Cardiovascular outcomes in high risk patients with osteoarthritis treated with ibuprofen, naproxen or lumiracoxib

Farkouh, Michael E.; Greenberg, Jeffery; Jeger, Raban; Ramanathan, Krishnan; Verheugt, Freek W.A.; Chesebro, James H.; Kirshner, Howard S.; Hochman, Judith S.; Lay, Christine; Ruland, Sean; Mellein, B.; Matchaba, Patrice; Fuster, Valentín; Abramson, Steven B.

doi:10.1136/ard.2006.066001

Cited by 109 publications

(68 citation statements)

References 35 publications

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“…Ibuprofen, a nonsteroidal anti-inflammatory drug, has been widely used to treat pain, fever and inflammation due to its lower incidence of digestive [19,20] and renal adverseness [20,21,22] and cardiovascular risk [23,24] than most nonsteroidal anti-inflammatory drugs. It is a major medicine in the Essential Drugs List of the World Health Organization and available over the counter in most areas.…”

Section: Discussionmentioning

confidence: 99%

Ibuprofen Attenuates Cardiac Fibrosis in Streptozotocin-Induced Diabetic Rats

Qiao

Wang²,

Chen³

et al. 2015

Cardiology

136

114

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Objective: To investigate the effects of ibuprofen on cardiac fibrosis in a rat model of type 1 diabetes. Methods: The diabetic model was established by injecting streptozotocin into the rats. Then, ibuprofen or pioglitazone was given by gavage for 8 weeks. The cardiac fibrosis was assessed, and the major components of the renin-angiotensin system, the transforming growth factor β₁ (TGF-β₁) and the mammalian target of rapamycin (mTOR), were evaluated by histopathological, immunohistochemical, Western blot analysis or ELISA assay. Results: Obvious cardiac fibrosis was detected in the diabetic group and was alleviated by ibuprofen treatment. Angiotensin-converting enzyme (ACE), angiotensin (Ang) II and AngII type 1 receptor (AT1-R) levels were higher, and ACE2, Ang(1-7) and Mas receptor (Mas-R) were lower in the diabetic group. The ratio of ACE to ACE2 was raised in the diabetic group. All these changes were ameliorated by ibuprofen. TGF-β₁ and mTOR were raised in the hearts of the diabetic group and were attenuated by ibuprofen treatment. There was no significant difference between the ibuprofen and the pioglitazone groups. Conclusion: Ibuprofen could ameliorate the cardiac fibrosis in diabetic rats by reduction of the ACE/AngII/AT1-R axis and enhancement of the ACE2/Ang(1-7)/Mas-R axis, leading to a decrease in TGF-β₁ and mTOR.

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Section: Discussionmentioning

confidence: 99%

Ibuprofen Attenuates Cardiac Fibrosis in Streptozotocin-Induced Diabetic Rats

Qiao

Wang²,

Chen³

et al. 2015

Cardiology

136

114

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“…However, cyclooxygenase (COX)-2-specific drugs might be beneficial for adverse effects on cartilage. Recently observations have suggested that COX-2-specific drugs used at present also have their side effects and might increase the risk of cardiovascular diseases (20,21). Therefore, we need to develop novel drugs with which treatment for (osteo)arthritis is satisfactory for prolonged treatment of joint disease, including improvement of cartilage and inhibition of inflammation.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Effect of Siegesbeckia pubescens on Cartilage Protection in a Rabbit Collagenase-Induced Model of Osteoarthritis

et al. 2008

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Abstract. Siegesbeckia pubescens (S. pubescens) was widely used to alleviate symptoms of osteoarthritis (OA) in traditional medicine. However, the mechanism of action of S. pubescens remains unresolved. In the present study, we determined the physiological relevance of S. pubescens on cartilage protection in collagenase-induced osteoarthritis (CIA) in rabbits. The right knees of rabbits were injected intra-articularly with collagenase, and rabbits were orally administered with distilled water (vehicle), S. pubescens (100, 400 mg / kg) or celecoxib (100 mg / kg) once a day for 28 days after the initiation of the CIA. S. pubescens significantly suppressed the stiffness and global histological score including articular cartilage and synovial layer in CIA. Proteoglycan, aggrecan, and type II collagen expression was significantly increased in the rabbit knee joints of the S. pubescens-treated group. However, celecoxib had no effect on cartilage protection in CIA. The expression level of ADAMTS-4, ADAMTS-5, MMP-1, MMP-3, and MMP-13 were dose-dependently decreased in the S. pubescens-treated group. In contrast, the level of TIMP-1 dose-dependently increased. The pro-inflammatory cytokines involved in cartilage destruction, such as IL-1β, and inflammatory mediators containing PGE 2 and NO were also inhibited in the S. pubescens-treated group. These results indicate that the cartilage protective effect of S. pubescens works through down-regulation of inflammatory mediators and aggrecanases and MMPs, while up-regulating TIMP-1 in the CIA rabbit model.

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“…A number of drugs have been designed and applied depending on the affected organ, the status of the disease and the characteristics of the involved patient; however, the therapy can be expensive, and its effect may be symptomatic, non-permanent, and could cause collateral damage. For example, non-steroidal anti-inflammatory drugs can have adverse effects on bone tissue by modulating the proliferation, differentiation, adhesion, and migration of osteoblasts (Garcia-Martinez et al, 2015); some of the mentioned drugs, as well as aspirin, have been associated with upper gastrointestinal tract injury, including bleeding and ulcers (Goldstein, 2004;Goldstein and Crier, 2015), and they confer an increased risk for thrombotic and congestive heart failure (Farkouh et al, 2007). Furthermore, another risk factor to be considered is the concurrent use of anti-inflammatory drugs with other medications such as anticoagulants, corticosteroids, serotonin reuptake inhibitors or antihypertensive agents (Goldstein and Cryer, 2015;Kalafutova et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Anti-Inflammatory Capacity of Beta-Sitosterol in Rodent Assays

Paniagua-Pérez¹,

Flores-Mondragón²,

Reyes-Legorreta³

et al. 2016

AJTCAM

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Background: Beta-sitosterol (BS) is a compound discovered to be present in numerous plants. A number of interesting biomedical properties have been attributed to BS, including immuno-modulating and anti-inflammatory activities. Therefore, the aim of this report was to evaluate its anti-inflammatory capacity by applying various rodent experimental tests. Methods. To carry out the objective of the study we applied the methods indicated here. Two of the adopted methods were based on the passive reverse Arthus reaction: the rat paw edema test and the rat pleurisy assay. We also applied two methods related with the non-specific acute inflammation: the mouse ear edema test, and the mouse mieloperoxidase activity assay. Results. The results obtained in all tests established a significant anti-inflammatory potential of BS. In the rat paw edema test we found an inhibitory effect which goes from 50-70%; in the rat pleurisy assay our findings with respect to the volume of pleural exuded showed a reduction of 46%, as well as a 20% low amount of neutrophils in comparison with the level of the control group. In the mouse ear edema test we found a mean inflammatory inhibition of 75%, and with respect to mieloproxidase activity the results showed a significant inhibition induced by the three doses of BS. Conclusions. In the present study we determined a potent anti-inflammatory capacity of BS in specific and nonspecific types of acute inflammation in rodents.

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Cardiovascular outcomes in high risk patients with osteoarthritis treated with ibuprofen, naproxen or lumiracoxib

Cited by 109 publications

References 35 publications

Ibuprofen Attenuates Cardiac Fibrosis in Streptozotocin-Induced Diabetic Rats

Ibuprofen Attenuates Cardiac Fibrosis in Streptozotocin-Induced Diabetic Rats

Therapeutic Effect of Siegesbeckia pubescens on Cartilage Protection in a Rabbit Collagenase-Induced Model of Osteoarthritis

Evaluation of the Anti-Inflammatory Capacity of Beta-Sitosterol in Rodent Assays

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