Chem Biol Interact. 2004 Jan 15;147(1):49-63.
Naproxen affects Ca(2+) fluxes in mitochondria, microsomes and plasma membrane vesicles.

Salgueiro-Pagadigorria CL, Kelmer-Bracht AM, Bracht A, Ishii-Iwamoto EL.

Laboratory of Biological Oxidations, Department of Biochemistry, University of Maringa, Avenue Colombo 5790, 87020900 Maringa, Brazil.

There is substantial evidence that nonsteroidal anti-inflammatory drugs (NSAIDs) affect cellular processes regulated by Ca(2+) ions, including the metabolic responses of the liver to Ca(2+)-dependent hormones. The aim of the present study was to determine whether the effects of naproxen are mediated by a direct action on cellular Ca(2+) fluxes. The effects of naproxen on 45Ca(2+) fluxes in mitochondria, microsomes and inside-out plasma membrane vesicles were examined. Naproxen strongly impaired the mitochondrial capacity to retain 45Ca(2+) and inhibited also ATP-dependent 45Ca(2+) uptake by microsomes. Naproxen did not modify 45Ca(2+) uptake by inside-out plasma membrane vesicles, but it inhibited the hexokinase/glucose-induced Ca(2+) efflux from preloaded vesicles. Additional assays performed in isolated mitochondria revealed that naproxen causes mitochondrial uncoupling and swelling in the presence of Ca(2+) ions. These effects were prevented by EGTA, ruthenium red and cyclosporin A, indicating that naproxen acts synergistically with Ca(2+) ions by promoting the mitochondrial permeability transition. The experimental results suggest that naproxen may impair the metabolic responses to Ca(2+)-dependent hormones acting by at least two mechanisms: (1) by interfering with the supply of external Ca(2+) through a direct action on the plasma membrane Ca(2+) influx, and (2) by affecting the refilling of the agonist-sensitive internal stores, including endoplasmic reticulum and mitochondria.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14726152&dopt=Abstract Naproxen Naprosyn
[PubMed - in process]

eudoramail.com

The effect of the concentration of hydrophilic (hydroxypropyl methylcellulose [HPMC]) and hydrophobic (hydrogenated castor oil [HCO]) products, fillers (lactose and dibasic calcium phosphate), and buffers (sodium bicarbonate, calcium carbonate, and sodium citrate) on naproxen release rate was studied. Matrix tablets were prepared by double compression, and in vitro dissolution tests were performed. The dissolution results showed that an increased amount of HPMC or hydrogenated castor oil resulted in reduced drug release. The inclusion of buffers in the HPMC matrix tablets enhanced naproxen release. For HCO tablets, only sodium bicarbonate enhanced naproxen release. The presence of lactose on HPMC matrix tablets did not show a significantly different result from that obtained with the formulation containing dibasic calcium phosphate as a filler. However, for the tablets containing HCO, the presence of lactose significantly enhanced the naproxen release rate. The matrix-forming materials in this study were suitable for use in sustained-release tablets containing naproxen. The drug release can be modulated by adding suitable amounts of diluents and buffers.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14727881&dopt=Abstract Naproxen Naprosyn


deu.edu.tr

OBJECTIVE: To compare the efficacy of intrauterine lidocaine with oral naproxen sodium on pain perception of the patients during endometrial biopsy using the Pipelle instrument and to investigate their effects when used in combination. METHODS: One-hundred twenty women were randomly assigned to receive either 5 mL of intrauterine 2% lidocaine or saline and either 550 mg of naproxen sodium or a similar-appearing placebo tablet. Subsequently, each woman completed a 10-cm visual analog scale for subjective pain experience and a physician scored visible signs of the women's distress during the procedure using a 3-point observer scale. RESULTS: There was no statistically significant difference between the 4 groups in age, vaginal parity, history of chronic pelvic pain, menopausal status, tenaculum use, previous endometrial biopsy, or difficulty in passing the cervical os. The mean pain scores of the women in the naproxen only (5.8 +/- 2.2) and lidocaine only (5.9 +/- 2.2) groups were not significantly different compared with placebo group (7.1 +/- 2.0). However, the mean pain score in the lidocaine plus naproxen group (4.6 +/- 1.8) compared with the placebo group showed significant reduction in pain (P <.05). Pain rated by the physician was significantly lower in the lidocaine plus naproxen group compared with other groups, and a significant correlation was noted between the visual analog pain score and the patients' distress recorded by the physician (r =.791, P <.001). One patient in the naproxen-only group had vasovagal syncope after the procedure. CONCLUSION: Intrauterine lidocaine instillation significantly decreases pain associated with Pipelle endometrial biopsy when used in combination with oral naproxen sodium. LEVEL OF EVIDENCE: I

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14754707&dopt=Abstract Naproxen Naprosyn
[PubMed - in process]




J Pharmacol Exp Ther. 2004 Feb 25 Epub 2004 Feb 09.
Naproxen Reduces Excitotoxic Neurodegeneration In Vivo with an Extended Therapeutic Window.

Silakova JM, Hewett JA, Hewett SJ.

University of Connecticut Health Center.

The purpose of this study was to examine the optimal dose and therapeutic window of opportunity of the non-steroidal anti-inflammatory drug naproxen in an animal model of excitotoxic neuronal injury. Injection of N-methyl-D-aspartate (NMDA; 18-20nmol) into the CA1 region of the left hippocampus resulted in significant brain edema as measured by the percentage of total forebrain water content that occurred 24 hr following intrahippocampal microinjection of NMDA with approximately 50% loss of CA1 neurons assessed 72 hr later. Naproxen pretreatment (20mg/kg) resulted in significantly less brain edema. Ten, 15 or 20 mg/kg naproxen, administered systemically one day (b.i.d.) prior to and for three days after (b.i.d.) NMDA injection, attenuated the neuronal damage by 27.2 +/- 7.8%, 39.6 +/- 11.1% and 57.0 +/- 5.2%, respectively. By comparison, a single dose of MK-801 (2mg/kg, i.p.) given 20 min prior to NMDA injection inhibited subsequent hippocampal injury by 65.6 +/- 8.8%. Most importantly, neuroprotection was still evident when naproxen treatment (20mg/kg, i.p.) was initiated six hr after NMDA microinjection. Protection was lost if administration of naproxen was delayed for 20hr. These findings demonstrate that naproxen can prevent excitotoxic neuronal injury in vivo, that it is nearly as effective as direct NMDA receptor antagonism, and that it has an extended therapeutic time window. As such, naproxen may be a particularly promising pharmaceutical for the treatment of neurological diseases associated with over-activation of NMDA receptors.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14769833&dopt=Abstract Naproxen Naprosyn
[PubMed - as supplied by publisher]




Bone. 1992;13(2):167-72.
Long-term effect of naproxen on cancellous bone in ovariectomized rats.

Kimmel DB, Coble T, Lane N.

Creighton University, Omaha, NE 68131.

Previous work shows that at 42 d post-ovariectomy (OX) in aged rats, naproxen, a nonsteriodal anti-inflammatory drug (NSAID) prevents cancellous bone loss. The purpose of this study was to evaluate the effects of naproxen on cancellous bone of aged OX and sham-OX rats, at 90 days post-OX. Six-month-old Sprague-Dawley retired breeder female rats underwent either sham-OX (n = 49) or OX (n = 65). Sham-OX rats were randomized into five groups and OX rats into six groups. The first five groups of both were given ad lib access to water containing 0, 4, 10, 25, or 62.5 mg/l of naproxen sodium. The sixth group of OX rats was given water containing 156.25 mg naproxen sodium/l. After ninety days, the rats were killed following in vivo dual calcein labeling. Terminal serum naproxen was measured by HPLC. In the proximal tibial metaphysis, trabecular bone volume, trabecular thickness, trabecular number, mineralizing surface (double label), osteoclast surface, and bone formation rate were measured. Sham-OX and OX rats were compared by t-test of means. Kruskal-Wallis tests and, as necessary, Dunnett's t-tests, were applied separately to the groups of Sham-OX and OX rats. Dose-related serum levels of naproxen up to 9.4 mcg/ml were achieved in the 156.25 mg/ml group. OX rats had significantly lower bone volume, trabecular thickness, and trabecular number than Sham-OX groups (p less than .001). OX rats had significantly higher mineralizing surface, formation rate, and osteoclast surface than sham-OX rats (p less than .001). No differences related to naproxen treatment existed in sham-OX rats. Naproxen treatment producing a serum level of 9.4 mcg/ml reduced bone volume in OX rats consuming water with 156.25 mg/l (p less than .05). At 90 days post-OX, naproxen, at serum levels of 9.4 mcg/ml or less, did not diminish estrogen-depletion cancellous bone loss in rats. Naproxen lacks lasting ability to halt estrogen-depletion bone loss in aged OX rats.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1576013&dopt=Abstract Naproxen Naprosyn





Jpn J Pharmacol. 1976 Feb;(1):91-103.
Mechanism of action of a new anti-inflammatory agent, naproxen (II). Effects of naproxen on activities of mucopolysaccharase, acid protease and collagenolytic enzymes in inflamed tissues.

Suzuki Y, Ito M, Yamagami I.

In order to elucidate the biochemical anti-inflammatory properties of naproxen, the effects of this compound on activities of mucopolysaccharase [beta-glucuronidase (beta-Gase) and lysozyme (LZ)], acid protease (APase) and collagenolytic enzyme (CL) in inflamed tissues were investigated by means of a proliferative inflammatory model in filter-paper-implanted rats. In the preventive test, naproxen strongly inhibited granuloma formation and exudate accumulation as did indomethacin and prednisolone. Although the inhibitory effects of naproxen on all these enzymes were quite evident, indomethacin failed to inhibit APase activity. Prednisolone did not significantly inhibit LZ and APase activities in granuloma. In the curative test, prednisolone caused a marked decrease in the weight of the granuloma already formed and in the volume of the exudate, but with naproxen and indomethacin there was only a slight decrease. Naproxen and indomethacin induced slight but significant inhibition of LZ and CL activities, while prednisolone showing a weak inhibition of CL activity only. From these results, it may be concluded that anti-inflammatory and anti-rheumatic effects of naproxen are partly attributable to its inhibitory actions on these lysosomal enzymes.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=177800&dopt=Abstract Naproxen Naprosyn





Ophthalmic Res. 1994;26(4):226-31.
Role of naproxen as anti-oxidant in selenite cataract.

Gupta SK, Joshi S.

Dr. Rajendra Prasad Centre for Ophthalmology, All India Institute of Medical Sciences, New Delhi.

Naproxen, a nonsteroidal anti-inflammatory drug has been evaluated for its anticataract action in the prevention of cataracts induced by selenite. Administration of a single dose of sodium selenite intraperitoneally resulted in the development of advanced cataracts in 100% of the eyes within 5-6 days. Treatment with naproxen resulted in showing a significant preventive effect. The biochemical parameters like glutathione, malonaldehyde or soluble and insoluble protein contents indicate that selenite causes cataract due to oxidative stress. The observations also suggest that naproxen acts as an anti-oxidant.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7808733&dopt=Abstract Naproxen Naprosyn