickle cell anemia (24 males and 16 females) and 20 apparently healthy age- and gender-matched controls. RESULTS: mean serum TAO, PON, vitamin E, and nitrite levels were significantly lower in the group with sickle cell anemia, whereas mean serum MDA was significantly higher in these children compared to controls. No significant differences in mean levels of TAO, PON, nitrite, vitamin E, and MDA were found in sickle cell anemia patients receiving hydroxyurea when compared with those not receiving hydroxyurea. A significant negative correlation between serum nitrite and the occurrence of vaso-occlusive crises (VOC) was observed (r = -0.3, p = 0.04). PON level was found to be positively correlated with patients' weight and BMI (r = -0.4, p = 0.01; r = -0.7, p < 0.001, respectively), but not with frequency of VOC. The area under the curve of serum nitrite in predicting occurrence of VOC was 0.782, versus 0.701 for PON, and 0.650 for TAO (p = 0.006). Serum MDA was not correlated with nitrite, PON, TAO, or vitamin E levels. No significant correlations were detected between serum nitrite and hemoglobin or antioxidant enzymes. CONCLUSION: children with sickle cell anemia have chronic oxidative stress that may result in increased VOC, and decreased serum nitrite may be associated with increases in VOC frequency. A novel finding in this study is the decrease in PON level in these patients, which is an interesting subject for further research. .

OBJETIVO: o presente estudo foi realizado com o objetivo de investigar o estado oxidante-antioxidante em crianc¸as egípcias com anemia falciforme. MÉTODOS: dosamos os níveis séricos da capacidade antioxidante total (CAT), paraoxonase (PON), vitamina E, nitrito e malondialdeído (MDA) em 40 crianças estáveis com anemia falciforme homozigótica (24 meninos e 16 meninas), e 20 controles pareados por idade/sexo aparente-mente saudáveis. RESULTADOS: os níveis séricos médios da CAT, PON, vitamina E e nitrito foram significativamente menores, ao passo que o nível sérico médio de MDA foi significativamente maior em crianças com anemia falciforme (AF), em comparação aos controles. Não foram encontradasdiferenças significativas nos níveis médios de CAT, PON, nitrito, vitamina E e MDA em pacientescom AF em tratamento com hidroxiureia, em comparação aos que receberam hidroxiureia. Encontramos uma correlação negativa significativa entre o nitrito sérico e a ocorrência decrises vaso-oclusivas agudas (CVO) (r = -0,3, p = 0,04). Descobrimos que o nível de PON está correlacionado positivamente com o peso e o IMC dos pacientes (r = -0,4; p = 0,01; r = -0,7; p < 0,001, respectivamente), porém não com a frequência de CVO. A área sob a curva (ASC) donitrito sérico na previsão da ocorrência de CVO foi 0,782, em comparação a 0,701 para PON e 0,650 para CAT (p = 0,006). O MDA não está correlacionado a nitrito, PON, CAT ou vitamina E. Não foram detectadas correlações significativas entre nitrito sérico e hemoglobina ou enzimas antioxidantes. CONCLUSÃO: crianças com AF apresentam estresse oxidativo crônico que pode resultar emaumento das CVO. Em crianças com AF, a redução nos níveis de ...

Effect of P-glycoprotien blockers on the bioavailability of paclitaxel in swiss albino mice

In this study, we have investigated the influence of P-glycoprotein blockers, namely verapamil and cyclosporine on the oral bioavailability of anticancer paclitaxel, aiming for increasing the oral bioavailability of paclitaxel with possibly reducing its side effect resulting from its parentral administration. The oral bioavailability of paclitaxel [10 mg/kg] in Swiss albino mice pretreated with either verapamil [20 mg/kg] and/or cyclosporine [50 mg/kg] was enhanced by 2.7 and 5.7 fold, respectively. This result may show that both drugs effectively inhibited the P-glycoprotein effhix pump activity in the intestinal tract, allowing for better absorption of paclitaxel. In this context art indirect index of P-glycoprotein efflux activity was used where a certain dye Rh-123 is transported by the membrane efflux P-glycoprotein pump in the same way as paclitaxel. The dye has a certain fluorescence which can be measured spectroflurometrically and its content in the intestinal tissue would reflect the amount absorbed as a result of P-glycoprotein inhibition. This study showed that Rh-123 was alike in the groups of control, i.p., and p.o. of paclitaxel. Pretreatment of oral paclitaxel with either cyclosporine an/or verapamil showed 2 and 1.4 times increase in Rh-123 level, respectively, indicating that cyclosporine was more effective than verapamil in inhibiting P-glycoprotein efflux pump activity. Paclitaxel itself had no effect on the leukocyte count but prior administration of either cyclosporine or verapamil significantly decreased the total number of white blood cells. Cyclosporine seemed to have a greater deleterious effect than verapamil. Both verapamil and cyclosporine given with oral paclitaxel also induced marked rise in the cardiac enzyme CK-MB but the effect was only transient and subsided after 48 hours, this has also been histopathologically confirmed. On the other hand, survival data of Ehrlich carcinoma bearing mice treated with pacliaiel indicated that both P-glycoprotein blockers did not adversely affect the antitumor activity of paclitaxel. Further work would certainly be needed for setting the benefit/risk ratio before the use of Pglycoprotein blockers can be advocated clinically