Determination of Captopril in Rat Plasma by LC-MS/MS in Presence of Apigenin

To determine and validate of captopril in presence of apigenin by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in rat plasma. The captopril and apigenin were extracted from rat plasma by protein precipitation with acetonitrile. Sample containing captopril and apigenin were analyzed by using LC-MS/MS with C18 column Acquity® (100 mm×2�1 mm), 1.7 �m particles size column at 40 �C. The gradient system of mobile phase composition was a mixture of 0.1% formic acid and acetonitrile (60; 40 v/v), with flow rate 0.3 ml/second. Mass detection was performed on Waters Xevo Triple Quadrupole equipped with an electrospray ionization (ESI) source in positive ion mode in the multiple reaction monitoring (MRM) modes. Captopril was detected at m/z 415 > 216�16, apigenin was detected at m/z 271�13 > 153�07 and propranolol an internal standard was detected at m/z 260 > 183�17. Results: The method was validated according to EMEA guidelines which showed good reproducibility and linearity of 0.9992, the LLOQ were 10 ng/ml for captopril. The precision (%CV) value of Within-run and between-run analysis is 3.90–10.90% and 3.77–8.13% whereas the accuracy (%diff) of captopril was less than 20%. Stability studies revealed that captopril has been stable for 6 hours at room temperature, three freeze-thaw cycles, and at least 120 days at −40 �C. Conclusion: The developed LC-MS/MS method is valid to evaluate captopril in present of apigenin in vitro and meet the requirement of linearity, accuracy, selectivity, precision, matrix effect, and stability according to EMEA 2011

The Improving of Methylprednisolone Palmitate Potency After Incorporated with Liposome - an Antiinflammation Study in Culture of Mice\u27s Splenocytes

Glucocorticoid has been used as an antiinflammatory and immuno-suppresive drug. Longterm utilisation at high dose of glucocorticoid is associated with serious side effects. In recent years, many attempts have been performed in searching the appropiate vehicles to deliver the drug directly into the target organ or the receptor. By incorporating the drug into its vehicle such as liposome, the systemic side effect can be minimized. Purwaningsih et al has successfully synthetized a novel preparation of liposome methylprednisolone palmitate (L-MPLP). The aim of the study was to learn the pharmacological effect of L-MPLP, especially on antiinflammatory effect of this novel preparation, compared with the standard methylprednisolone (MPL). The parameter was the potency of L-MPLP in reducing gamma-interferon production in T-lymphocyte culture after stimulation with concanavalin A in vitro as well as in vivo. Gamma-interferon was assayed by ELISA method. The reduction of gamma interferon, in vivo, after the administration of L-MPLP at the dose of 2,8 and 16 mg/kgBW respectively, showed significant difference than a control group, while MPL did not. The addition of both L-MPLP and MPL in in vitro culture at the concentration of 5.10-3, 5.10-2 and 5.10-1 mM have proved to suppress the gammainterferon production, where the suppression of L-MPLP was more effective than MPL, significantly

Oral Ferrous Sulphate Improves Functional Capacity on Heart Failure Patients with Iron Deficiency Anemia

Background: Iron deficiency anemia (IDA) in heart failure (HF) is associated with poor functional capacity. Several studies reported the benefit of iron therapy in HF with IDA on improving functional capacity. Therefore, we attempt to investigate the effect of oral iron supplementation on functional capacity in HF patients with IDA. Results: Double blind randomized controlled trial was conducted in National Cardiovascular Center Harapan Kita Hospital Universitas Indonesia. A total 54 HFREF patients with IDA were enrolled and randomized to either oral Ferrous Sulphate (FS) 200mg 3 times a day or placebo with 1:1 ratio for 12 weeks. Primary outcome was functional capacity measured by 6-minute walk test. There were 41 participants completed the study (FS n=22, placebo n=19). Ferrous sulphate significantly improved functional capacity changes (46.23+35m vs -13.7+46m, p<0.001, CI -86.8 to -33.2) compared with placebo groups respectively after 12 weeks intervention. Conclusions: Oral FS supplementation for 12 weeks significantly improved functional capacity in HF patients with IDA. Trial registration: clinicaltrials.gov, NCT02998697. Registered 14 December 2016 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT0299869

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. (Med J Indones. 2012;21:225-9)Keywords: F2α-isoprostane, membrane fluidity, Na+-K+ ATPase, preeclampsia, vitamin E</p

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. (Med J Indones. 2012;21:225-9)Keywords: F2α-isoprostane, membrane fluidity, Na+-K+ ATPase, preeclampsia, vitamin E</p

Effect of Apium graveolens Extract Administration on the Pharmacokinetics of Captopril in the Plasma of Rats

Apium graveolens (celery) is an edible and traditionally medicinal plant that is used worldwide, among others for the treatment of hypertension. Combining celery with antihypertensive drugs can affect the pharmacodynamics and pharmacokinetics of the latter drugs. The aim of the study is to assess the effects of administrating the celery extract on captopril pharmacokinetics. Sprague-Dawley strain rats were divided into two groups (n = 6). Group I was given captopril (10 mg/kg Body Weight (BW)) orally, while Group II was pretreated with celery extract orally (40 mg/kg BW) an hour before administration of captopril. The blood samples were withdrawn at various intervals after drug administration. The captopril concentration was determined using liquid chromatography–mass spectrometry (LC-MS/MS) and from the blood data, the values of Ke, Cmax, Tmax, T1/2, and area under the curve (AUC) were calculated. The results showed that oral administration of the celery extract increased Cmax (38.67%), T1/2 (37.84%), and AUC (58.10%) and decreased Ke (27.45%) of captopril in Group II (celery + captopril) compared with Group I (captopril). In conclusion, celery extract can alter the pharmacokinetic of captopril when given in combination. The combination might be beneficial for the treatment of hypertension, as celery causes an increase in the plasma level of captopril, which can enhance its efficacy

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. (Med J Indones 2012;21:3-7)Keywords: CYP450 induction, CYP3A4, drug interaction, primaquine, ritonavir</p

IN SILICO IDENTIFICATION TESTING OF TRITERPENE SAPONINES ON CENTELLA ASIATICA ON INHIBITOR RENIN ACTIVITY ANTIHYPERTENSIVE

The renin-angiotensin-aldosterone system (RAAS) has an essential role in the occurrence of hypertension. Two drugs that act on SRAA are ACE Inhibitor and ARB. ACE inhibitor and ARB are two antihypertensive drugs that act on RAAS. However, both drugs are not fully effective because they produce incomplete suppression of RAAS. The therapeutic potential of the two drugs is limited, so it is necessary to find out other drugs that are more effective in inhibiting the RAAS system. Renin-inhibitors are evolving as options that can inhibit at the highest levels in RAAS. Discontinuation of renin inhibitor therapy does not cause rebound hypertension as in ACEIs and ARBs. The search for natural renin inhibitors began to be carried out as an alternative to aliskiren. Renin-inhibitors derived from natural ingredients generally come from the class of saponin compounds or polyphenol compounds. One of Indonesia's native plants that contain saponins and polyphenols is Centella asiatica. Thus, research on the antihypertensive potential of these plants was carried out. It is expected that the Centella asiatica plant has a renin inhibitor effect as a blood pressure-lowering drug derived from herbs but has the same effect as aliskiren. The research method was carried out in silico to test the activity of compounds that have potential as antihypertensives in the Centella asiatica plant. The method used is molecular docking, with the docking software used being Molegro Virtual Docker (MVD) 6.0. The results showed that madecasoside and asiaticoside from the Centella asiatica plant have intense renin inhibitor activity, with a mean re-rank score of-105.27 and-93.67, respectively. The conclusion is that madecasoside has similarities with aliskiren with a re-rank value of-105.27. The smallest re-rank value indicates the similarity and strong protein binding between the tested ligand compound and the comparison protein

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. (Med J Indones 2005; 14: 78-86) Keywords: interaction, erythromycin, clarithromycin, orange juice

The effects of Curcuma against paracetamol-induced liver damage in rats

[no abstract available