Restoration of pro-inflammatory cytokines and histopathological changes in pancreas and liver of hyperglycemic rats by Murraya koenigii leaves extract

This study aims to investigate whether the characteristic of anti-inflammatory and protective effect of hepato- pancreascould mediate the antihyperglycemic effect of Murraya koenigii. Twenty-five Sprague-Dawley rats were inducedhyperglycemia by streptozotocin and nicotinamide (STZ-NA). The hyperglycemic rats were treated with an ethanolicextract of M. koenigii 200 mg/kg b.w and 400 mg/kg b.w. One group of the rats was treated with glibenclamide (1 mg/kg b.w). After M. koenigii extract and glibenclamide for 4 weeks, the rats were sacrificed. Blood and organ sampleswere collected under a fasting condition. The evaluation was made towards the expression of pro-inflammatorycytokines (TNF-α, IL-1β) as well as the histopathological change in the liver and pancreas. The beneficial effects ofMurraya ko enigii would bring the anti-inflammatory and hepatoprotective effect and increased the number and sizeof islet Langerhans. This research reveals that M. koenigii has a charateristic of anti-inflammatory, hepatoprotective,and it contributes to regeneration of damaged pancreatic islet. This effect is accompanied by a decrease in plasmaglucose levels

F2α-isoprostane, Na+-K+ ATPase and membrane fluidity of placental syncytiotrophoblast cell in preeclamptic women with vitamin E supplementation.

Background: The aim of our study was to analyze F2α-isoprostane level, Na+-K+ ATPase activity and placental syncytiotrophoblast cell membrane fluidity in preeclamptic women who received vitamin E supplementation. Methods: The study was conducted between September 2003 and February 2005 at Budi Kemuliaan Maternity Hospital, Central Jakarta. Samples were 6 preeclamptic women with vitamin E supplementation, 6 preeclamptic women without vitamin E supplementation and 6 normal pregnant women. The dose of vitamin E was 200 mg daily. F2α-isoprostane was measured with ELISA reader at λ of 450 nm. Cell membrane fluidity was measured by comparing the molar ratio of total cholesterol and cell membrane phospholipid concentration. The cholesterol was measured by Modular C800 using Roche reagent. Phospholipid was measured by Shimadzu RF5301PC spectrofluorometer (excitation 267 nm, emission 307 nm). Na+-K+ ATPase activity was inhibited by ouabain. Pi production was measured with Fiske and Subbarow method using spectrophotometer at λ of 660 nm. Data was analyzed using F test with one-way ANOVA. Results: Vitamin E supplementation in preeclamptic women decreased the oxidative stress, indicated by significantly lower level of F2α-isoprostane compared to those without vitamin E (26.72 ± 11.21 vs 41.85 ± 7.09 ng/mL, respectively, p = 0.017). Membrane fluidity in syncytiotrophoblast cell of preeclampsia with vitamin E group was maintained at 0.39 ± 0.08 while in those without vitamin E was 0.53 ± 0.14 (p = 0.04). Na+-K+ ATPase activity in syncytiotrophoblast cell membrane was not affected by vitamin E (p = 0.915). Conclusion: Vitamin E supplementation in preeclamptic women decreases F2α-isoprostane level and maintains cell membrane fluidity of syncytiotrophoblast cells; however, it does not increase Na+-K+ ATPase enzyme activity.

Influence of primaquine and ritonavir interaction on CYP3A4 mRNA expression in HepG2 cell culture.

Background: Concomitant treatment with antimalaria and antiretroviral drug is a new challenge in the management of malaria and HIV co-infection. Primaquine is a substrate and also an inhibitor of CYP3A4, while ritonavir is a substrate, an inhibitor, and also an inducer for CYP3A4. The objective of this study is to measure the CYP3A4 mRNA expression in HepG2 cell culture induced by primaquine and ritonavir co-treatment. Methods: For the initial study HepG2 cells were treated with 30, 40, 50 uM of primaquine; 2, 10, 20 uM ritonavir; DMSO ≤0.1 % for negative control; or 20 uM rifampicin for positive control. While for the co-treatment study the cells were treated with 40 uM primaquine+10 uM ritonavir; DMSO ≤0.1 %; or 20 uM rifampicin for 72 hours. The cells were harvested using trypsin–EDTA and total RNA was extracted using the Tripure isolation reagent. After determining the quantity of RNA spectrophotometrically, CYP3A4 mRNA expression was quantified using real-time reverse transcription polymerase chain reaction (RT-PCR). Results: The expression of CYP3A4 mRNA was up-regulated (1.22 fold over control) in HepG2 cells co-treated with primaquine and ritonavir. These data suggest that the induction effect of ritonavir was more dominant than the inhibitory effect of primaquine. Conclusion: Concomitant administration of primaquine and ritonavir result in up-regulation of CYP3A4 mRNA expression in vitro.

Interaction of erythromycin and clarithromycin with orange juice.

Concomitant administration of orange juice with fexofenadine has been found to decrease the bioavailability of fenofenadine to less than 30% via inhibition of organic-anion transporting polypeptide (OATP), a drug uptake transporter expressed in organs such as liver, kidney and intestine. Erythromycin and clarithromycin are substrates and inhibitors of CYP3A4, a drug metabolizing enzyme in the liver and enterocytes, and P-glycoprotein (P-gp), a drug efflux transporter expressed in the same organs as OATP. Since an extensive overlap exists between substrates and inhibitors of CYP3A4, P-gp and OATP transporters, we want to study the effect of coadministration of our local orange (Siam orange) juice on the bioavailability of the above antibacterials. We conducted two 2-way cross-over randomized studies, one study for each antibacterial (500 mg), crossed between administration with orange juice (200 ml) and with water, in 12-13 healthy subjects per study. The serum concentrations of the antibacterials were assayed by microbiological method. The mean (range) ratio of AUC0-t with orange juice/with water were as follows : erythromycin : total (n=13) 81.7 (9.7-193.8)%, unchanged (n=4) 96.4 (80.5-107.9)%, decreased (n=6) 31.9 (9.7-49.0)%, increased (n=3) 161.8 (134.6-193.8)%; clarithromycin : total (n=12) 91.4 (20.6-158.3)%, unchanged (n=5) 103.1 (80.9-123.0)%, decreased (n=4) 34.8 (20.6-64.3)%, increased (n=3) 147.2 (132.9-158.3)%. It was concluded that coadministration of Siam orange juice with erythromycin or clarithromycin produced unpredictable effects on the bioavailability of these antibacterials in individual subjects, with marked decreases in almost half of the subjects, although in totals the effects were not statistically significant.