Anti-inflammatory Activity Of Indomethacin Research Articles

Alpha‐lipoic acid: A promising adjuvant for nonsteroidal anti‐inflammatory drugs therapy with improved efficacy and gastroprotection

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in a wide variety of diseases due to their analgesic and anti-inflammatory effects, but their usage have been limited due to significant ulcerogenic side effects. In the present study, we aimed to evaluate the effect of α-lipoic acid (ALA) treatment on the anti-inflammatory activity of indomethacin (Indo) as well as the possible therapeutic effect of ALA on high dose Indo-induced gastropathy in female mice. Mice were treated with Indo (5 or 30 mg/kg, p.o) alone or in combination with ALA (50, 100 or 200 mg/kg, i.p). in vivo anti-inflammatory effect was evaluated by formalin-induced paw edema measured as paw thickness and edema. Gastric damage was evaluated macroscopically and histologically by scoring mucosal hemorrhage, erosion, edema and inflammation. To our results, Indo was ineffective at 5mg/kg, but co-treatment with Indo and ALA significantly reduced paw edema, implying that ALA augmented the anti-inflammatory effect of subtherapeutic dose of Indo. However, ALA was not able to induce a further increase in the anti-inflammatory effect of Indo at 30 mg/kg. Unlike the treatment with Indo at 5mg/kg, Indo at 30 mg/kg caused severe gastric damage that prevented by co-treatment with ALA. These results suggest that combination of ALA with NSAIDs can both increase anti-inflammatory effect and prevent NSAIDs-induced gastric damage. ALA would be promising adjuvant that can reduce dose for effective NSAID therapy, which improves safety profile of NSAIDs especially in cases long-term administration of high dose needed.

Evaluation of Therapeutic Efficacy of Vinpocetine in Adjuvant Induced Arthritis Model in Rats

Introduction: Rheumatoid Arthritis (RA) is an incurable chronic inflammatory disorder. Indomethacin is used for symptomatic management of RA; its long term use is associated with potentially life-threatening deleterious side effects. Vinpocetine is an alkaloid extracted from the periwinkle plant used for treating cerebrovascular disorders with no significant side effects. Recent evidences demonstrate its anti-inflammatory properties. Objective: To evaluate the anti-inflammatory, analgesic and neuroprotective activities of vinpocetine against RA as well as the associated neurological disorders and to investigate its influence on the anti-inflammatory activity of indomethacin in rats. Methods: Complete Freund’s adjuvant induced arthritic rats were treated for 3 weeks with indomethacin (1, 2 mg/ kg P.O.) and/or vinpocetine (20 mg/kg P.O.). Body weight, ankle diameter, arthritic score, serum tumor necrosis factor alpha (TNF-α) and interleukin one beta (IL-1β), tissue expression of nuclear factor kappa B (NF-κB) were determined and gait score were assessed. Brain monoamines levels and behavior in the swimming test were also measured. In addition, histopathological examinations of hind paw and brain tissues as well as X-ray examinations of the paw were performed. Results: Combination therapy of vinpocetine with indomethacin significantly improved analgesic and inflammatory parameters as compared to indomethacin alone. Vinpocetine alone decreased the inflammatory markers in the same extent as indomethacin. In some parameters, vinpocetine has equal effect as the combination therapy. It also decreased swimming time while increased direction score together with increased brain norepinepherine and serotonin as well as serum total anti-oxidant capacity (TAC) level. Histopathological and X-ray examinations supported these results. Conclusion: Vinpocetine has potent anti-arthritic, anti-inflammatory and anti-nociceptive effects. It also potentiates the anti-inflammatory action of indomethacin. It also improves RA associated depression. Thus, it can be used either alone or in combination with indomethacin to avoid or to decrease the serious side effects of indomethacin and to improve RA associated depression.

Self-Nanoemulsifying Drug Delivery Systems Based on Melon Oil and its Admixture with a Homolipid from Bos indicus for the Delivery of Indomethacin

Purpose: To formulate self-nanoemulsifying drug delivery systems (SNEDDS) based on melon oil and its admixture with a homolipid from Bos indicus (cow fat) for the delivery of indomethacin, a hydrophobic anti-inflammatory agent. Method: Melon oil and cow fat were extracted by standard methods and used in the formulation of SNEDDS based on either melon oil alone, or its admixture with cow fat by utilizing varying ratios of oil(s), surfactants and co-surfactants, with or without carbosil, a glidant. The formulations were encapsulated in hard gelatin capsules and then evaluated using relevant parameters including isotropicity tests, dilution stability, precipitation propensity, emulsification time, absolute drug content, in vitro drug release, and anti-inflammatory activity in an animal model. Results: Stable and negatively charged colloidal dispersions (zeta potential: -10.4 to -13.4 mV) in the nano size range (195 - 210 nm) were formed. Formulation of indomethacin as SNEDDS not only preserved the activity of the drug, but also guaranteed anti-inflammatory activity comparable to that of indomethacin injection. The inhibition produced by the drug-loaded SNEDDS and the positive control were identical for much of the 5 h test period, indicating a high degree of bioavailability of the administered SNEDDS formulation. Conclusion: A 1:1 ratio of melon oil and cow fat could be used in the formulation and delivery of indomethacin-loaded SNEDDS with satisfactory properties and acceptable product performance. The anti-inflammatory activity of indomethacin was preserved in the formulation.

Percutaneous absorption and anti-inflammatory activity of indomethacin in ointment.

A jelly-type ointment containing 1% indomethacin, ID gel, was prepared, and the anti-infla-mmatory effects and percutaneous absorption of ID gel were studied. ID gel inhibited carrageenin-induced paw edema concentration-dependently by topical application and showed significant effect at concentratin over 1%. ID gel inhibited inflammation only in the applied foot, but did not influence the edema of non-applied foot in car-rrageenin-induced edema experiments. It was shown that percutaneous absorption of indomethacin was markedly more into the exudate and muscle of the applied foot than those of non-applied foot and systemic blood. ID gel showed also anti-inflam-matory erects on adjuvant arthritis in rats and ultraviolet-induced erythema in guinea pigs.

Reason for the aggravation of diseases caused by inflammation and the ineffectiveness of NSAIDs on these diseases in rainy weather

In this study, the anti-inflammatory activity of indomethacin, diclofenac, meloxicam and nimesulide were investigated on sunny and rainy days. Parallel to these experiments, the question of whether endogenous adrenaline and cortisol (corticosterone in rats) are factors that affect medicinal activity of these anti-inflammatory drugs on sunny and rainy days was examined. Our experimental results show that the drugs used produced significant anti-inflammatory effects on sunny days (76.5, 62.8, 56.9 and 64.7%, respectively) but were less effective on rainy days. On sunny days, adrenaline levels decreased by 83–86% in the groups that received indomethacin, diclofenac, meloxicam or nimesulide, compared to the control group. In contrast, there was no significant difference in corticosterone levels in any of these groups. In addition, the adrenaline and corticosterone levels of intact (versus adrenalectomized) rats decreased by 83% and 58.8%, respectively, on rainy days compared to sunny days.Indomethacin, diclofenac, meloxicam and nimesulide were found to exert anti-inflammatory effects by decreasing adrenaline levels but not affecting corticosterone levels. The anti-inflammatory effects of the tested drugs was eliminated on rainy days due to the low level of corticosterone.

Indomethacin-loaded poly ( d,l-lactide) nanocapsules protection from gastrointestinal ulcerations and anti-inflammatory activity evaluation in rats

Indomethacin-loaded nanocapsules were prepared by deposition of poly ( d,l-lactide) polymer (PLA) at the oil/water interface following acetone displacement from the oily nanodroplets. Rapid in-vitro release profiles of indomethacin from PLA nanocapsules were observed at pH above 7·0 Nanoencapsulation of indomethacin induced a marked protective effect on the gastro-intestinal tissues as compared to the ulcerative effect observed with the aqueous solution of the drug following three consecutive oral daily doses of 10 mg/kg. It was shown that the induced protective effect displayed by the PLA nanocapsules was rather associated with low tissue concentration than with high plasma concentration. The incorporation of indomethacin in the PLA nanocapsules did not alter the pharmacological activity of the drug, since similar edema inhibition profiles were observed for the aqueous solution and for the PLA nanocapsules using the carrageenininduced edema test in the hind paw of rats. Furthermore, the anti-inflammatory activity of indomethacin was enhanced following incorporation in the PLA nanocapsules. Two possible explanations were proposed for the overall result interpretations.

Anti-inflammatory activity of indomethacin in copper deficient rats

Anti-inflammatory activity of indomethacin in copper deficient rats

Cod liver oil inhibits indomethacin induced gastropathy without affecting its bioavailability and pharmacological activity

The upper gastrointestinal toxicity is one of the most common side effects associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs). Many attempts to prepare potent NSAIDs free from gastrotoxicity have failed. Hence, development of formulations to mask the gastropathy of NSAIDs are warranted. The present study was undertaken to investigate the effect of concomitant use of cod liver oil (CLO) on pharmacological activity and gastropathy of indomethacin in rats. The animals were treated with CLO (5 and 10 ml/kg body weight) along with indomethacin (30 mg/kg, body weight). Blood samples were collected for analysis of indomethacin at 0.25, 0.5, 1.5, 2.0, 4.0, 6.0 and 24 hours. The anti-inflammatory activity of indomethacin alone and in combination with CLO was studied using carrageenan-induced paw oedema. Our studies related to the effect of these drugs on gastrointestinal tract showed that concurrent use of CLO protects gastric mucosa against indomethacin induced depletion of gastric wall mucus, non protein sulfhydryl (NP-SH) levels and gastric lesions. The result of this study also showed that the concurrent use of the CLO does not affect the bioavailability and anti-inflammatory activity of indomethacin while it inhibits the ulcerogenic effect of indomethacin in a dose dependent manner. These findings suggest that NSAIDs formulations containing CLO may reduce gastrotoxicity without affecting their therapeutic efficacy.

The Inhibition of Mitochondrial Respiration by Indomethacin, a Non-Steroid Anti-Inflammatory Agent Possessing Inhibitory Effect on Prostaglandin Biosynthesis

It was found that indomethacin, a potent inhibitor to cyclo-oxygenase in prostaglandin biosynthesis system, disturbed mitochondrial respiration and its farnesyl ester, E-0710 which no longer exhibited the inhibitory effect on cyclo-oxygenase, did not affect the mitochondrial respiration, indicating a good correlation between the inhibitory effect on ATP biosynthesis in mitochondria and the anti-inflammatory activity of indomethacin.

The influence of experimental hypo- and hyperthyroid states on acute and chronic inflammatory reactions: modified response to non-steroidal anti-inflammatory agents.

Hyperthyroid and hypothyroid states were induced in rats by administration of triiodothyronine or surgical thyroparathyroidectomy. The anti-inflammatory activity of Indomethacin, Oxametacine and Phenylbutazone was evaluated in these animals using paw oedema provoked by carrageenan granulomas induced by cotton pellets and polyarthritis induced by Freund complete adjuvant. Our results indicate that the hyperthyroid state leads to a significant inhibition of the acute inflammatory response to carrageenan, while hypothyroidism has no effect. There was a marked increase in the anti-inflammatory activity of Indomethacin and Phenylbutazone in hyperthyroid rats. By contrast, in thyroparathyroidectomised animals the anti-inflammatory effect of these drugs appeared less than in euthyroid rats. The hyperthyroid state slightly inhibited the development of the cotton pellet-induced granuloma, while hypothyroidism enhanced it. Treatment of hypothyroid animals with the anti-inflammatory drugs resulted in a significant decrease in the size of the granuloma. In the hyperthyroid state, the activity of the compounds appeared similar to that detected in euthyroid rats. Neither hyperthyroidism, nor hypothyroidism affected the inflammatory response to mycobacterial adjuvant, or the effect of anti-inflammatory drugs on the response. These results suggest that thyroid hormones may influence, to various degrees the development of acute inflammation due to carrageenan, and chronic inflammation due to implanted cotton pellets. Our results indicate also that hyper- and hypothyroid states can modify the response of the rat to some non-steroidal anti-inflammatory drugs.

Percutaneous absorption and anti-inflammatory activity of indomethacin in ointment

A jelly-type ointment containing 1% indomethacin, ID gel, was prepared, and the anti-infla-mmatory effects and percutaneous absorption of ID gel were studied. ID gel inhibited carrageenin-induced paw edema concentration-dependently by topical application and showed significant effect at concentratin over 1%. ID gel inhibited inflammation only in the applied foot, but did not influence the edema of non-applied foot in car-rrageenin-induced edema experiments. It was shown that percutaneous absorption of indomethacin was markedly more into the exudate and muscle of the applied foot than those of non-applied foot and systemic blood. ID gel showed also anti-inflam-matory erects on adjuvant arthritis in rats and ultraviolet-induced erythema in guinea pigs.

2-(5H-[1]Benzopyrano[2,3-b]pyridin-7-yl)propionic acid(Y-8004)の薬理学的研究（第III報）<SUP>a)</SUP> ―抗炎症薬との相互作用―

Interactions of Y-8004 with anti-inflammatory agents were examined in the carrageenin foot edema and adjuvant induced arthritis tests. The combined administration of hydrocortisone with Y-8004 or other acidic non-steroidal anti-inflammatory agents resulted in a synergistic inhibition of edema. The therapeutic effect of a combination of hydrocortisone and Y-8004 was found to be greater than the effect produced by each of the component agents at corresponding doses in the adjuvant induced arthritis test. Y-8004 also maintained the therapeutic effect of prednisolone by alternative administration in succession to prednisolone therapy as well as indomethacin. On the other hand, the combined effect of acetylsalicylic acid with Y-8004 was antagonistic at the combined ratio in 25 to 1, but synergistic at the combined ratio in 100 to 1. Similar results were obtained in combinations of Y-8004 and indomethacin. The acute toxicity of Y-8004 in rats was potentiated by the combined administration of hydrocortisone or acetylsalicylic acid. The toxicity of indomethacin was, however, antagonized by a combined administration with acetylsalicylic acid as well as the anti-inflammatory activity of indomethacin. These results suggest that Y-8004 may make feasible a reduction in dosage or a withdrawal of the steroid prescription. Antagonism between non-steroidal anti-inflammatory agents has yet to be established.

Prevention of antiinflammatory drug-induced gastric lesions in rats by Abbott-29590.

Abbott-29590, an antiinflammatory compound with antipyretic and analgesic activity in test animals, did not produce any gastric lesions in the rat after oral doses up to 256 mg/kg. In contrast, gastric lesions were produced by oral doses of aspirin, indomethacin, and phenylbutazone; the ED95 values were 88, 13, and 260 mg/kg, respectively. Pretreatment with Abbott-29590 blocked the gastric damage produced by aspirin and indomethacin but not the ulceration produced by phenylbutazone. The ED50 values of Abbott-29590 for preventing the gastric lesions produced by aspirin, Abbott-29590, and exogenous 0.1 N HCl suggest that Abbott-29590 was additive with aspirin in its antiinflammatory activity while simultaneously blocking the gastric lesions produced by aspirin. The antiinflammatory activity of indomethacin in the carrageenin rat paw edema test was not altered by 30 minutes pretreatment with Abbott-29590, while phenylbutazone and Abbott-29590 were additive in antiinflammattory activity. Studies of gastric lesions produced by a combination of aspirin, Abbott-29590, and exogenous 0.1N HCl suggest that Abbott-29590 may tighten the gastric mucosal barrier.