Orgotein (superoxide dismutase): A drug for the amelioration of radiation-induced side effects

Menander-Huber, K B; Edsmyr, F; Huber, W.

doi:10.1007/bf00262630

Cited by 34 publications

(9 citation statements)

References 4 publications

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“…Furthermore, Orgotein® was found to be effective when given by intra‐articular injection in patients with temporomandibular joint (TMJ) dysfunction, who failed to respond to standard therapy ( Lin et al , 1994 ), and was found to reduce pain in patients with duodenal ulcer pain (Pascu & Dejica, 1987). Possibly, the most compelling data for the efficacy of SOD in human disease come from a large body of data gathered since the early 1980s, showing the protective effects of Orgotein® (given by intramuscular injection) against acute and chronic side effects 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 ). It is of major importance that Orgotein® is able to reverse fibrosis once it is established ( Niwa et al , 1985 ; Flohe, 1988).…”

Section: Discussionmentioning

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

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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%

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

show abstract

“…A large literature exists that has demonstrated delivery to or elaboration of superoxide dismutase (SOD), a detoxifying enzyme, in irradiated cells or tissues can reduce the deleterious effects of irradiation. Indeed, delivery of SOD and SOD modified to enhance delivery and stability have been successful in reducing the toxicity of radiation in clinical trials 9, 10 . Unfortunately, some studies have also failed to show a benefit and have reported allergic reactions 11 .…”

Section: Oxidative Stressmentioning

confidence: 99%

Mechanisms of Normal Tissue Injury From Irradiation

Citrin

Mitchell

2017

Seminars in Radiation Oncology

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Normal tissue injury from irradiation is an unfortunate consequence of radiotherapy. Technologic improvements have reduced the risk of normal tissue injury, however toxicity causing treatment breaks or long term side effects continue to occur in a subset of patients. The molecular events that lead to normal tissue injury are complex and span a variety of biologic processes, including oxidative stress, inflammation, depletion of injured cells, senescence, and elaboration of pro-inflammatory and pro-fibrogenic cytokines. This manuscript describes selected recent advances in normal tissue radiobiology.

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“…However, during radiation therapy, the overproduction of superoxide radicals so overwhelms native SOD enzymes that SO-mediated damage results, which suggest that exogenous administration of superoxide dismutase, will reduce the toxicity of radiation and chemotherapy. Indeed, during the 1970s, Orgotein, a Cu-Zn superoxide dismutase, was used successfully to ameliorate radiation-induced toxicity in bladder tumors [43] . However, use of SODs in the clinic has been limited by problems of immunogenicity when derived from non-human sources, large size (MW ~30,000) [44] and a short half-life, since they are prone to hydrolysis in vivo , and therefore require continuous infusion [45] .…”

Section: Gc4419mentioning

confidence: 99%

A Review of Clinical Radioprotection and Chemoprotection for Oral Mucositis

Oronsky¹,

Goyal

Kim

et al. 2018

Translational Oncology

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The first tenet of medicine, “primum non nocere” or “first, do no harm”, is not always compatible with oncological interventions e.g., chemotherapy, targeted therapy and radiation, since they commonly result in significant toxicities. One of the more frequent and serious treatment-induced toxicities is mucositis and particularly oral mucositis (OM) described as inflammation, atrophy and breakdown of the mucosa or lining of the oral cavity. The sequelae of oral mucositis (OM), which include pain, odynodysphagia, dysgeusia, decreased oral intake and systemic infection, frequently require treatment delays, interruptions and discontinuations that not only negatively impact quality of life but also tumor control and survivorship. One potential strategy to reduce or prevent the development of mucositis, for which no effective therapies exist only best supportive empirical care measures, is the administration of agents referred to as radioprotectors and/or chemoprotectors, which are intended to differentially protect normal but not malignant tissue from cytotoxicity. This limited-scope review briefly summarizes the incidence, pathogenesis, symptoms and impact on patients of OM as well as the background and mechanisms of four clinical stage radioprotectors/chemoprotectors, amifostine, palifermin, GC4419 and RRx-001, with the proven or theoretical potential to minimize the development of mucositis particularly in the treatment of head and neck cancers.

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Orgotein (superoxide dismutase): A drug for the amelioration of radiation-induced side effects

Cited by 34 publications

References 4 publications

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

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

Mechanisms of Normal Tissue Injury From Irradiation

A Review of Clinical Radioprotection and Chemoprotection for Oral Mucositis

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