Intra-articular orgotein in osteoarthritis of the knee: A placebo-controlled efficacy, Safety, and dosage comparison☆

McIlwain, Harris H.; Silverfield, Joel C.; Cheatum, Don E.; Poiley, Jeffrey; Taborn, James; Ignaczak, Thomas; Multz, Carter V.

doi:10.1016/0002-9343(89)90612-8

Cited by 3 publications

(4 citation statements)

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“…Interestingly, the first clinical pilot studies with the native enzyme were carried out as early as the 1970s in rheumatoid arthritis (RA) and osteoarthritis (OA), with preliminary results demonstrating efficacy. Further studies then showed that Orgotein®, when given by intra‐articular injection, attenuates signs and symptoms (inflammation and pain) of RA and OA ( Goebel et al , 1981 ; Goebel & Storck, 1983; Lund‐Olesen & Menander‐Huber, 1983; Gammer & Broback, 1984; Mc Ilwain et al , 1989 ; Mazieres et al , 1991 ). Interestingly, in these studies, Orgotein® led to some 60% decrease in the consumption of analgaesics.…”

Section: Discussionmentioning

confidence: 99%

“…When tested in humans in various clinical trials, Orgotein® (bovine CuZnSOD) showed promising results in acute and chronic conditions associated with inflammation, including rheumatoid arthritis and osteoarthritis ( Goebel et al , 1981 ; Goebel & Storck, 1983; Lund‐Olesen & Menander‐Huber, 1983; Gammer & Broback, 1984; Mc Ilwain et al , 1989 ; Mazieres et al , 1991 ; Borigini & Paulus, 1995) as well as side effects (acute and chronic) associated with chemotherapy and radiation therapy ( Marberger et al , 1974 ,1975,1981; Edsmyr et al , 1976 ; Menander‐Huber et al , 1978 ; Housset et al , 1989 ; Delanian et al , 1994 ; Sanchiz et al , 1996 ). Thus, in clinical trials, the use of the native enzyme supported the concept that removal of superoxide had a beneficial outcome.…”

Section: Sod: Clinical Experiencementioning

confidence: 99%

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On the selectivity of superoxide dismutase mimetics and its importance in pharmacological studies

Muscoli

Cuzzocrea

Riley³

et al. 2003

British J Pharmacology

246

225

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The list of pathophysiological conditions associated with the overproduction of superoxide expands every day. Much of the knowledge compiled on the role of this radical in disease has been gathered using the native superoxide dismutase enzyme and, more recently, by the use of superoxide dismutase knockout models or transgenic models that overexpress the various isoforms of the enzyme. Although the native enzyme has shown promising anti‐inflammatory properties in both preclinical and clinical studies, there were drawbacks and issues associated with its use as a therapeutic agent and pharmacological tool. Based on the concept that removal of superoxide modulates the course of inflammation, synthetic, low‐molecular‐weight mimetics of the superoxide dismutase enzymes that could overcome some of the limitations associated with the use of the native enzyme have been designed. In this review, we will discuss the advances made using various superoxide dismutase mimetics that led to the proposal that superoxide (and/or the product of its interaction with nitric oxide, peroxynitrite) is an important mediator of inflammation, and to the conclusion that superoxide dismutase mimetics can be utilized as therapeutic agents in diseases of various etiologies. The importance of the selectivity of such compounds in pharmacological studies will be discussed. British Journal of Pharmacology (2003) 140, 445–460. doi:

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Section: Discussionmentioning

confidence: 99%

Section: Sod: Clinical Experiencementioning

confidence: 99%

On the selectivity of superoxide dismutase mimetics and its importance in pharmacological studies

Muscoli

Cuzzocrea

Riley³

et al. 2003

British J Pharmacology

246

225

View full text Add to dashboard Cite

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“…Adjuvant antioxidant therapy is a promising approach for clinical management of periodontitis (Muniz et al 2015). While administering antioxidant enzymes such as superoxide dismutase has been proposed (Table 1), clinical trials in osteoarthritis have shown that intra-articular injections of SOD are not as efficacious as activation of NrF2 to inhibit oxidative stress and related pathophysiological states (McIlwain et al 1989). This is relevant in periodontitis because NrF2 activation affects the expression of hundreds of antioxidant gene products that are involved in protection against oxidants and free radicals (Table 3).…”

Section: Itoh Et Al 2003mentioning

confidence: 99%

The Role of NrF2 in the Regulation of Periodontal Health and Disease

et al. 2017

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Immune-related disease tolerance is an important defense strategy that facilitates the maintenance of health in organs and tissues that are commonly colonized by bacteria. Immune tolerance to dysbiotic, tooth-borne biofilms is a poorly understood yet clinically relevant concept in the immunopathological mechanisms that are involved in the pathogenesis of periodontitis, particularly those related to neutrophil and macrophage responses. In periodontal health, neutrophils and macrophages respond to the formation of pathogenic bacterial biofilms by the production of bactericidal reactive oxygen species (ROS). However, when released in excess, ROS cause tissue damage and exacerbate inflammation. To counter these destructive responses, many cell types, including neutrophils and macrophages, launch a dedicated antioxidant system that limits the cell and tissue-damaging effects of ROS. The expression of antioxidants is primarily regulated by genetic response elements in their promoters. Here we consider the roles of nuclear factor erythroid 2-related factor (NrF2), a transcription factor, and other key regulators of antioxidants. The concept of disease tolerance, neutrophil and macrophage-generated oxidative stress, and their relationship to the pathogenesis of periodontitis is reviewed. We focus on the regulation of NrF2 and recent evidence suggesting that NrF2 plays a central role in host protection against tissue destruction in periodontitis.

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“…Superoxide free‐radical ions can convert arachidonic acids to biologically active prostaglandins and mediate tissue injury and inflammation. Intraarticular injection of orgotein, a bovine Cu‐Zn superoxide dismutase, has been shown to reduce the symptoms of osteoarthritis 69 . These drugs represent a possibility for the future pharmaceutical treatment of osteoarthritis.…”

Section: Osteoarthritismentioning

confidence: 99%