Paroxysmal hemicrania and hemicrania continua: Review on pathophysiology, clinical features and treatment.

BACKGROUND: Paroxysmal hemicrania and hemicrania continua are indometacin-sensitive trigeminal autonomic cephalalgias, a terminology which reflects the predominant distribution of the pain, observable cranial autonomic features and shared pathophysiology. Understanding the latter is limited, both by low prevalence and the intricacies of studying brain function, requiring multimodal techniques to glean insights into such disorders. Similarly obscure is the curious response to indometacin. This review will address what is currently known about pathophysiology, the rationale for the current classification and, features which may confound the diagnosis, such as lack of cranial autonomic symptoms and those which are typically associated with migraine such as nausea, photophobia, phonophobia and aura. Despite these characteristics, a dramatic response to indometacin, which is not seen in migraine nor the other trigeminal autonomic cephalalgias , provides the hallmark of the diagnosis. The main clinical differential for paroxysmal hemicrania is based on temporal pattern and lies between cluster headache and short-lasting-neuralgiform headache attacks with tearing or additional cranial autonomic symptoms. For hemicrania continua it is more challenging as the main differential for which the disorder is often treated is migraine. A prior episodic pattern, often days at a time, and the tendency to exacerbation with analgesics will further deflect from the diagnosis. The relevance of this is that there is little overlap in therapeutics between paroxysmal hemicrania and hemicrania continua and other headache disorders and there are limited effective alternatives to indometacin. The most effective are other non-steroidal anti-inflammatory drugs including the newer COX-II inhibitors. Even though early reports suggest that a higher indometacin dose-requirement may herald a secondary precipitating pathology, this does not seem to be the case, with syndrome and response to treatment being similar with the primary disorder. In this context imaging of new onset paroxysmal hemicrania or hemicrania continua and implication of the results will be discussed as will alternative treatment options.

Underlying mechanisms of promoted formation of haloacetic acids disinfection byproducts after indometacin degradation by non-thermal discharge plasma.

Indometacin (IDM), as a kind of non-steroidal anti-inflammatory drugs, has ecological and health risks, which is the potential precursor of chlorination disinfection byproducts (DBPs). Non-thermal discharge plasma was attempted to eliminate IDM and control subsequent DBPs formation. Satisfactory removal performance for IDM was realized by the plasma oxidation; almost 100% of IDM was removed within 2 min. Relatively greater removal efficiency was gained at a higher plasma voltage and a lower pH level. Electron paramagnetic resonance spectrometer revealed that reactive species ·OH, O2·-, and 1O2 were responsible for IDM decomposition. Based on analyses of Fourier transform infrared spectroscopy, two-dimensional correlation spectroscopy, three-dimensional fluorescence spectrum, and gas chromatography-mass spectrometer, attacks of reactive species resulted in sequence breakages in functional groups of IDM, leading to production of small molecular alcohols, acids, and amines. Possible decomposition pathways of IDM were proposed. The produced acetamide and 1H-indol-5-ol were important precursors of DBPs. Formation and toxicity of nitrogen-containing DBPs were dramatically inhibited after IDM degradation; however, those of haloacetic acids were strengthened. The relevant roadmaps among DBPs and degradation intermediates were figured out. This study revealed the underlying mechanisms of IDM degradation by discharge plasma and its potential risks in chlorination disinfection.

Factors Associated With Benefit of Treatment of Patent Ductus Arteriosus in Preterm Infants: A Systematic Review and Meta-Analysis.

Context: There is an ongoing debate on the optimal management of patent ductus arteriosus (PDA) in preterm infants. Identifying subgroup of infants who would benefit from pharmacological treatment might help. Objective: To investigate the modulating effect of the differences in methodological quality, the rate of open-label treatment, and patient characteristics on relevant outcome measures in randomized controlled trials (RCTs). Data Sources: Electronic database search between 1950 and May 2020. Study Selection: RCTs that assessed pharmacological treatment compared to placebo/no treatment. Data Extraction: Data is extracted following the PRISMA guidelines. Outcome measures were failure to ductal closure, surgical ligation, incidence of necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, periventricular leukomalacia, intraventricular hemorrhage (IVH) grade ≥3, retinopathy of prematurity and mortality. Results: Forty-seven studies were eligible. The incidence of IVH grade ≥3 was lower in the treated infants compared to the placebo/no treatment (RR 0.77, 95% CI 0.64-0.94) and in the subgroups of infants with either a gestational age <28 weeks (RR 0.77, 95% CI 0.61-0.98), a birth weight <1,000 g (RR 0.77, 95% CI 0.61-0.97), or if untargeted treatment with indomethacin was started <24 h after birth (RR 0.70, 95% CI 0.54-0.90). Limitations: Statistical heterogeneity caused by missing data and variable definitions of outcome parameters. Conclusions: Although the quality of evidence is low, this meta-analysis suggests that pharmacological treatment of PDA reduces severe IVH in extremely preterm, extremely low birth weight infants or if treatment with indomethacin was started <24 h after birth. No other beneficial effects of pharmacological treatment were found.

Influence of indometacin on the level of platelet microparticles in patients with post-endoscopic retrograde cholangiopancreatography pancreatitis / 中华消化内镜杂志

To observe the effect of indomethacin suppository 100 mg before endoscopic retrograde cholangiopancreatography (ERCP) on the level of platelet microparticles (PMPs) in patients with post-ERCP pancreatitis (PEP). A total of 191 patients receiving ERCP were collected from June 2019 to October 2020 in the First Affiliated Hospital of Anhui Medical University and were randomly divided into the indometacin group ( n=96) and the control group ( n=95) by random number table method. The indometacin group received 100 mg indometacin suppositories before ERCP and the control group received placebo of equal quality. Levels of PMPs before operation, 3 hours and 24 hours after operation were measured by flow cytometry. The levels of IL-1, IL-6 and TNF-α in the plasma before ERCP, 3 hours and 24 hours after ERCP were also detected. The incidence of PEP in the indometacin group was 5.21% (5/96), which was significantly lower than that in the control group [13.68% (13/95), P=0.044]. The preoperative PMPs level in the indometacin group (1 910.01/μL) was slightly lower than that in the control group (2 351.87/μL) with no significant difference ( P>0.05). The PMPs levels in the indometacin group 3 hours and 24 hours after ERCP (1 671.47 /μL, 862.74/μL) were significantly lower than those of the control group (2 443.75/μL, 2 536.76/μL, both P<0.05). Inflammatory cytokines including IL-1, IL-6 and TNF-α showed the same tendency. Indometacin can reduce the incidence of PEP, for the reason that indometacin may decrease the levels of PMPs.

Ultrathin Ag2WO4-coated P-doped g-C3N4 nanosheets with remarkable photocatalytic performance for indomethacin degradation.

As a metal-free photocatalyst, the photocatalytic activity of graphitic carbon nitride (g-C3N4) remains restricted due to an insufficient visible-light absorption capacity, the rapid recombination of photoinduced carriers, and low surface area. Consequently, P-doped g-C3N4 (PCN) was successfully prepared via a single -step thermal polymerization technique using phytic acid biomass and urea, which exhibited remarkable photocatalytic activity for the degradation of indometacin (IDM). The IDM degradation rate was 7.1 times greater than that of pristine g-C3N4 (CN). Furthermore, Ag2WO4 was loaded onto the surface of the PCN, which formed a Z-scheme heterostructure that promoted the separation of photogenerated carriers. According to analyses of the chemical binding states of PCN, P atoms replaced carbon atoms in the CN framework. According to electron localization function analysis, the low ELF values of P-N facilitated the transfer of photoelectrons. The results of active species scavenging experiments confirmed that superoxide radicals were the primary active species in the photocatalytic degradation system. Finally, the photocatalytic degradation pathways of IDM were predicted through the identification of by-products and IDM reaction sites.

[Approach for Producing New 3,3,3-Trifluoropropenylation Reagents: Introduction of a 3,3,3-Trifluoroprop-1-enyl Group for Drug Development].

The chemistry of the 3,3,3-trifluoroprop-1-enyl (TFPE) group has attractive characteristics in medicinal chemistry as a new fluorine motif. However, there are no reports on the properties of this group because it is difficult to construct molecules with it. For the convenient construction of the TFPE group, a new fluorination reagent, CF3CH=CHTMS (1), was developed from commercially available chemicals with easy purification processes and excellent yields. The utility of 1 as a trifluoropropenylation reagent was exhibited in several types of reaction such as the Sonogashira cross-coupling reaction. Furthermore an indometacin analogue bearing a TFPE group showed greater pharmaceutical activity than the original indometacin. This review describes the details of these research studies under three topics: 1) synthesis of 1; 2) Sonogashira cross-coupling reaction of 1 with acetylene, followed by cyclization into an indole ring; and 3) synthesis of an indometacin analogue with a TFPE group.

The On-Off chiral mesoporous silica nanoparticles for delivering achiral drug in chiral environment.

In the current stage, the On-Off mechanism of chiral mesoporous silica nanoparticles (CMSN) for delivering achiral drug in chiral environment has rarely been reported. Herein, On-Off chiral mesoporous silica nanoparticles (On-Off-D-CMSN and On-Off-L-CMSN) were successfully synthesized and its particular contribution in delivering achiral drug indometacin (IMC) in chiral environment was mainly studied. The as-synthesized On-Off-D-CMSN and On-Off-L-CMSN were verified by fourier transform infrared spectrometer and circular dichroism. The transmission electron microscope test and nitrogen adsorption/desorption analysis showed that On-Off-D-CMSN and On-Off-L-CMSN were regular spheres with concealed pore channels. The zeta potential analysis demonstrated that the grafting functional groups distributed on the inner and outer surfaces of On-Off-D-CMSN and On-Off-L-CMSN. Through dissolution experiment, the drug release of IMC loaded On-Off-D-CMSN (84%) and IMC loaded On-Off-L-CMSN (70%) were about 2.4 and 2.0 times higher than pure IMC (35%) in pH 6.8 phosphate buffer solution (PBS), respectively. IMC loaded On-Off-D-CMSN and IMC loaded On-Off-L-CMSN exerted different chiral recognition functions with On-Off mechanism in in-vitro chiral environment (pH 6.8 PBS-L and pH 6.8 PBS-D). The results of anti-inflammation pharmacodynamics further demonstrated that On-Off-D-CMSN and On-Off-L-CMSN can trigger chiral biological environment to achieve on or off chiral recognition functions. The unique advantages of On-Off chiral mesoporous silica nanoparticles in triggering chiral biological environment can provide valuable instruction for designing drug delivery system.

Do etoricoxib and indometacin have similar effects and safety for gouty arthritis? A meta-analysis of randomized controlled trials.

BACKGROUND: Gout, a common medical condition that causes pain, can be treated by painkillers and anti-inflammatories. Indometacin and etoricoxib are two such drugs. However, no synthesized evidence exists comparing etoricoxib with indometacin in treating patients with gout. METHODS: We searched PubMed, Embase, Ovid MEDLINE, Web of Science, ScienceDirect, and the Cochrane Library without restrictions on language or publication date for potential randomized clinical trials comparing etoricoxib with indometacin for gout. The meta-analysis was conducted using a random-effects model. RESULTS: Search results yielded 313 references from six electronic databases, four of which met the eligibility criteria. These four were randomized clinical trials, and they involved a total of 609 patients with gouty arthritis. No significant differences were observed in pain score change, tenderness, or swelling between etoricoxib and indometacin; the mean differences were -0.05 (95% CI, -0.21 to 0.10), -0.06 (95% CI, -0.18 to 0.05), and -0.04 (95% CI, -0.17 to 0.09). However, the pooled data revealed that significantly fewer overall adverse events occurred in the etoricoxib group (n=105, 33.5%) than in the indometacin group (n=130, 44.1%) and the risk ratio was 0.77 (95% CI, 0.62-0.94). CONCLUSION: Our meta-analysis revealed that etoricoxib and indometacin have similar effects on pain relief. However, etoricoxib has a significantly lower risk of adverse events than does indometacin, especially digestive system-related adverse events.

MSNCs and MgO-MSNCs as drug delivery systems to control the adsorption kinetics and release rate of indometacin.

Mesoporous silica cocoon materials (MSNCs) and MgO doped mesoporous silica cocoons (MgO-MSNCs) with the cocoon-like hierarchical morphology and different alkalinities were synthesized as carriers for acidic drugs. Indomethacin (IMC) was selected as a model drug and loaded into carriers. All materials and the drug-loaded samples were characterized by nitrogen adsorption, FTIR spectroscopy, transmission electron microscopy (TEM), powder X-Ray diffraction (XRD) and differential scanning calorimetry (DSC). The effect of the Mg/Si molar ratio on the kinetics and equilibrium of IMC adsorption on MgO-MSNCs was thoroughly examined, and it was found that the increase in the Mg/Si molar ratio resulted in an increasing IMC adsorption rate due to the increased affinity between alkaline MgO-MSNCs and weak acid IMC. The adsorption kinetics fitted a pseudo second-order model well. The Freundlich isotherm showed a better fit, indicating that the coverage of IMC on the surface of MgO-MSNCs was heterogeneous. The maximum adsorption capacity of adsorbent was calculated by the Langmuir isotherm equation. The Temkin equation provided further support that the IMC adsorption on MgO-MSNCs was dominated by a chemisorption process. MgO-MSNCs also have the advantage of allowing an adjustment of the drug release rate of weak acid drug. The cytotoxicity assay indicated good biocompatibility of MgO-MSNCs. Our research on MgO-MSNCs carriers demonstrated their potential therapeutic benefit for safe and effective management of IMC adsorption and in vitro release.

Synthesis and characterization of hybrid Anderson hexamolybdoaluminates(III) functionalized with indometacin or cinnamic acid.

The single-side Al-centred tris-functionalized hybrid organic-inorganic Anderson polyoxomolybdates (C16H36N)3[Al(OH)3Mo6O18(OCH2)3CNH(C10H8O)]·C9H7N·4CH3OH·5H2O (AlMo6-NH-Cin; Cin is cinnamic acid, C10H9O2) and (C16H36N)3[Al(OH)3Mo6O18(OCH2)3CNH(C19H15ClNO3)]·9H2O (AlMo6-NH-Indo; Indo is indometacin, C19H16ClNO4) have been prepared in a mild three-step synthesis and structurally characterized by single-crystal X-ray diffraction, 1H NMR and IR spectroscopies and elemental analysis. Both AlMo6-NH-Cin and AlMo6-NH-Indo crystallize in the orthorhombic space group Pbca. The antibacterial activities of AlMo6-NH-Cin and AlMo6-NH-Indo against the Gram-negative human mucosal pathogen Moraxella catarrhalis were investigated by determination of the minimum inhibitory concentration, which is 32 µg ml-1 for AlMo6-NH-Cin and 256 µg ml-1 for AlMo6-NH-Indo.

Concealed body mesoporous silica nanoparticles for orally delivering indometacin with chiral recognition function.

The primary purpose of this research was to explore the potential chiral recognition functions induced by two kinds of novel concealed body mesoporous silica nanoparticles (Cb-D-MSN and Cb-L-MSN) with the entrapment of indometacin (IMC). The as-synthesized Cb-D-MSN and Cb-L-MSN were successfully fabricated through grafting molecular functional groups. The TEM result showed that Cb-D-MSN and Cb-L-MSN were regular spheres with concealed pore channels. Nitrogen adsorption/desorption analysis confirmed mesoporous structure of Cb-D-MSN and Cb-L-MSN. In vitro drug release study indicated that both Cb-D-MSN and Cb-L-MSN significantly improved IMC dissolution compared with Naked-MSN (N-MSN). Interestingly, the results of anti-inflammation pharmacodynamics and pharmacokinetics indicated that Cb-D-MSN and Cb-L-MSN exerted different chiral recognition functions, which Cb-D-MSN can deliver more IMC evidenced by molecular simulations. It is expected that the herein favorable carriers with unique advantages in triggering chiral biological environment can be promising for constructing drug delivery system.

Colonic delivery of indometacin loaded PGA-co-PDL microparticles coated with Eudragit L100-55 from fast disintegrating tablets.

The aim of this work was to investigate the efficient targeting and delivery of indometacin (IND), as a model anti-inflammatory drug to the colon for treatment of inflammatory bowel disease. We prepared fast disintegrating tablets (FDT) containing IND encapsulated within poly(glycerol-adipate-co-É·-pentadecalactone), PGA-co-PDL, microparticles and coated with Eudragit L100-55 at different ratios (1:1.5, 1:1, 1:0.5). Microparticles encapsulated with IND were prepared using an o/w single emulsion solvent evaporation technique and coated with Eudragit L-100-55 via spray drying. The produced coated microparticles (PGA-co-PDL-IND/Eudragit) were formulated into optimised FTD using a single station press. The loading, in vitro release, permeability and transport of IND from PGA-co-PDL-IND/Eudragit microparticles was studied in Caco-2 cell lines. IND was efficiently encapsulated (570.15±4.2µg/mg) within the PGA-co-PDL microparticles. In vitro release of PGA-co-PDL-IND/Eudragit microparticles (1:1.5) showed significantly (p<0.05, ANOVA/Tukey) lower release of IND 13.70±1.6 and 56.46±3.8% compared with 1:1 (89.61±2.5, 80.13±2.6%) and 1:0.5 (39.46±0.9 & 43.38±3.12) after 3 and 43h at pH 5.5 and 6.8, respectively. The permeability and transport studies indicated IND released from PGA-co-PDL-IND/Eudragit microparticles had a lower permeability coefficient of 13.95±0.68×10-6cm/s compared to free IND 23.06±3.56×10-6cm/s. These results indicate the possibility of targeting anti-inflammatory drugs to the colon using FDTs containing microparticles coated with Eudragit.

Oxidation of indometacin by ferrate (VI): kinetics, degradation pathways, and toxicity assessment.

The oxidation of indometacin (IDM) by ferrate(VI) (Fe(VI)) was investigated to determine the reaction kinetics, transformation products, and changes in toxicity. The reaction between IDM and Fe(VI) followed first-order kinetics with respect to each reactant. The apparent second-order rate constants (k app) decreased from 9.35 to 6.52 M-1 s-1, as the pH of the solution increased from 7.0 to 10.0. The pH dependence of k app might be well explained by considering the species-specific rate constants of the reactions of IDM with Fe(VI). Detailed product studies using liquid chromatography-tandem mass spectrometry (LC-MS/MS) indicated that the oxidation products were primarily derived from the hydrolysis of amide linkages, the addition of hydroxyl groups, and electrophilic oxidation. The toxicity of the oxidation products was evaluated using the Microtox test, which indicated that transformation products exhibited less toxicity to the Vibrio fischeri bacteria. Quantitative structure-activity relationship (QSAR) analysis calculated by the ecological structure activity relationship (ECOSAR) revealed that all of the identified products exhibited lower acute and chronic toxicity than the parent pharmaceutical for fish, daphnid, and green algae. Furthermore, Fe(VI) was effective in the degradation IDM in water containing carbonate ions or fulvic acid (FA), and in lake water samples; however, higher Fe(VI) dosages would be required to completely remove IDM in lake water in contrast to deionized water.

Pharmacokinetics of Indometacin Enteric-coated Dropping Pills in Beagle Dogs / 中国药师

Objective:To study the pharmacokinetics of indometacin (IDM) enteric-coated dropping pills.Methods:Beagle dogs were used as the experimental animals and the marketed IDM enteric-coated tablets were applied as the control,the pharmacokinetics of IDM enteric-coated dropping pills was studied after a single oral administration.DAS software was used for the model fit and parameter calculation,and the bioequivalence was also evaluated.Results:Both IDM enteric-coated dropping pills and tablets were fitted a one-compartment model.Compared with those of IDM enteric-coated tablets,the Cmax,Tmax,AUC0-∞and Tlag of IDM enteric-coated dropping pills all showed notable differences (P<0.05),and the former two increased significantly,and the latter two were shortened significantly.The relative bioavailability of the dropping pills was (121.0±7.7)%.Conclusion:Compared with IDM enteric-coated tablets,IDM enteric-coated dropping pills are with significantly enhanced absorption and shortened lag time,which is worthy of further studies and development.

Simultaneous Determination of Two Components in Furazolidone, Indometacin and Cuscohygrinolis α-Acetylbenzoacetate Suppositories by HPLC with Dual Wavelength Detection / 中国药师

Objective:To establish an analytical method for the determination of furazolidone and indometacin in furazolidone, in-dometacin and cuscohygrinolis α-acetylbenzoacetate suppositories by HPLC. Methods: The separation was performed on a ZORBAX Extend-C18 (250 mm × 4. 6 mm,5μm) column. The mobile phase was acetonitrile and 0. 035 mol·L-1 potassium phosphate monobas-ic aqueous solution (adjusting pH to 3. 0 with acetic acid) with gradient elution. The flow rate was 1. 0 ml·min-1, and the detection wavelengths were set at 364 nm and 318 nm. The column temperature was 30℃ and the injection volume was 20 μl. Results:Under the selected chromatographic conditions, the two components showed good linearity within the range of 0.005-0.05 mg·ml-1(r=0. 9999). The limit of detection was 20 ng·ml-1 and 26 ng·ml-1, respectively. The limit of quantitation was 70 ng·ml-1 and 90 ng·ml-1, respectively. The average recovery was 99. 4％(RSD=0. 6％, n=9)and 99. 4％(RSD=0. 3％,n=9),respectively. Conclusion:The method is simple, rapid and specific, and the results are accurate and reliable. The method can be used for the de-termination of the two components in furazolidone, indometacin and cuscohygrinolis α-acetylbenzoacetate suppositories.

Simultaneous Determination of Two Ingredients in Indometacin and Furazolidone Suppositories by HPLC / 中国药师

Objective: To establish an HPLC method for the simultaneous determination of two ingredients in indometacin and furazolidone suppositories.Methods: The analysis was performed on an XTerra(R) RP18 column (250 mm×4.6 mm, 5 μm) with gradient elution of methanol and 0.01 mol·L-1 potassium dihydrogen phosphate-triethylamine (100∶0.02) at the flow rate of 1.0 ml·min-1.The column temperature was 30 ℃ and the detection wavelength was 263 nm.The injection volume was 10 μl.Results: The peaks of furazolidone and indometacin were successfully separated.The linear range of calibration curves was 5.12-81.87 μg·ml-1 (r =1.0000) and 3.78-60.45 μg·ml-1 (r =1.0000), respectively.The average recovey was 99.6% (RSD =1.5%, n =6) and 100.3% (RSD =1.6%, n =6), respectively.The limit of quantification (LOQ) was 0.02 μg·ml-1 and 0.05 μg·ml-1, respectively.Conclusion: The established method is validated to be suitable for the quality control of indometacin and furazolidone suppositories.

Characterization of Indomethacin Enteric-coated Dropping Pills / 中国药师

Objective: To study the status of indomethacin (IDM) in IDM enteric-coated dropping pills and its interaction with PEG 6000.Methods: IDM, PEG 6000, their physical mixture and IDM enteric-coated dropping pills were respectively studied by DSC, IR, X-ray diffraction and SEM.Results: In the map of DSC, the endothermic peak of IDM enteric-coated dropping pills disappeared at 164℃, and the endothermic peak of PEG 6000 at 57℃ shifted forward.In the map of IR, the carbonyl stretching vibration peak of IDM in IDM enteric-coated dropping pills disappeared, and a new peak appeared at 1 680 cm-1.In the map of X-ray diffraction, there was no diffraction peak in IDM enteric-coated dropping pills.SEM showed the morphology of IDM in the base was much smaller than that of IDM raw material.Conclusion: IDM in IDM enteric-coated dropping pills is dispersed in the matrix with an amorphous or molecular form, and there is hydrogen bond between IDM and PEG 6000.

Efficient approach to enhance drug solubility by particle engineering of bovine serum albumin.

The aim of this study was to investigate the use of bovine serum albumin (BSA) as a solubility enhancer for indometacin (IND) as a model drug. IND-BSA solid dispersions were prepared by both spray drying and freeze drying techniques using IND:BSA solution (20:1 Molar Ratio (MR)) and IND:BSA suspension (100:1 MR). The solid state of IND in solid dispersions was characterised by SEM, DSC and XRD. The aqueous solubility of IND in the presence of increased amounts of BSA was evaluated. Additionally, IND dissolution and release profiles were evaluated. IND in solid dispersions with BSA showed significantly higher solubility in water than that of the physical mixture of both. Enhancement factors of 24,000 and 100,000 were obtained for the solid dispersion formulated in 20:1 MR and 100:1 MR, respectively. Dissolution studies in-vitro indicated a significant increase in the dissolution rate of IND from solid dispersions compared to that of the free drug, with almost 95% of the drug dissolved in the first 5min. Furthermore, an immediate release of IND from BSA solid dispersions was shown. The potential use of albumin as solubility enhancer for poorly soluble drugs, particularly, for immediate release volume-limited dosage forms is reported.

In Vitro Cytotoxic Effects of Celecoxib, Mefenamic Acid, Aspirin and Indometacin on Several Cells Lines.

STATEMENT OF THE PROBLEM: Use of cyclooxygenase inhibitors as chemotherapy agents has attracted the attention of a large number of investigators in recent years. Given the importance of cancer therapy, only a limited number of studies have been carried out to investigate the effects of cyclooxygenase inhibitors on specific cell lines. PURPOSE: This research aimed to determine the in vitro cytotoxic effects of cyclooxygenase inhibitors (COX-1 and COX-2 inhibitors) on KB, Saos-2, 1321N, U-87MG, SFBF-PI 39 cell lines. MATERIALS AND METHOD: Powders of celecoxib, mefenamic acid, aspirin and indometacin were dissolved in the appropriate solvent. The viability of cell lines was carried out by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay technique. Data gathered from four separate experiments were expressed as mean±SD. Statistical significance was defined at p< 0.05 by using analysis of variance. Significant treatment mean values were subjected to post-hoc Tukey's test. RESULTS: Celecoxib showed marked cytotoxic effects on KB, Saos-2, and 1321N cells, which was significant in comparison with the control group. Celecoxib was not effective in killing U-87MG cell line. Mefenamic acid exerted cytotoxic effects on KB, Saos-2, and 1321N cells, where the viability was approximately 75%. U-87MG cells were resistant to mefenamic acid. Indometacin had the highest rate of activity on U-87MG cells, which was significant in comparison with the control group. Aspirin did not exhibit any activity on these cell lines and was not effective in killing U-87MG, KB, Saos-2, and 1321N cells. CONCLUSION: This research showed that celecoxib, indometacin, and mefenamic acid have the cytotoxic effects on KB, Saos-2, 1321N and U-87MG cell lines. Therefore, it appears that these drugs can be considered as anti-neoplastic agents in the experimental phase.