COX-2 Inhibitor Meloxicam Research Articles

Evaluation of immunological response of gingival tissue injected by meloxicom

Background: Periodontitis, defined as an inflammatory disease of the supporting tissue of the teeth caused by specific microorganisms resulting in progressive destruction of the periodontal ligament and alveolar bone with pocket formation, recession or both. Although bacteria are considered to be the primary etiologic agents of periodontal disease the pathogenesis of periodontitis involves host-bacterial interaction followed by release of inflammatory mediators such as eicosanoids and cytokines . Arachidonic acid metabolites, mainly prostaglandins of the E series (PGE2), seem to be critical mediators in the progression of periodontal disease. Meloxicam inhibits prostaglandin synthetase (cylooxygenase 1 and 2) and leads to a decrease of the synthesis of prostaglandins, therefore, inflammation is reduced. Aim of the study: To evaluation of immunological parameters after sulcular injection of meloxicam on periodontium , throughout measuring the level of cytokine such as interlukine-1 beta (IL-1 beta) and tumor necrosis factor- alpha (TNF-alpha ) in blood of rabbit. Materials and Methods: Forty five male rabbits of same species were divided into three groups as following: Group1: included 20 rabbits that injected with meloxicam with a dose equivalent to human therapeutic dose using insulin syringe,. Group2: included 15 rabbits were injected with normal saline as the same volume of drug and Group3: include 10 rabbits were left without interference to be used as a control group. After sulcular injecting of meloxicam and normal saline in lower right central incisor tooth, 5 ml of blood had been collected for later analyzing of immunological analysis which include interlukine-1 beta (IL-1 beta) and tumor necrosis factor- alpha (TNF-alpha ) Results: The meloxicam injected group had produced initially higher level of TNF-α, IL-1 β than normal saline after 3 rd day of injection then there was highly significance reduction at day 14 in meloxicam injected group in compare to other groups. Conclusion: In this study, it was shown that sulcular injection of COX-2 inhibitor meloxicam reduce gingival inflammation by reducing proinflammatory mediators with no gastric damage and no remaining effect can be expected after its withdrawal. Key word: Meloxicom, periodontitis, IL-1β and TNF- α

The COX-2 inhibitor meloxicam prevents pregnancy when administered as an emergency contraceptive to nonhuman primates

ObjectiveCyclooxygenase-2 (COX-2) inhibitors reduce prostaglandin synthesis and disrupt essential reproductive processes. Ultrasound studies in women demonstrated that oral COX-2 inhibitors can delay or prevent follicle collapse associated with ovulation. The goal of this study was to determine if oral administration of a COX-2 inhibitor can inhibit reproductive function with sufficient efficacy to prevent pregnancy in primates. Study DesignThe COX-2 inhibitor meloxicam (or vehicle) was administered orally to proven fertile female cynomolgus macaques using one emergency contraceptive model and three monthly contraceptive models. In the emergency contraceptive model, females were bred with a proven fertile male once 2±1 days before ovulation, returned to the females' home cage, and then received 5 days of meloxicam treatment. In the monthly contraceptive models, females were cocaged for breeding with a proven fertile male for a total of 5 days beginning 2±1 days before ovulation. Animals received meloxicam treatment (1) cycle days 5–22, or (2) every day, or (3) each day of the 5-day breeding period. Female were then assessed for pregnancy. ResultsThe pregnancy rate with meloxicam administration using the emergency contraception model was 6.5%, significantly lower than the pregnancy rate of 33.3% when vehicle without meloxicam was administered. Pregnancy rates with the three monthly contraceptive models (75%–100%) were not consistent with preventing pregnancy. ConclusionsOral COX-2 inhibitor administration can prevent pregnancy after a single instance of breeding in primates. While meloxicam may be ineffective for regular contraception, pharmacological inhibition of COX-2 may be an effective method of emergency contraception for women. ImplicationsCOX-2 inhibitors can interfere with ovulation, but the contraceptive efficacy of drugs of this class has not been directly tested. This study, conducted in nonhuman primates, is the first to suggest that a COX-2 inhibitor may be effective as an emergency contraceptive.

Hypotension induced depressive behavior in adult mice is ameliorated by the COX-2 inhibitor meloxicam

There were no statistical differences in total fluid consumption by time of treatment. Introduction: •Mood disorders are related to both cognitive dysfunction (CD) and inflammation. Hypotension has been implicated in the development of CD following acute nitroglycerin (NTG) induced hypotension to below the level of cerebral blood flow autoregulation1. Hypotension may also associated with depression2. •Anhedonia, a hallmark of depression, may contribute to poor performance on cognitive tests. We hypothesized that anhedonia may occur after acute NTG induced hypotension and that the anti-inflammatory drug, meloxicam, a COX-2 inhibitor, would lessen the effects of hypotension by reducing the inflammatory response. •Sucrose preference testing in rodents is a standardized measure of anhedonia, the inability to experience pleasure in formally pleasurable activities.

The issues of safety and pharmacoeconomics in the management of chronic pain in the back and limbs

Nonsteroidal anti-inflammatory drugs (NSAIDs), the long-term administration of which is associated with a risk for complications, gastrointestinal tract (GIT) ones in particular, are extensively used to treat chronic pain in the back and limbs. The paper reviews the data available in the literature on adverse reactions occurring with the use of NSAIDs, discusses the issues of pharmacoeconomics in the administration of various NSAIDs. The use of the selective cyclooxygenase-2 inhibitor meloxicam (Movalis) is noted to cause fewer GIT adverse reactions than that of standard NSAIDs, the cost of treatment for GIT complications reduces.

Issues of safety and pharmacoeconomics in the treatment of chronic pain in the back and limbs

Nonsteroidal anti-inflammatory drugs (NSAIDs), the long-term administration of which is associated with a risk for complications, gastrointestinal tract (GIT) ones in particular, are extensively used to treat chronic pain in the back and limbs. The paper reviews the data available in the literature on adverse reactions occurring with the use of NSAIDs, discusses the issues of pharmacoeconomics in the administration of various NSAIDs. The use of the selective cyclooxygenase-2 inhibitor meloxicam (Movalis) is noted to cause fewer GIT adverse reactions than that of standard NSAIDs, the cost of treatment for GIT complications reduces.

Meloxicam Exerts Neuroprotection on Spinal Cord Trauma in Rats

ABSTRACTTraumatic injury to the central nervous system results in the delayed dysfunction and neuronal death. Impaired mitochondrial function, generation of reactive oxygen species (ROS), and lipid peroxidation occur soon after traumatic spinal cord injury (SCI), while the activation of compensatory molecules that neutralize ROS occurs at later time points. The aim of the current study was to investigate the putative neuroprotective effect of the COX2 inhibitor meloxicam in a rat model of SCI. In order to induce SCI, a standard weight-drop method that induced a moderately severe injury (100 g/cm force) at T10, was used. Injured animals were given either 2 mg/kg meloxicam or saline 30 min postinjury by intraperitoneal injection. At seven days postinjury, neurological examination was performed and rats were decapitated. Spinal cord samples were taken for histological examination or determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and DNA fragmentation. Formation of ROS in spinal cord tissue samples was monitored by using a chemiluminescence (CL) technique. SCI caused a significant decrease in spinal cord GSH content, which was accompanied with significant increases in CL, MDA levels, MPO activity, and DNA damage. On the other hand, meloxicam treatment reversed all these biochemical parameters as well as SCI-induced histopathological alterations. Furthermore, impairment of the neurological functions due to SCI was improved by meloxicam treatment. The present study suggests that meloxicam, reduces SCI-induced oxidative stress and exerts neuroprotection by inhibiting lipid peroxidation, GSH depletion, and DNA fragmentation.

Effect of Selective COX-2 Inhibitor on Conception Rate, Progesterone and PGFM Profile in Buffalo (Bubalus bubalis)

Rajkumar, R., Singh, S.K., Agarwal, S.K., Mahmood, S. and Shankar, U. 2010. Effect of selective COX- 2 inhibitor on conception rate, progesterone and PGFM profile in buffalo (Bubalus bubalis). J. Appl. Anim. Res, 38: 209–212. To determine the effect of selective COX-2 inhibitor (Meloxicam) on conception rate, progesterone and 13, 14-dihydro-15-keto-prostaglandin F2α(PGFM) profile, buffaloes in estrus were inseminated and divided into two equal groups. Meloxicam was injected @ 0.5 mg/kg body weight in tramuscularly on d 13, 14 and 15 post-insemination to treatment group and normal saline into control group. Conception rate was higher (20%) in the meloxicam treated buffaloes. Serum progesterone concentration did not differ (P>0.05) between the two groups. However, it was higher (P<0.05) on day 18, 21 and 24 post-insemination in pregnant animals indicating maintenance of CL and thus pregnancy. The serum PGFM concentration was (P<0.01) lower on d 15 in meloxicam treated pregnant and non-pregnant buffaloes indicating decrease in PGF2α secretion following administration of a selective COX-2 inhibitor. The results demonstrated beneficial effect of selective COX-2 inhibitor on conception rate in buffalo.

Anti-tumour effects by a trimodal combination of temozolomide, meloxicam and X-rays in cultures of human glioma cells

Purpose: To investigate the possible cytotoxic interactions between the chemotherapeutic drug temozolomide (TMZ) and the cyclooxygenase-2 inhibitor meloxicam (MLC) or of both drugs combined with X-rays in three human glioma cell lines (D384, Hs 683 and U251).Materials and methods: Cells were exposed to TMZ (96 hours) and MLC was co-incubated during the last 24 h. Thereafter, cells were irradiated with X-rays and plated for a clonogenic assay. Total cell numbers and the numbers of surviving cells were determined to study the recovery of the cell populations (up until 19 days) following different combinations of TMZ, MLC and X-rays.Results: The combination of MLC and TMZ caused an enhanced cytotoxic effect in D384 and Hs 683. Various treatment combinations demonstrated significant radiation enhancement in all three cell lines. Long-term observations of D384 cells demonstrated that the repopulation rates of the surviving cells are far less affected by the various treatment protocols than those from the non-surviving cells.Conclusions: The present study demonstrates that a combination of TMZ and MLC resulted in a significant potentiation of their cytotoxicity in D384 and Hs683. The combination of these two drugs can also cause considerable enhancement of the radiation response in human glioma cell lines, although only D384 cells benefit from trimodal over bimodal treatment.

Phase‐II trial of combination treatment of interferon‐α, cimetidine, cyclooxygenase‐2 inhibitor and renin‐angiotensin‐system inhibitor (I‐CCA therapy) for advanced renal cell carcinoma

We have recently reported favorable responses to a combination treatment comprising cimetidine, a cyclooxygenase-2 inhibitor and a renin-angiotensin-system inhibitor in metastatic renal cell carcinoma (RCC). In view of the potential synergistic effects of these three agents and interferon-α (I-CCA therapy), we conducted a phase-II trial to examine the efficacy and toxicity of I-CCA as first-line treatment. Fifty-one patients with advanced RCC received natural interferon-α (3-6 million U thrice/week) and cimetidine (800 mg), cyclooxygenase-2 inhibitor meloxicam (10 mg), and renin-angiotensin-system inhibitor candesartan (4 mg) or perindopril (4 mg) orally daily. Memorial Sloan-Kettering Cancer Center prognostic categories were favorable, intermediate and poor in 10 (20%), 31 (61%) and 10 (20%) patients, respectively. The primary end-point was the objective response rate (ORR) and the secondary end-points included clinical benefit, progression-free survival (PFS), overall survival (OS) and safety. Median follow-up was 19 months. Complete response (CR) was observed in four patients (8%) and partial response in seven (14%), yielding an ORR of 22%. None of the four patients who achieved CR relapsed during the 16- to 81-month follow up. The ORR were 17% in the favorable- or intermediate-risk group and 40% in the poor-risk group. The other 24 patients (45%) had stable disease for at least 6 months, resulting in a clinical benefit rate of 67%. The median PFS and OS were 12 and 30 months, respectively. Grade 3/4 toxicities were never observed. The I-CCA therapy, providing favorable responses and low toxicity profiles, is worthy of further consideration as a first-line therapy for metastatic RCC.

Safety of meloxicam in patients with aspirin/non‐steroidal anti‐inflammatory drug‐induced urticaria and angioedema

It has been proposed that aspirin (ASA) and other non-steroidal anti-inflammatory drug (NSAID)-induced urticaria (UR)/angioedema (AE) are mediated through inhibition of cyclooxygenase-1 (COX-1) enzymes. Therefore, drugs with COX-2 selectivity may be well tolerated in such patients. We investigated the safety of preferential COX-2 inhibitor meloxicam in subjects with UR or AE type intolerance reaction to classical ASA/NSAIDs. Subjects with reliable or documented history of UR/AE due to classical ASA/NSAIDs underwent a single-blinded, placebo-controlled oral challenge with a cumulative dose of 7.5 mg meloxicam on 2 separate days. One-quarter and three-quarter divided doses of placebo and the active drug were given at 1-h intervals. A total of 116 patients (86 women and 30 men, mean age 39.6 ± 12.7 years) were enrolled to the study. The rate of atopy was 25.9%. Mean duration of drug reaction was 87.4 ± 110.8 (1-720) months. Almost half of the patients were multi-reactors. The most comorbid disease was asthma and the two most frequent NSAIDs inducing UR/AE were paracetamol (19. 6%) and ASA (19%). No reaction to placebo was observed. Ten out of 116 patients (8.6%) developed mild UR/AE, or only erythema and pruritus at a one-quarter or cumulative dose of 7.5 mg of meloxicam. The remaining subjects (91.4%) tolerated perfectly meloxicam challenge. This study indicates that 7.5 mg meloxicam is a safe alternative for ASA/NSAID-intolerant UR/AE patients. Intolerance reactions to meloxicam are much milder forms of the patients' historical ASA/NSAID-induced cutaneous reactions.

Effect of COX-2 inhibitor meloxicam against traumatic brain injury-induced biochemical, histopathological changes and blood–brain barrier permeability

Objective: The overproduction of reactive oxygen species and resultant damage to cellular proteins or lipids of cell membranes and DNA by free radicals are the underlying mechanisms of many neuropathologies. Cyclooxygenase-2 (COX-2) inhibitors have been suggested to be neuroprotective by reducing prostanoid and free radical synthesis, or by directing arachidonic acid metabolism through alternate pathways. This study investigated the putative neuroprotective effect of the COX-2 inhibitor, meloxicam, in a rat model of diffuse brain injury.Methods: Sprague–Dawley rats were subjected to traumatic brain injury with a weight-drop device using 300 g−1 m weight–height impact. The groups were: control, meloxicam (2 mg/kg, i.p.), trauma and trauma + meloxicam (2 mg/kg, i.p.). Forty-eight hours after the injury, neurological examination scores were measured, the animals were decapitated and brain tissues were taken. Brain edema and blood–brain barrier (BBB) permeability were evaluated by wet–dry weight method and Evans blue (EB) extravasation respectively. In brain tissues, malonedialdehyde, glutathione, myeloperoxidase and Na/K-ATPase levels were measured.Results: The neurological examination scores mildly increased in trauma groups 48 hours after the induction of trauma. Meloxicam treatment improved the altered neurological status. The trauma caused a significant increase in brain water content that was partially reversed by meloxicam. Meloxicam also reduced the EB extravasation indicating the preservation of the BBB integrity. Meloxicam treatment also significantly reduced the increase in malondialdehyde and myeloperoxidase levels and restored glutathione content of the brains that had been significantly increased after trauma.Conclusion: Meloxicam exerts neuroprotective effect by preserving BBB permeability and by reducing brain edema (probably by its anti-inflammatory properties) in the diffuse brain injury model.

Peripheral and central cyclooxygenase (COX) products may contribute to the manifestation of brain-controlled sickness responses during localized inflammation induced by macrophage-activating lipopeptide-2 (MALP-2)

We investigated whether an inflammation-dependent activation of the brain occurs in response to systemic intraperitoneal (i.p.) or local injections of macrophage-activating lipopeptide-2 (MALP-2) into a subcutaneous (s.c.) air pouch, and whether local (peripheral) or central cyclooxygenase (COX)-2-dependent formations of prostaglandin E 2 (PGE 2) are involved in MALP-2-induced illness responses. Body temperature, activity, food and water intake were measured telemetrically. Local (s.c.) and circulating levels of PGE 2 were measured by an ELISA. Inflammatory activation of the brain in response to MALP-2 was determined by immunohistochemical detection of the transcription factors NFκB and STAT3 in cell nuclei as well as the appearance of COX-2 at the same sites. S.c. treatment with the preferential COX-2 inhibitor meloxicam attenuated, but not abolished fever induced by local injections of MALP-2 into the pouch. Local MALP-2-induced formation of PGE 2 was blunted by treatment with meloxicam. In the brain, i.p. stimulation with MALP-2-induced nuclear STAT3- and NFκB-translocation in the vasculature and the sensory circumventricular organs, which was accompanied by an increase in COX-2 immunoreactivity (IR) in endothelial cells. Local MALP-2-treatment induced a moderate STAT3 activation and a small but significant increase in COX-2 IR while no NFκB-activation could be observed in the brains of these animals. We demonstrated that the activation of the brain STAT3 (NFκB)-COX-2 singling cascade seems to be involved in the manifestation of brain-controlled illness symptoms induced by systemic and local inflammatory stimulation with MALP-2. The present data further suggest a contribution of peripherally produced PGE 2 to MALP-2-induced activation of brain sites implicated in fever.

The COX‐2 inhibitors, meloxicam and nimesulide, suppress neurogenesis in the adult mouse brain

In adults, neurogenesis persists in the hippocampus and the subventricular zone (SVZ), and this is important for learning and memory. Inhibitors of COX-2 suppress ischaemia-induced neurogenesis in the hippocampus. Here, we have determined the effects of COX-2 inhibitors on neurogenesis throughout the normal adult mouse brain. Young adult mice were treated with COX-2 inhibitors, and the proliferation of neural progenitor cells was measured in the SVZ and hippocampus. In addition, the local uptake of lentiviral vectors in the rostral migratory stream enabled the formation of new neurons in the olfactory bulb (OB) to be assessed. The COX-2 inhibitor meloxicam suppressed progenitor cell proliferation in the SVZ and hippocampus. A significant decrease in the appearance of new neurons in the OB was also observed. Similar effects on progenitor proliferation in the SVZ were seen with nimesulide. The absence of COX-2 expression in the proliferating progenitors in vivo, and the lack of effect of the COX-2 inhibitors on the growth rate of a cultured progenitor cell line, suggest that the effect is indirect. The specific expression of COX-2 in resting microglia that closely associate with the proliferating progenitor cells provides for a possible site of action. Treatment with a COX-2 inhibitor results in a substantial inhibition of adult neurogenesis. Studies on human tissues are warranted in order to determine if this effect extends to humans, and whether inhibition of neurogenesis should be considered as an adverse effect of these drugs.

Oral administration of the cyclooxygenase-2 (COX-2) inhibitor meloxicam blocks ovulation in non-human primates when administered to simulate emergency contraception

Prostaglandins produced via cyclooxygenase-2 (COX-2) within the periovulatory follicle are required for successful ovulation. Inhibition of follicular prostaglandin synthesis prevents timely follicle rupture and oocyte release. This study was conducted to determine if a 5-day course of oral administration of the COX-2 inhibitor meloxicam can prevent ovulation while maintaining normal menstrual cycles in non-human primates. Adult female cynomolgus monkeys were studied in each of four sequential menstrual cycles. In Cycle 1, a serum sample was obtained each day and assayed for estradiol, progesterone and luteinizing hormone; first menses was also noted to establish parameters of a normal menstrual cycle for each animal. In Cycle 2, meloxicam was administered orally once each day for 5 days beginning at either mid follicular (n = 4), late follicular (n = 4) or periovulatory (n = 4) phase of the menstrual cycle; daily serum samples and menses were assessed as for Cycle 1. In Cycle 3, the follicle-bearing ovary was removed 2 days after the expected day of ovulation (n = 3-4/treatment group). In Cycle 4, monkeys received the 5-day courses of oral meloxicam as in Cycle 2 (n = 3-4/treatment group), and the remaining ovary was removed. Ovaries were examined for the presence of an oocyte within the follicle. Monkeys had the expected levels of changing reproductive hormones during Cycle 1. Meloxicam treatment in Cycle 2 did not alter hormone levels or the luteal phase length. Follicles of ovaries removed during Cycle 3 did not contain oocytes, indicating successful ovulation. Follicles did contain oocytes after meloxicam treatment beginning in the mid follicular (67%), late follicular (100%) or periovulatory (50%) phase of Cycle 4, indicating failure of ovulation. A 5-day course of oral meloxicam administered around the time of ovulation reduced the rate of oocyte release without alteration of reproductive hormones or menstrual cycle length. Meloxicam may be effective as an emergency contraceptive in women.

Competition Between COX-2 Inhibitors and Some Other Drugs for Binding Sites on Human Serum Albumin

Competitive binding of six COX-2 inhibitors (celecoxib, valdecoxib, etoricoxib, parecoxib sodium, meloxicam and nimesulide) in the presence of three categories of drugs: an antidiabetic (gliclazide), antipsychotic (chlorpromazine) and antibiotic (ceftriaxone sodium) were studied by fluorescence spectroscopy. Data are expressed in terms of the percentage of drug bound in the absence and presence of competing drug and change in the percentage of free drug due to competitive binding. The results are discussed in terms of three cases: decrease in the binding of the parent drug; increase in binding; and no effect by the presence of the competing drug. The relative binding affinity of the parent drug and the displacing compound for human serum albumin (HSA) is not the only factor involved in the competitive mechanism. Binding behaviour of individual drugs was analysed, and explanations for different cases based on the competitive displacement, non-competitive interference, conformational changes in the HSA molecule, and independent binding are presented.

Cyclooxygenase-2 inhibition reverts the decrease in adiponectin levels and attenuates the loss of white adipose tissue during chronic inflammation

Chronic arthritis leads to a decrease in body weight that is associated with a decrease in skeletal muscle and white adipose tissue mass. We have observed that overactivation of cyclooxygenase-2 (COX-2) is responsible for muscle wasting in arthritic rats. The aim of this work was to study the role of COX-2 in arthritis-induced white adipose tissue mass loss. Arthritis was induced in rats by Freund′s adjuvant injection, and the effect of the COX-2 inhibitor meloxicam on serum concentrations of leptin, adiponectin, insulin and glycerol, as well as on gene expression of leptin, adiponectin, hormone-sensitive lipase (HSL), fatty acid synthase (FAS), tumour necrosis factor alpha (TNF) and insulin-like growth factor I (IGF-I) in white adipose tissue were determined. Arthritis decreased adipose tissue weight, serum leptin and adiponectin as well as their mRNAs in adipose tissue. Meloxicam administration to arthritic rats increased adipose tissue weight, serum concentrations of adiponectin and its mRNA in adipose tissue, but it did not modify leptin. Arthritis decreased serum insulin and FAS and IGF-I gene expression in adipose tissue. Meloxicam administration did not modify these effects. Serum concentrations of glycerol were decreased in arthritic rats. In control rats, meloxicam administration did not modify serum glycerol or adipose tissue gene expression of HSL. However, in arthritic rats HSL gene expression in adipose tissue was decreased by meloxicam. All these data indicate that COX-2 activation plays a role in the decrease in adiponectin secreted by adipocytes and in the loss in white adipose tissue mass in arthritic rats.

Comparison of the efficacy and safety of a novel meloxicam ophthalmic formulation with a reference diclofenac solution in cataract surgery

A novel topical ophthalmic formulation of the preferential COX-2 inhibitor meloxicam has recently been developed. The purpose of the present study was to evaluate the efficacy and safety of this novel 0.03% meloxicam solution with regard to a reference 0.1% diclofenac formulation in a prospective, parallel, randomized, multicenter, double-blind study. Two groups of patients submitted to phacoemulsification with intraocular lens implantation were formed. Patients in one group were treated with meloxicam and those in the other group with diclofenac. Dosing was 1 drop t.i.d. for 30 days, beginning the first day after surgery, for both treatments. Inflammation was assessed by the presence of cells in the anterior chamber, anterior chamber flare, ciliary flush, photophobia and pain. Both treatments significantly reduced these indicators. Topical meloxicam and diclofenac produced a similar degree of burning sensation and conjunctival hyperemia. There was no significant difference between treatments in any of the measured parameters. It is concluded that the novel meloxicam solution is effective and safe. Meloxicam, however, did not offer any significant benefit over the diclofenac formulation in patients submitted to cataract surgery.

Demonstration of Antiallodynic Effects of the Cyclooxygenase-2 Inhibitor Meloxicam on Established Diabetic Neuropathic Pain in Mice

Only a few experimental studies have demonstrated the effectiveness of some cyclooxygenase-2 (COX-2) inhibitors for neuropathic pain in diabetic animals. In this study we investigated the usefulness of one such COX-2 inhibitor, meloxicam, for treatment of established diabetic neuropathic pain in mice. Intraperitoneal and perineural injection, but not intrathecal injection, of meloxicam elevated the lowered threshold in the von Frey test. These results suggest that meloxicam exerts antiallodynic effects on established neuropathic pain in diabetic mice, and that the site of its action is peripheral. Meloxicam may therefore be a potentially useful drug for treatment of diabetic neuropathic pain.

Effect of selective cyclooxygenase‐2 inhibitor meloxicam on liver fibrosis in rats with ligated common bile ducts

Cholestasis triggers fibrogenesis in the liver. Hepatic cyclooxygenase-2 (COX-2) expression increases in various chronic liver diseases caused either by viruses or toxins. We hypothesized that selective COX-2 inhibitor meloxicam could suppress inflammation and fibrogenesis in a rat model of cholestasis induced by bile duct ligation (BDL). Forty-three Sprague-Dawley rats were assigned to one of four treatment groups (sham-operation, BDL, daily meloxicam injections following BDL, and daily meloxicam injection without BDL). Liver histopathology was analyzed with hematoxylin-eosin and Masson's trichrome staining. The expression of alpha-smooth muscle actin (alpha-SMA), transforming growth factor-beta1 (TGF-beta1), and COX-2 were measured with immunohistochemical staining. The levels of COX-2, TGF-beta1, and matrix metalloproteinase-9 (MMP-9) production were measured with the Western blot method and an enzyme immunoassay. Meloxicam treatment attenuated the expression of alpha-SMA, TGF-beta1, and COX-2 in rats that were treated with BDL for 3 weeks. This was associated with a marked reduction in collagen accumulation and histological improvement. In addition, meloxicam treatment was found to downregulate the levels of hepatic COX-2, TGF-beta1, and MMP-9 production. Cholestasis in BDL rats induces hepatic COX-2 expression. Selective COX-2 inhibitor meloxicam reduces BDL-induced hepatic fibrosis, and this is associated with reduced hepatic TGF-beta1 expression as well as decreased cyclooxygenase activity in the liver.

Cyclooxygenase-2 is involved in oxidative damage and alpha-synuclein accumulation in dopaminergic cells

Cyclooxygenase (COX) is the rate-limiting enzyme that catalyzes the formation of prostaglandins from arachidonic acid. The inducible isoform COX-2 is upregulated in the dopaminergic neurons of the substantia nigra of postmortem Parkinson's disease (PD) patients and in neurotoxin-induced Parkinsonism models. COX-2 has attracted significant attention as an important source of oxidative stress in dopaminergic neurons due to its potential to oxidize catechols including dopamine. However, the role of COX-2 in the pathogenesis of PD has not been fully evaluated. Here, we show that COX-2 induces dopamine oxidation, as evidenced by the findings that COX-2 can facilitate dopamine oxidation in a cell-free system and in COX-2-overexpressing SH-SY5Y cells, and that this can be completely abolished by the selective COX-2 inhibitor meloxicam. Increased COX-2 expression causes oxidative protein modification and alpha-synuclein accumulation in dopaminergic cells. These data suggest that an abnormal increase in COX-2 expression causes dopamine oxidation and contributes to the preferential vulnerability of dopaminergic cells as in PD.