Motrin
Complement and neutrophil activation in the pathogenesis of ischemic myocardial injury.

Crawford MH, Grover FL, Kolb WP, McMahan CA, O'Rourke RA, McManus LM, Pinckard RN.

Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7872.

Complement depletion with cobra venom factor (CVF) before coronary artery ligation has been previously shown to reduce subsequent ischemic myocardial tissue injury in the baboon; however, whether complement depletion after the initiation of acute myocardial ischemia affords similar myocardial preservation is not known. Both complement depletion with CVF or the administration of certain nonsteroidal anti-inflammatory drugs, including ibuprofen, are thought to decrease myocardial infarct size by reducing polymorphonuclear leukocytic (PMN) infiltration; nevertheless, complement activation also could alter tissue injury by PMN-independent actions. Thus, the relative effects of CVF administered after coronary artery ligation on the subsequent development of myocardial tissue injury were assessed in a baboon myocardial infarction model. The animals were randomized into three treatment groups (n = 6): either CVF (125 units/kg) or saline was given 30 minutes after coronary artery ligation, and ibuprofen (12.5 mg/kg) was administered 30 minutes and 4 hours after ligation. The extent of ischemic myocardial injury was assessed 24 hours later. Relative to saline-treated baboons, both CVF and ibuprofen reduced PMN infiltration (36 +/- 4 vs. 24 +/- 4 and 24 +/- 4 PMN/mm2, respectively; mean +/- SEM) and histological evidence of transmural myocardial infarction (100% vs. 47% and 53%, respectively) in electrocardiographically designated, expected infarct sites. In both saline- and ibuprofen-treated animals, there was extensive localization of C4, C3, and C5 in all infarct sites; in contrast, there was only C4 localization in the CVF-treated baboons. When expected infarct sites were assessed for creatine kinase content as an indicator of tissue injury, there was significantly less epicardial and endocardial creatine kinase depletion in the CVF-treated animals (31.7 +/- 5.6% and 39.3 +/- 4.8%) than in the saline-treated animals (54.1 +/- 5.4% and 59.0 +/- 4.7%; p = 0.012 and 0.011, respectively). The percent creatine kinase depletion in the ibuprofen-treated animals was intermediate between the two other groups. These results suggest that depletion of complement after coronary ligation has beneficial effects in reducing tissue injury that cannot be explained solely on the basis of reducing PMN infiltration into the ischemic myocardium.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3191598&dopt=Abstract ibuprofen Motrin



Motrin
Increased microvascular permeability in canine endotoxic shock: protective effects of ibuprofen.

Hubbard JD, Janssen HF.

Department of Physiology, Texas Tech University Health Sciences Center, Lubbock.

The ability of sodium ibuprofen to prevent endotoxin-induced changes in vascular permeability was examined in an anesthetized canine model. Ibuprofen was administered i.v. (3.75 mg/kg) in two pretreatment doses before the administration of Escherichia coli endotoxin (0.5 mg/kg). Serum and left thoracic duct lymph samples were collected for measurement of total protein and separation by polyacrylamide gel electrophoresis. Four protein fractions with molecular weights (MW) ranging from 60,000 to 1,000,000 were consistently analyzed. Administration of endotoxin alone resulted in hypotension and was accompanied by an increase in microvascular permeability as evidenced by increases in lymph flow rate, protein flux, lymph/plasma protein ratio (L/P), and permeability-surface area product (PS). Pretreatment with ibuprofen attenuated the increase in permeability as reflected by significantly lower lymph flow rate, protein flux, L/P, and PS. Electrophoretic data illustrate partial to complete protection for all four MW fractions. These results suggest that endotoxin damages microvascular integrity and increases extravasation of macromolecules as great as 1,000,000 MW. This damage is attenuated significantly by pretreatment with ibuprofen.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3197263&dopt=Abstract ibuprofen Motrin



Motrin
Taurine prevents Ibuprofen-induced gastric mucosal lesions and influences endogenous antioxidant status of stomach in rats.

Balasubramanian T, Somasundaram M, Felix AJ.

Department of Physiology, Rajah Muthiah Medical College, Annamalai University, Annamalainagar-608 002, Tamilnadu, India. cdl_baradear sancharnet.in

Recently, free radical-induced tissue damage is implicated in the nonsteroidal anti-inflammatory drugs (NSAIDs)-involved gastric mucosal lesion. Administration of taurine, an endogenous antioxidant, is reported to be beneficial in various clinical conditions. Therefore, we decided to study the protective effect of taurine in ibuprofen-induced gastropathy and the effects of administration of taurine on the endogenous antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX), and reduced glutathione (GSH) of stomach. In rats, administration of taurine orally for three consecutive days (250 mg/kg body weight) protected the gastric mucosa from ibuprofen-induced, acute gastric mucosal lesion. In ibuprofen-treated rats, the lipid peroxidation measured as thiobarbituric acid reactive substances (TBARS), a marker for free radical-induced tissue damage, is also significantly decreased by taurine. Ibuprofen treatment resulted in a significant increase in the activities of total SOD, manganese SOD (Mn-SOD), and GPX and reduced GSH. Taurine administration in ibuprofen-treated rats also showed a significant increase in the activities of the antioxidant enzymes namely total SOD, Mn-SOD, GPX, CAT, and the level of reduced GSH. The activity of copper-zinc SOD enzyme (Cu-Zn SOD) is not affected by ibuprofen or taurine. There is no temporal relation between the antioxidant status of the stomach and the tissue damage following oral administration of ibuprofen or taurine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15632983&dopt=Abstract ibuprofen Motrin



Motrin
Ibuprofen in experimental group B streptococcal shock.

Peevy KJ, Ronnlund RD, Chartrand SA, Boerth RC, Longenecker GL.

Department of Pediatrics, University of South Alabama, Mobile 36617.

A rabbit model was used to characterize the effects of high (Group II, 100 mg/kg) and low (Group III, 10 mg/kg) dose ibuprofen in modulating the hemodynamic and hematologic manifestations of group B streptococcal shock. Short-term survival was significantly increased with ibuprofen pretreatment. Ibuprofen failed to prevent GBS-induced shock, although shock was favorably modified in a dose dependent manner. Likewise, GBS-induced increases in 6KPGF1a and TxB2 were not prevented but were modified in Group II at 120 min. However, neutropenia, thrombocytopenia, and acidosis were not prevented by pretreatment with ibuprofen and may have been exacerbated. Thus, ibuprofen modifies but does not prevent GBS-induced hemodynamic and hematologic manifestation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3278816&dopt=Abstract ibuprofen Motrin



Motrin
Acute cigarette smoke exposure causes lung injury in rabbits treated with ibuprofen.

Witten ML, Lemen RJ, Quan SF, Sobonya RE, Magarelli JL, Bruck DC.

Department of Physiology, University of Arizona College of Medicine, Tucson 85724.

We studied lung clearance of aerosolized technetium-labeled diethylenetriamine pentaacetic acid (99mTcDTPA), plasma concentrations of 6-keto-PGF1 alpha and thromboxane B2, and pulmonary edema as indices of lung injury in rabbits exposed to cigarette smoke (CSE). Forty-six rabbits were randomly assigned to 4 groups: control sham smoke exposure (SS, N = 9), sham smoke exposure ibuprofen-pretreated (SS-I, N = 10), CSE (N = 9), sham smoke exposure ibuprofen-pretreated (SS-I, N = 10), CSE (N = 9), and CSE ibuprofen-pretreated (CSE-I, N = 19). Ibuprofen (cyclooxygenase eicosanoid inhibitor) was administered as a single daily intramuscular injection (25 mg/kg) for 7 days before the experiment. Cigarette or sham smoke was delivered by syringe in a series of 5, 10, 20, and 30 tidal volume breaths with a 15-min counting period between each subset of breaths to determine 99mTcDTPA biological half-life (T1/2). In the ibuprofen pretreated group, CSE caused significant decreases in 99mTcDTPA T1/2 and dynamic lung compliance. Furthermore, these changes in lung function were accompanied by severe injury to type I alveolar cell epithelium, pulmonary edema, and frequently death of the rabbits. These findings suggest that inhibition of the cyclooxygenase pathway before CSE exacerbates lung injury in rabbits.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3311720&dopt=Abstract ibuprofen Motrin



Motrin
Lipoxygenase and cyclo-oxygenase products in the control of regional kidney blood flow in rabbits.

Oliver JJ, Eppel GA, Rajapakse NW, Evans RG.

Department of Physiology, Monash University, Melbourne, Victoria, Australia.

1. The aim of the present study was to examine the roles of cyclo-oxygenase (COX)- and lipoxygenase (LOX)-dependent arachidonate signalling cascades in the control of regional kidney blood flow. 2. In pentobarbitone-anaesthetized rabbits treated with NG-nitro-l-arginine and glyceryl trinitrate to 'clamp' nitric oxide, we determined the effects of ibuprofen (a COX inhibitor) and esculetin (a LOX inhibitor) on resting systemic and renal haemodynamics and responses to renal arterial infusions of vasoconstrictors. 3. Ibuprofen increased mean arterial pressure (14 +/- 5%) and reduced medullary laser Doppler flux (MLDF; 26 +/- 6%) when administered with esculetin. A similar pattern of responses was observed when ibuprofen was given alone, although the reduction in MLDF was not statistically significant. Esculetin tended to increase renal blood flow (RBF; 16 +/- 7%) and MLDF (28 +/- 13%) when given alone, but not when combined with ibuprofen. 4. After vehicle, renal arterial infusions of noradrenaline, angiotensin II and endothelin-1 reduced RBF and cortical laser Doppler flux (CLDF), but not MLDF. In contrast, renal arterial [Phe2,Ile3,Orn8]-vasopressin reduced MLDF but not RBF or CLDF. Ibuprofen alone did not significantly affect these responses. Esculetin, when given alone, but not when combined with ibuprofen, enhanced noradrenaline-induced renal vasoconstriction. In contrast, esculetin did not significantly affect responses to [Phe2,Ile3,Orn8]-vasopressin, angiotensin II or endothelin-1. 5. We conclude that COX products contribute to the maintenance of arterial pressure and renal medullary perfusion under 'nitric oxide clamp' conditions, but not to renal haemodynamic responses to the vasoconstrictors we tested. Lipoxygenase products may blunt noradrenaline-induced vasoconstriction, but our observations may, instead, reflect LOX-independent effects of esculetin.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14678242&dopt=Abstract ibuprofen Motrin



Motrin
Pharmacokinetic and taste evaluation of ibuprofen (Motrin) 800 mg tablets in extemporaneous solution.

Small RE, Johnson SM, Willis HE.

Department of Pharmacy and Pharmaceutics, Medical College of Virginia, Virginia Commonwealth University, Richmond.

A 4-way crossover study was done to determine the pharmacokinetic and palatability characteristics of ibuprofen 800 mg tablets when given as a solution in various beverages. When compared to the tablet itself, no significant difference was noted for any variable measured for an orange juice solution. A delay in time-to-peak concentration (Tmax) was noted for a dilute cherry syrup solution. Changes in Tmax, peak concentration achieved and area-under-the-curve were noted with a Coca-Cola solution. The authors conclude Coca-Cola to be clearly inappropriate for this method, a dilute cherry syrup solution slightly better and orange juice to be the preferred option.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3361543&dopt=Abstract ibuprofen Motrin



Motrin
Stereoselective disposition of ibuprofen enantiomers in synovial fluid.

Day RO, Williams KM, Graham GG, Lee EJ, Knihinicki RD, Champion GD.

Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital, Darlinghurst, NSW, Australia.

The simultaneous disposition of the enantiomers of ibuprofen in synovial fluid and plasma was studied in eight patients with arthritis. Concentrations of the active S-enantiomer in synovial fluid exceeded those of the R-enantiomer at all times in all patients with the ratio of S to R concentrations being 2.1 +/- 0.3 (mean +/- SE). Synovial fluid concentrations fluctuated much less than in plasma and exceeded plasma concentrations from 5.4 +/- 0.3 hours for R-ibuprofen and 5.5 +/- 0.6 hours for S-ibuprofen. Pharmacokinetic analysis suggested that, although the enantiomers diffuse into synovial fluid primarily in the unbound form, there may be significant diffusion of the enantiomers out of synovial fluid in the protein-bound form in some patients. Interpatient differences in the disposition of the enantiomers of ibuprofen in synovial fluid were evident and may contribute to the interindividual variability in response to treatment with ibuprofen.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3365913&dopt=Abstract ibuprofen Motrin