A location of copper and zinc- superoxide dismutase (Cu, Zn-SOD) in adenohypophysis and pituitary adenomas was examined with immunohistochemical technique. The content of Cu, Zn-SOD was markedly higher in normal cells than adenoma cells.
Kurisaka-M; Nakajo-T; Mori-K: Immunohistochemical study on the expression of copper and zinc-superoxide dismutase (Cu, Zn-SOD) in human adenohypophysis and pituitary adenomas. No-To-Shinkei. 1994 Oct; 46(10): 948-54.
Over 15 years of research on correlations between superoxide dismutase (SOD) activity and aging or life span failed to provide a consistent picture. While genetic manipulations that increase CuZn-SOD activity have only a slight, if any, effect on maximum life span in several species, they do increase resistance to oxidative stress. However, increasing both CuZn-SOD and catalase does significantly increase maximum life span.
Warner-HR: Superoxide dismutase, aging, and degenerative disease.
Free-Radic-Biol-Med. 1994 Sep; 17(3): 249-58.
ALS (Superoxide Dismutase)
Mutation in superoxide dismutase 1 (SOD1), a Cu/Zn enzyme that removes oxygen radicals and protects against oxidative injury, has been implicated in some cases of familial amyotrophic lateral sclerosis (FALS). In this view, high, rather than limiting, levels of SOD1 may place motor neurons selectively at risk in FALS.
Pardo-CA; Xu-Z; Borchelt-DR; Price-DL; Sisodia-SS; Cleveland-DW: Superoxide dismutase is an abundant component in cell bodies, dendrites, and axons of motor neurons and in a subset of other neurons. Proc-Natl-Acad-Sci-U-S-A. 1995 Feb 14; 92(4): 954-8.
Cu/Zn superoxide dismutase (SOD)-like immunoreactivity (LI) was found within Lewy body-like inclusions (LBIs) in the spinal cords of patients with sporadic amyotrophic lateral sclerosis (ALS). Cu/ZnSOD appears to play roles in the production and/or degradation process of LBIs.
Komori-T; Ikemoto-A; Umahara-T; Shibata-N; Hirano-A; Kobayashi-M; Sasaki-S; Kato-T; Matsumoto-S; Shiozawa-Z. et-al: Cu/Zn superoxide dismutase-like immunoreactivity in Lewy body-like inclusions of sporadic amyotrophic lateral sclerosis. Neurosci-Lett. 1994 Sep 26; 179(1-2): 149-52.
Therapeutic trials for ALS have attracted much attention but no drug has been effective yet. Three major theories of pathogenesis form the basis for these trials: autoimmunity, chronic excitotoxic stimulation due to accumulation of glutamate, and, in the familial form, peroxidation due to subnormal activity of superoxide dismutase. Riluzole (a glutamate antagonist) benefited patients with bulbar onset but not those with spinal onset.
Rowland-LP: Amyotrophic lateral sclerosis. Curr-Opin-Neurol. 1994 Aug; 7(4): 310-5.
Alzheimer's disease may arise from or produce oxidative damage in the brain.
Assayed for glutathione, glucose-6-phosphate dehydrogenase, catalase and superoxide dismutase in twelve regions of Alzheimer's disease and aged control brains. The entire Alzheimer's brain may be subject to an oxidative challenge, but some areas may be more vulnerable than others to the consequent neural damage characteristic of the disease.
Balazs-L; Leon-M: Evidence of an oxidative challenge in the Alzheimer's brain. Neurochem-Res. 1994 Sep; 19(9): 1131-7.
"Oxidative stress" may be of significance in the etiopathogenesis of dementia of Alzheimer type (DAT). Measured activities of the enzymes superoxide dismutase (SOD) and catalase (CAT), which detoxicate reactive oxygen species. SOD activity increased with age in basal nucleus of Meynert. However, there was no significant difference in SOD activity between DAT and controls. There were significant reductions in CAT activity in parietotemporal cortex, basal ganglia, and amygdala in DAT compared with controls. Reactive oxygen species could contribute to the pathogenesis of DAT.
Gsell-W; Conrad-R; Hickethier-M; Sofic-E; Frolich-L; Wichart-I; Jellinger-K; Moll-G; Ransmayr-G; Beckmann-H; et-al: Decreased catalase activity but unchanged superoxide dismutase activity in brains of patients with dementia of Alzheimer type. J-Neurochem. 1995 Mar; 64(3): 1216-23.
Abnormalities in the cellular regulation and expression of antioxidant enzymes may have a role in mechanisms of central nervous system aging and neurodegeneration.
Examined the localization of copper/zinc-superoxide dismutase and manganese-superoxide dismutase in the frontal and temporal neocortices and hippocampi of aged controls and individuals with Alzheimer's disease or Down's syndrome in which the distributions and intensities of both forms of superoxide dismutase immunoreactivities were different from controls.
Copper/zinc-superoxide dismutase was enriched in pyramidal neurons undergoing degeneration, whereas manganese-superoxide dismutase was more enriched in reactive astrocytes than in neurons. In senile plaques, copper, zinc-superoxide dismutase-positive globular structures were surrounded by astrocytes highly enriched in manganese-superoxide dismutase. The observed changes in the cellular localization of superoxide dismutases in neocortex and hippocampus in these syndromes support a role for oxidative injury in neuronal degeneration and senile plaque formation.
This differential localization suggests that cellular responses to oxidative stress are specific and that various forms of superoxide dismutase have different functions in antioxidant mechanisms.
Furuta-A; Price-DL; Pardo-CA; Troncoso-JC; Xu-ZS; Taniguchi-N; Martin-LJ: Localization of superoxide dismutases in Alzheimer's disease and Down's syndrome neocortex and hippocampus. Am-J-Pathol. 1995 Feb; 146(2): 357-67.
Does oxidative stress occur in unstable angina? The concentrations of metallothionein and superoxide dismutase in plasma and in erythrocytes did not change in relation to the supplementation. The metallothionein concentration in both inflamed and non-inflamed intestinal mucosa was slightly higher after zinc supplementation but the superoxide dismutase concentration in the tissue was not altered.
Dubois-Rande-JL; Artigou-JY; Darmon-JY; Habbal-R; Manuel-C; Tayarani-I; Castaigne-A; Grosgogeat-Y: Oxidative stress in patients with unstable angina. Eur-Heart-J. 1994 Feb; 15(2): 179-83:
Reactive oxygen species (ROS) such as the superoxide (O2.-) and the hydroxyl radical (OH.) are aggressive chemical compounds that can induce tissue injury, e.g. by peroxidation of polyunsaturated fatty acids in cell membranes or directly by DNA damage. Many pathological conditions (e.g. ageing, cancer, stroke, hematologic disorders, adult respiratory distress syndrome (ARDS) and organ preservation in transplantation medicine) are in part caused by ROS.
There are various biological defense systems directed towards radicals: specific enzymes, e.g. superoxide dismutase or glutathione peroxidase; nonessential antioxidants, e.g. the plasma proteins and uric acid; and the essential antioxidants, e.g. vitamin C, vitamin E and carotenoids.
The chronic exposure of the organism to ROS is an important factor for tissue injury in the process of ageing. Lipofuscin is a typical product of lipid peroxidation and inversely correlates with longevity of an organism. The ingestion of higher doses of antioxidative vitamins is protective against cataracts.
The impairment of the immune system in elderly people might be prevented by a higher intake of multivitamin supplements. Whether supplementation with antioxidative vitamins can extend the life span in humans, as in experimental animals, remains unanswered.
Ballmer-PE; Reinhart-WH; Gey-KF: Antioxidant vitamins and disease--risk of a suboptimal supply. Ther-Umsch. 1994 Jul; 51(7): 467-74.
Fatty acid nitroxide radicals in CO-gassed erythrocytes are reduced by intracellular components with a half-life of about 160 min.
Catalase, glutathione, glutathione peroxidase, superoxide dismutase vitamin E and hemoglobin, individually or in concerted manner, contributed little in reducing membrane nitroxides. Ascorbic acid appeared to be the predominant component in the erythrocyte to reduce membrane nitroxides.
Zhang-Y; Fung-LW: The roles of ascorbic acid and other antioxidants in the erythrocyte in reducing membrane nitroxide radicals. Free-Radic-Biol-Med. 1994 Feb; 16(2): 215-22.
Reduced levels of glutathione peroxidase (GSH-Px) have been observed in adults with asthma. In children there were no significant differences in activity of SOD or vitamin C, retinol, or alpha tocopherol/cholesterol ratio. The reduction in GSH-Px activity may have therapeutic and etiological implications for asthma.
Powell-CV; Nash-AA; Powers-HJ; Primhak-RA: Antioxidant status in asthma. Pediatr-Pulmonol. 1994 Jul; 18(1): 34-8.
Simple bone cyst is a fluid-filled lesion that occurs in the metaphysis of the long bones of children and adolescents. Chemical are similar to serum. Blockage to the drainage of interstitial fluid within the metaphysis has been suggested as the primary cause of simple bone cyst thus causing an ischemic state in which oxygen free radicals are generated.
The precise measurement of free radical levels is difficult to obtain because of their extremely short half-lives. High levels of oxygen-free radicals induce high levels of oxygen scavengers locally to protect cells from the harmful effects of the free radicals. Therefore, the activity of the oxygen scavengers, superoxide dismutase and catalase, was measured as an indicator of high oxygen-free radical content in the cyst.
Komiya-S; Tsuzuki-K; Mangham-DC; Sugiyama-M; Inoue-A: Oxygen scavengers in simple bone cysts. Clin-Orthop. 1994 Nov(308): 199-206.
Distribution of manganese-dependent superoxide dismutase, an enzyme that transforms superoxide radicals into hydrogen peroxide, was studied post mortem. A heterogeneous distribution of manganese-dependent superoxide dismutase was observed. This heterogeneous but not ubiquitous distribution suggests that not all cells in the human brain are protected to the same extent against the deleterious effects of superoxide.
Zhang-P; Anglade-P; Hirsch-EC; Javoy-Agid-F; Agid-Y: Distribution of manganese-dependent superoxide dismutase in the human brain. Neuroscience. 1994 Jul; 61(2): 317-30.
Many anticancer drugs have been shown to produce superoxide anion (O2.-) and seem to involve O2.- in their mode of action. Ionizing radiation provokes the decomposition reaction of water, producing a variety of reactive oxygen species, including O2.-. The finding that cancer cells are generally low in SOD activity may offer a theoretical base for radiation therapy and chemotherapy.
Examines the protective effect of intracellular SOD against cytotoxicity induced by O2.- or radiation and to investigate whether exogenous SOD can protect cells from O2.-(-) and radiation-induced cytotoxicity.
Resistibilites O2.- and radiation correlated with intracellular Cu. Zn-SOD levels and that exogenous SOD could only slightly reduce X- and XOD-induced cytotoxicity while having no influence on radiation-induced cytotoxicity.
Thus, intracellular SOD may play a central role in protecting cancer cells against reactive oxygen species generated by anticancer drugs and radiation.
Yamaguchi-S; Sakurada-S; Nagumo-M: Role of intracellular SOD in protecting human leukemic and cancer cells against superoxide and radiation. Free-Radic-Biol-Med. 1994 Nov; 17(5): 389-95.
Cancer - Breast (Superoxide Dismutase)
Cancer - Breast
Analyzed products of lipid peroxidation reactions and activities of antioxidant enzymes in cancerous breast tissue and in corresponding reference tissue. In addition, the serum lipid peroxidation and peroxyl-radical-trapping capacity of breast cancer patients were compared to those of healthy subjects.
The activities of superoxide dismutase, glutathione peroxidase and the hexose monophosphate shunt were elevated. The antioxidant defense system is altered in cancerous breast tissues but the formation of lipid peroxides in the tumor tissue itself is not of primary importance in the carcinogenesis.
Punnonen-K; Ahotupa-M; Asaishi-K; Hyoty-M; Kudo-R; Punnonen-R: Antioxidant enzyme activities and oxidative stress in human breast cancer. J-Cancer-Res-Clin-Oncol. 1994; 120(6): 374-7.
Cancer - cervix
Cancer - cervix
Lipid peroxides, glutathione content and the activities of antioxidant enzymes were estimated in patients who had carcinoma of the uterine cervix and compared with normal. There was a remarkable reduction in glutathione content and in the activities of catalase and superoxide dismutase in neoplastic tissue in stages II, III and IV. These observations suggest impaired antioxidant status in carcinoma of the uterine cervix.
Balasubramaniyan-N; Subramanian-S; Govindasamy-S: Status of antioxidant systems in human carcinoma of uterine cervix. Cancer-Lett. 1994 Dec 9; 87(2): 187-92.
Cancer - Liver
Cancer - Liver
In hepatocellular carcinoma tissue the enzyme activities were all significantly lower than in control liver. Vitamin A was significantly decreased. Hepatocellular carcinoma develops in liver with severe impairment of cellular antioxidant systems, since, in patients with liver metastases from different cancers, despite low selenium concentrations, cellular scavenger enzymes have normal activities.
Casaril-M; Corso-F; Bassi-A; Capra-F; Gabrielli-GB; Stanzial-AM; Nicoli-N; Corrocher-R: Decreased activity of scavenger enzymes in human hepatocellular carcinoma, but not in liver metastases. Int-J-Clin-Lab-Res. 1994; 24(2): 94-7.
Cartilage (Superoxide Dismutase)
Interleukin-1 (IL-1) is a key mediator in the pathogenesis of cartilage destruction in arthritis-related disorders. Human recombinant superoxide dismutase (SOD) blocked IL-1-mediated cartilage destruction but had no effect on IL-1-mediated changes in glycosaminoglycan and prostaglandin E2 synthesis. These data suggest that superoxide anions may be one factor of IL-1-mediated cartilage destruction.
Fukuda-K; Dan-H; Saitoh-M; Takayama-M; Tanaka-S. Superoxide dismutase inhibits interleukin-1-induced degradation of human cartilage. Agents-Actions. 1994 Aug; 42(1-2): 71-3.
The diagnosis of a marginal copper deficiency has not been perfected. The specific activity of copper enzymes, or of copper-containing enzymes in blood cells, such as erythrocyte superoxide dismutase and platelet or leukocyte cytochrome c oxidase, may be a better indicator of metabolically active copper stores than the serum concentration of copper or ceruloplasmin.
Milne-DB: Assessment of copper nutritional status. Clin-Chem. 1994 Aug; 40(8): 1479-84.
Diabetes (Superoxide Dismutase)
Vascular complications such as atheroma, hypertension and macroangiopathy are the leading causes of morbidity and mortality in diabetic patients. These effects of hyperglycaemia are reversed by a number of antioxidants, including superoxide dismutase, catalase and glutathione. The evidence for a role of oxygen-derived free radicals in the pathogenesis of vascular diabetic complications can be summarized as follows:
1) glucose can auto-oxidize generating oxygen derived free radicals;
2) elevated levels of oxygen derived free radicals are found in red blood cells, plasma and retina of diabetic animals and patients, and correlate with metabolic control;
3) endogenous antioxidants are all decreased in diabetic tissues and blood; and
4) treatment with different antioxidants may improve many of the metabolic abnormalities reported to occur in diabetic patients. The use of antioxidants to reduce the risk of coronary heart disease in diabetes should await the results of randomized trials with these drugs in the primary and secondary prevention of coronary disease.
Giugliano-D; Acampora-R; D'Onofrio-F: Medical hypothesis: cardiovascular complications of diabetes mellitus-from glucose to insulin and back. Diabete-Metab. 1994 Sep-Oct; 20(5): 445-53.
The aim of the study was to evaluate the concentration of malondialdehyde (MDA) end product of lipid peroxidation, activity of antioxidant enzymes: superoxide dismutase (CuZn-SOD), glutathione peroxidase (GSH-Px), and catalase (Cat) as well as selenium (Se), zinc (Zn) and copper (Cu) concentration in erythrocytes.
Increased lipid peroxidation and the lack of compensatory mechanisms - an increase in antioxidant enzymes activity as well as disorder of trace elements concentration - are found in pregnant type I diabetics.
Twardowska-Saucha-K; Grzeszczak-W; Lacka-B; Froehlich-J; Krywult-D: Lipid peroxidation, antioxidant enzyme activity and trace element concentration in II and III trimester of pregnancy in pregnant women with diabetes. Pol-Arch-Med-Wewn. 1994 Oct; 92(4): 313-21.
Antibodies directed against MnSOD (the autoantigen P26) were detected in sera from 32 patients with acute Epstein-Barr virus (EBV) infection and clinical symptoms of infectious mononucleosis. They are not detectable in sera of patients with other herpes virus infections. The rise and fall of the autoantibodies coincides with the clinical symptoms. In vitro, the autoantibodies were shown to inhibit the dismutation of superoxide radicals by blocking MnSOD. This effect may contribute to the pathogenesis of acute EBV infection.
Ritter-K; Kuhl-RJ; Semrau-F; Eiffert-H; Kratzin-HD; Thomssen-R: Manganese superoxide dismutase as a target of autoantibodies in acute Epstein-Barr virus infection. J-Exp-Med. 1994 Nov 1; 180(5): 1995-8.
Influenza infections cause airway epithelial inflammation and oxidant-mediated damage. In this setting, cellular antioxidant enzymes may protect airway epithelial cells against damage resulting from toxic oxygen radicals produced by activated leukocytes.
Tested the effect of influenza virus infection on gene expression for the antioxidant enzymes manganese superoxide dismutase (MnSOD), copper/zinc superoxide dismutase (Cu/ZnSOD), indoleamine 2,3-dioxygenase (IDO), and catalase in primary cultures of human airway epithelial cells.
MnSOD increased, Cu/ZnSOD gene expression was unaffected. The differential effects of viral infection on antioxidant gene expression are likely to be important protective mechanisms in viral airway infections.
Jacoby-DB; Choi-AM: Influenza virus induces
A significant increase of SOD activity was observed in samples from superficial gastritis and only insignificant changes in samples from atrophic gastritis, while a remarkable and significant increase in the activity of both SOD and CAT was observed in samples from gastritis after partial gastrectomy. Application of vitamin E significantly reduced activities of SOD and CAT in subjects with chronic gastritis
Beno-I; Volkovova-K; Staruchova-M; Koszeghyova-L: The activity of Cu/Zn-superoxide dismutase and catalase of gastric mucosa in chronic gastritis, and the effect of alpha-tocopherol. Bratisl-Lek-Listy. 1994 Jan; 95(1): 9-14.
Adenosine deaminase (ADA), 5'-Nucleotidase (5NT), Xanthine oxidase (XO), Cu-Zn Superoxide dismutase (SOD) and Catalase (CAT) activities were determined in gastric juices from patients with gastric cancer, ulcer, gastritis and from healthy subjects. There was no significant difference between Cu-Zn SOD activities of the cancer and control groups.
In the ulcer group, we found higher Cu-Zn SOD and XO activities.
Durak-I; Ormeci-N; Akyol-O; Canbolat-O; Kavutcu-M; Bulbul-M: Adenosine deaminase, 5'-nucleotidase, xanthine oxidase, superoxide dismutase, and catalase activities in gastric juices from patients with gastric cancer, ulcer, and atrophic gastritis. Dig-Dis-Sci. 1994 Apr; 39(4): 721-8.
The primary defense against oxidation damage of tissues are anti-oxidant enzymes, e.g. superoxide dismutase, catalase and glutathione peroxidase. Some non-enzymatic substances have a significant anti-oxidant action (e.g. vitamin C, E, beta-carotene and others)..
The increased activity of anti-oxidant enzymes (in subjects with the risk of developing gastric cancer, e.g. those suffering from atrophic gastritis, hyperplastic polyps and gastric adenoma) was due to a higher concentration of the superoxide anion radical, hydrogen peroxide and organic peroxides (lipoperoxides); the source of active types of oxygen are phagocytic leucocytes in the chronically inflamed gastric mucosa.
Beno-I; Batovsky-M; Volkovova-K; Staruchova-M: Antioxidant enzyme activity in the gastric mucosa in precancerous conditions. Cas-Lek-Cesk. 1994 Feb 28; 133(5): 144-6.
Headache (Superoxide Dismutase)
Superoxide dismutase (SOD) is a radical-scavenging enzyme. We determined Cu, Zn-SOD concentrations and activities in platelets from subjects with migraine and tension-type headaches. It is suggested that low platelet SOD levels may play an important role in the etiology of migraine.
Shimomura-T; Kowa-H; Nakano-T; Kitano-A; Marukawa-H; Urakami-K; Takahashi-K: Platelet superoxide dismutase in migraine and tension-type headache. Cephalalgia. 1994 Jun; 14(3): 215-8; discussion 181.
Reactive oxygen species (ROS) have been implicated in the pathogenesis of pregnancy-induced hypertension (PIH). A genetic factor is also thought to be associated with the disease. The results showed that SOD activity was significantly reduced in patients with PIH. Suggest decreased SOD levels in PIH are not due to abnormalities in the CuZn-SOD gene but are acquired occurs during the development of the disease.
Chen-G; Wilson-R; Boyd-P; Mckillop-JH; Leitch-C; Walker-JJ; Burdon-RH: Normal superoxide dismutase (SOD) gene in pregnancy-induced hypertension: is the released SOD activity a secondary phenomenon? Free-Radic-Res. 1994 Aug; 21(2): 59-66.
Iron & Superoxide Dismutase
Iron deficiency is an important nutritional problem in third world countries because it diminishes work performance. In meat-eating countries, iron excess may be more important than iron deficiency. Iron excess can produce cellular oxidation in association with superoxide dismutase. Metal ion catalysis is linked to aging, coronary artery disease, stroke, carcinogenesis, neurodegenerative disorders, and inflammatory disorders. Prudence is advised in the excessive consumption of meat and iron supplementation of the diet until this process is more thoroughly investigated.
Conrad-ME; Uzel-C; Berry-M; Latour-L: Ironic catastrophes: one's food--another's poison. Am-J-Med-Sci. 1994 Jun; 307(6): 434-7.
Ischemic heart disease
Ischemic heart disease
Evaluate the oxygen free radical system in 29 patients with acute and chronic myocardial ischemic syndromes compared with 9 controls. Parameters assessed for oxidative stress were superoxide anion and malonyldialdehyde; and for the antioxidant defence system: superoxide dismutase, catalase and glutathione reductase.
In myocardial ischemia both oxidative stress and the antioxidant defence system were altered. In unstable angina and acute myocardial infarction, superoxide anion, malonyldialdehyde and glutathione reductase were elevated while superoxide dismutase and catalase levels were reduced. In stable angina only increased levels of superoxide anion and decreased levels of superoxide dismutase were found. However, this alteration was less marked than in unstable angina and acute myocardial infarction. In the post myocardial infarction group there was no alteration in any of these parameters.
Chandra-M; Chandra-N; Agrawal-R; Kumar-A; Ghatak-A; Pandey-VC: The free radical system in ischemic heart disease. Int-J-Cardiol. 1994 Feb; 43(2): 121-5.
Low-density lipoproteins (LDL) oxidized by oxygen radicals are a potent atherogenic stimulus. Chemically modified LDL are internalized by macrophages via a specific cell surface receptor ("the scavenger receptor") and can induce foam cell transformation. Post-translational nonenzymatic glycosylation of low density lipoprotein (LDL) occurs in vivo in diabetic patients. Glycosylated LDL (glcLDL) is degraded by macrophages in part by the classic LDL-receptor and in part by the scavenger receptor. This latter mechanism may contribute to the formation of foam cells and acceleration of atherosclerosis in diabetes mellitus.
A free radical is any chemical species that has an unpaired electron. This property renders it highly chemically reactive. When a radical reacts with a non radical another free radical is generated. This characteristic enables radicals to trigger chain reactions. Oxygen radicals are: superoxide anion (.O2-), hydroxyl radical (.OH) and hydrogen peroxide (H2O2).
Napoli-C; Ambrosio-G; Aalumbo-G; Chiariello-P; Duilio-C; Chiariello-M: The peroxidation of human glycosylated low-density lipoproteins is mediated by the superoxide radical: the protective effects of superoxide dismutase. Cardiologia. 1994 May; 39(5): 345-52.
62 hyperlipemic patients were divided into 2 groups, half treated with Chinese herbal medicine Jiangzhi Zhongyao Pian (JZZYP) or placebo. Serum lipid, RBC-superoxide dismutase (RBC-SOD) and malondialdehyde (MDA) were observed. Total cholesterol (TC), triglyceride (TG), atherogenic index (AI) and (MDA) of the test group were apparently dropped and high density lipid-cholesterol (HDL-C), RBC-SOD activity obviously elevated after treatment. JZZYP regulated serum lipid, antioxidase activity elevation and lipid peroxide inhibition without side effects.
Liang-XC: Effect of jiangzhi zhongyao pian on serum lipid and antioxidation of hyperlipemic patients. Chung-Kuo-Chung-Hsi-I-Chieh-Ho-Tsa-Chih. 1994 Mar; 14(3): 139-41, 131.
Method of action
Method of action
To clarify whether lecithinized superoxide dismutase (PC-SOD) enhanced its pharmacologic potency by increasing its cell membrane affinity.
PC-SOD, in which 4 molecules of a phosphatidylcholine (PC) derivative were covalently bound to each dimer of recombinant human CuZn-SOD (rhCuZn-SOD). PC-SOD was approximately 100-fold more potent than unmodified SOD. These results suggest that PC-SOD exerted a far higher pharmacologic effect and may be useful for various clinical applications.
Igarashi-R; Hoshino-J; Ochiai-A; Morizawa-Y; Mizushima-Y: Lecithinized superoxide dismutase enhances its pharmacologic potency by increasing its cell membrane affinity. J-Pharmacol-Exp-Ther. 1994 Dec; 271(3): 1672-7.
Extracellular-superoxide dismutase (EC-SOD), a secretory glycoprotein, is the major SOD isozyme in extracellular fluids. EC-SOD levels in sera from healthy persons are clearly divided into two discontinuous groups: a lower group (named Group I, below 120 ng/ml) and a higher group (Group II, above 400 ng/ml). The family studies have shown that the high EC-SOD level in healthy persons is genetically transmitted.
EC-SOD levels were distinctly higher in patients with renal diseases and moderately higher in liver diseases and diabetes than normal. In cerebrovascular diseases, heart and acute digestive diseases, significant differences of EC-SOD were not observed. In patients with renal diseases, the increase of EC-SOD was accompanied by the lack of renal function.
Adachi-T; Nakamura-M; Yamada-H; Futenma-A; kato-K; Hirano-K: Quantitative and qualitative changes of extracellular-superoxide dismutase in patients with various diseases. Clin-Chim-Acta. 1994 Sep; 229(1-2): 123-31.
Motor Neurone Disease
Motor Neurone Disease
The cause of motor neuron disease (MND) remains unknown. Current concepts link neurotransmitters [excitatory amino acids (EAAs)] and free radical induced neuronal damage; especially following reports of mutations in the gene encoding the free radical scavenging enzyme, copper-zinc superoxide dismutase, in familial MND.
Zeman-S; Lloyd-C; Meldrum-B; Leigh-PN : Excitatory amino acids, free radicals and the pathogenesis of motor neuron disease. Neuropathol-Appl-Neurobiol. 1994 Jun; 20(3): 219-31.
Significant oxidative mechanisms involve the activity of monoamine oxidase (MAO) and the formation of free radicals, in the pathogenesis of Parkinson's disease.
Conclusive clinical evidence of a neuroprotective effect in PD is still lacking. Possible mechanisms by which selegiline manifests neuroprotective effects includes the induction of superoxide dismutase. Besides MAO-B inhibition, selegiline appears to exhibit other mechanisms of action stimulation of neurotrophic factor synthesis and antagonistic modulation of the polyamine binding site of the NMDA.
Gerlach-M; Youdim-MB; Riederer-P: Is selegiline neuroprotective in Parkinson's disease? J-Neural-Transm-Suppl. 1994; 41: 177-88.
A clinical trial using Cu/Zn superoxide dismutase (Lipsod) to treat long-standing (RIF).
Lipsod was administered over 3 weeks in twice weekly i.m. injections of 5 mg for a total of 30 mg. All patients showed some clinical regression (30%) of fibrosis. In most patients, clinically assessable regression begun during the third week of treatment and was maximum by 2 months.
Delanian-S; Baillet-F; Huart-J; Lefaix-JL; Maulard-C; Housset-M: Successful treatment of radiation-induced fibrosis (RIF) using liposomal Cu/Zn superoxide dismutase: clinical trial. Radiother-Oncol. 1994 Jul; 32(1): 12-20.
Measured enzymic and non-enzymic antioxidants in human epidermis and dermis from 6 healthy volunteers undergoing surgical procedures. Among the enzymic antioxidants, the activities of superoxide dismutase, glutathione peroxidase, and glutathione reductase were higher in the epidermis compared to the dermis by 126, 61 and 215%, respectively. Thus the antioxidant capacity of the human epidermis is far greater than that of dermis. (Not surprising, as the epidermis composes the outermost 10% of the skin, providing the initial barrier to oxidant assault.)
Shindo-Y; Witt-E; Han-D; Epstein-W; Packer-L: Enzymic and non-enzymic antioxidants in epidermis and dermis of human skin. J-Invest-Dermatol. 1994 Jan; 102(1): 122-4.
Superoxide dismutase (SOD), neuron specific enolase (NSE) and lactic dehydrogenase (LDH) were measured in the serum and cerebrospinal fluid (CSF) of ischemic cerebrovascular patients, other neurological patients and in -matched controls (serum only).
The levels of SOD in the CSF or serum of the ischemic patients in the first 24 hrs after stroke were similar to the control groups. However, SOD levels in the ischemic patients increased, suggesting that oxygen radicals are formed and the increased synthesis of SOD protects the patients from potential damage.
Gruener-N; Gross-B; Gozlan-O; Barak-M: Increase in superoxide dismutase after cerebrovascular accident. Life-Sci. 1994; 54(11): 711-3.
Patients with active vitiligo (AVP) have elevated urinary levels of catecholamine metabolites, such as homovanillic and vanilmandelic. Abnormal release of catecholamines from autonomic nerve endings might play an etiological role in the onset and development of vitiligo through an overproduction of toxic (oxy)radicals in the microenvironment of melanocytes in the affected areas. The present study investigated whether this increase in radicals is associated with an oxidative stress in the blood of AVP.
Blood levels of Vit E, SOD, GSH etc. were not significantly different from controls, indicating that AVP is not linked with oxidative stress.
Picardo-M; Passi-S; Morrone-A; Grandinetti-M; Di-Carlo-A; Ippolito-F: Antioxidant status in the blood of patients with active vitiligo. Pigment-Cell-Res. 1994 Apr; 7(2): 110-5.
The purpose of this study was to examine the effects of ethanol, type of dietary carbohydrate (fructose vs. starch), and levels of dietary copper (deficient vs. adequate) on antioxidant defense mechanism in the female rat.
As expected, copper deficiency dramatically reduced SOD.
Data show that copper deficiency, per se, and the combination of copper deficiency with fructose feeding lower the antioxidant defense system in female rats.
Antioxidant defense mechanisms in the female rat: interactions with alcohol, copper, and type of dietary carbohydrate. Fields-M; Lewis-CG. Alcohol. 1995 May-Jun; 12(3): 227-31.
In a parallel study using male rats, the following conclusion was drawn:
Data suggest that additional mechanisms to antioxidant defense systems are responsible for the metabolic changes that occur during the interactions between ethanol low copper and dietary carbohydrates.
Antioxidant defense mechanisms in the male rat: interaction with alcohol, copper, and type of dietary carbohydrate. Fields-M; Lure-MD; Lewis-CG. Alcohol. 1995 Jan-Feb; 12(1): 65-70.
Cardiac ultrastructure (Rat)
Cardiac ultrastructure (Rat)
To determine if chronic ingestion of a diet containing a marginally low level of Cu could cause deleterious alterations in cardiac ultrastructure
Suggests that abnormalities in cardiac ultrastructure occurred in rats chronically fed diets marginally low in Cu, despite minimal changes in conventional biochemical indicators of Cu status.
Marginal copper-restricted diets produce altered cardiac ultrastructure in the rat. Wildman-RE; Hopkins-R; Failla-ML; Medeiros-DM. Proc-Soc-Exp-Biol-Med. 1995 Oct; 210(1): 43-9.
Low carotene diet (SOD)
Low carotene diet
The effect of consuming a low carotene diet (approximately 60 micrograms carotene/day) on oxidative susceptibility and superoxide dismutase (SOD) activity in women living in a metabolic research unit was evaluated.
Erythrocyte SOD activity was depressed in carotene-depleted women; it recovered with repletion.
Dietary carotene seems to be needed, not only as a precursor of vitamin A, but also to inhibit oxidative damage and decrease oxidation susceptibility.
Effects of a carotene-deficient diet on measures of oxidative susceptibility and superoxide dismutase activity in adult women. Dixon-ZR; Burri-BJ; Clifford-A; Frankel-EN; Schneeman-BO; Parks-E; Keim-NL; Barbieri-T; Wu-MM; Fong-AK; et-al. Free-Radic-Biol-Med. 1994 Dec; 17(6): 537-44.
Superoxide dismutase (SOD) may aid in the removal of O2- and peroxynitrite from areas of duodenal and intestinal injury, thereby aiding in the treatment of septic shock or the conditions of gastrointestinal inflammation, according to this study conducted on rats. The researchers injected rats with E.coli lipopolysaccharide (LPS), which elicited an inflammatory response that was characterized by a time-dependent infiltration of neutrophils, lipid peroxidation, microvascular leakage (indicative of microvascular damage), and epithelial cell injury in both the duodenum and jejunum. Administration of SOD reduced these inflammatory effects of LPS.
Salvemini D, Riley DP, Lennon PJ, Wang ZQ, Currie MG, Macarthur H, Misko TP: Protective effects of a superoxide dismutase mimetic and peroxynitrite decomposition catalysts in endotoxin-induced intestinal damage, Br J Pharmacol 1999 Jun;127(3):685-92
Amytrophic Lateral Sclerosis
Amytrophic lateral sclerosis
Familial amyotrophic lateral sclerosis (FALS) may be caused, in part, by mutations in superoxide dismutase 1 (SOD1) polypeptides, according to this study conducted in vitro on nine different FALS variants. Each of these variants were found to be soluble, but exhibited vast differences in activity, polypeptide half-life, and resistance to proteolysis. The researchers conclude that different life expectancies of FALS patients may be due to an unidentified property of these mutant enzymes.
Ratovitski T, Corson LB, Strain J, Wong P, Cleveland DW, Culotta VC, Borchelt DR: Variation in the biochemical/biophysical properties of mutant superoxide dismutase 1 enzymes and the rate of disease progression in familial amyotrophic lateral sclerosis kindreds, Hum Mol Genet 1999 Aug;8(8):1451-1460
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