The role of antiepileptic drugs in free radicals generation and antioxidant levels in epileptic patients.

Many risk factors are encountered during the pathogenesis of epilepsy. In this study, the effect of seizure frequency on free radical generation and antioxidants levels in epileptic patients was evaluated. This study was carried out on 15 healthy controls (GI) and 60 epileptic patients treated with mono- or poly-therapy of carbamazepine, valproic acid, or phenytoin. The treated epileptic patients were divided into 2 main groups according to the seizure frequency: controlled seizure patients GII (n = 30) and uncontrolled seizure patients GIII (n = 30). GII included the GIIA subgroup (n = 15) which had been seizure free for more than 12 months and the GIIB subgroup (n = 15) which had been seizure free for a period from 6 to12 months. GIII included GIIIA (n = 15) and GIIIB (n = 15) for patients which had a seizure frequency of less than and more than four times/month, respectively. In comparison to the control group (GI), the levels of nitric oxide (NO) and malondialdehyde/creatinine ratio were significantly increased in GIIB, GIIIA, and GIIIB, while vitamins A and E levels were significantly decreased in GIIIB. Serum NO levels had significant negative correlations with serum vitamin E in the GIIA and GIIB groups, and with vitamin A in the GIIIA and GIIIB groups. However, serum NO had positive correlation with urinary MDA/Cr ratio. The imbalance between free radical generation and antioxidant system in epileptic patients may be a factor in seizure frequency.

Evaluation of neonatal jaundice in the Makkah region.

The aims of this study were to detect the frequency at which the different types of neonatal jaundice occur in Makkah and to estimate the malondialdehyde (MDA) levels. This study included 239 neonates with neonatal jaundice, 20 anemic neonates and 21 healthy neonates. ABO incompatibility was observed in 31.6% of neonates with indirect hyperbilirubinemia, in 14.3% of those with early onset jaundice, in 9.5% of those with persistent jaundice, in 8.5% of those with physiological jaundice, in 5% of anemic neonates and in 12% of all neonates. glucose-6-phosphate dehydrogenase (G6PD) deficiency was observed in 10.5% of neonates with indirect hyperbilirubinemia, in 3.9% of those with physiological jaundice, in 11.1% of those with direct hyperbilirubinemia, in 12% of those with persistent jaundice, in 10% of anemic neonates and in 6.6% of all neonates. Rh incompatibility and polycythemia were found in 2.6% of neonates with indirect hyperbilirubinemia and in 0.4% of all neonates. In comparison to control group, MDA was significantly higher in all groups except for the anemic group. In conclusion, ABO incompatibility and G6PD deficiency frequently result in neonatal jaundice in Makkah, whereas Rh incompatibility and polycythemia are rare. The MDA level may serve as an indicator of oxidative stress.

Influence of combinations of digitonin with selected phenolics, terpenoids, and alkaloids on the expression and activity of P-glycoprotein in leukaemia and colon cancer cells.

P-glycoprotein (P-gp or MDR1) is an ATP-binding cassette (ABC) transporter. It is involved in the efflux of several anticancer drugs, which leads to chemotherapy failure and multidrug resistance (MDR) in cancer cells. Representative secondary metabolites (SM) including phenolics (EGCG and thymol), terpenoids (menthol, aromadendrene, ß-sitosterol-O-glucoside, and ß-carotene), and alkaloids (glaucine, harmine, and sanguinarine) were evaluated as potential P-gp inhibitors (transporter activity and expression level) in P-gp expressing Caco-2 and CEM/ADR5000 cancer cell lines. Selected SM increased the accumulation of the rhodamine 123 (Rho123) and calcein-AM (CAM) in a dose dependent manner in Caco-2 cells, indicating that they act as competitive inhibitors of P-gp. Non-toxic concentrations of ß-carotene (40µM) and sanguinarine (1µM) significantly inhibited Rho123 and CAM efflux in CEM/ADR5000 cells by 222.42% and 259.25% and by 244.02% and 290.16%, respectively relative to verapamil (100%). Combination of the saponin digitonin (5µM), which also inhibits P-gp, with SM significantly enhanced the inhibition of P-gp activity. The results were correlated with the data obtained from a quantitative analysis of MDR1 expression. Both compounds significantly decreased mRNA levels of the MDR1 gene to 48% (p<0.01) and 46% (p<0.01) in Caco-2, and to 61% (p<0.05) and 1% (p<0.001) in CEM/ADR5000 cells, respectively as compared to the untreated control (100%). Combinations of digitonin with SM resulted in a significant down-regulation of MDR1. Our findings provide evidence that the selected SM interfere directly and/or indirectly with P-gp function. Combinations of different P-gp substrates, such as digitonin alone and together with the set of SM, can mediate MDR reversal in cancer cells.