Superoxide Dismutase Mimetic Activity Research Articles

Attenuation of Aβ‐Induced Apoptosis of Plant Extract (Saengshik) Mediated by the Inhibition of Mitochondrial Dysfunction and Antioxidative Effect

Recently, considerable attention has been focused on dietary manipulation of oxidative and/or nitrosative damage on neuronal cells. In this article, a neuroprotective effect of plant (Saengshik) extracts was investigated. Rat pheochromocytoma (PC12), cells treated with beta-amyloid underwent apoptotic death as determined by positive in situ terminal end-labeling (TUNEL staining), decreased mitochondrial transmembrane potential, and elevated caspase-3 activity co-occurring with enhanced MDA accumulation and the reduction of GSH levels. Saengshik pretreatment attenuated beta-amyloid-induced apoptosis in PC12 cells possibly by inhibiting mitochondrial dysfunction and exerting antioxidant properties. Saengshik pretreatment inhibited the loss of mitochondrial membrane potentials and reduced the activation of caspase-3. The in vitro antioxidant activities of Saengshik extracts were verified by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method and superoxide dismutase (SOD) mimetic activity. In beta-amyloid-challenged PC12 cells, Saengshik prevented the production of ROS, decreased the level of MDA, and elevated GSH. The potential of Saengshik as one of the neuroprotective regimens has been suggested through this article, and the combination with defined pharmaceuticals or other dietary antioxidants may provide a better therapeutic or preventive advantage for the management of Alzheimer's disease.

Acute antihypertensive response to tempol in the SHR depends on ATP‐sensitive potassium channel (K ATP ), but not large‐conductance Ca2+‐activated potassium (BK) channels

Acute intravenous (IV) administrations of the piperidine nitroxides reduce BP and heart rate (HR) in SHR in proportion to their superoxide dismutase (SOD) mimetic activity. Blockade of nitric oxide synthase (NOS) blunted 40% of the fall in MAP with IV tempol whereas blockade of ganglionic sympathetic neurotransmission with hexamethonium blunted 40% of the fall in MAP, and combined blockade blunted about 80% of the fall in BP. Central administration of tempol was ineffective. Here, we tested the hypothesis that the tempol activates potassium conductances in vivo. Tempol caused dose-dependent reductions in MAP and HR maximal at 174 μmol/kg (ΔMAP −56 ± 4 mmHg and ΔHR −34 ± 5 min−1, n=7). Activation of KATP channel with cromakalim (50 μg iv bolus and 50 μg /hr, iv), with coinfusion of norepinephrine to restore BP toward control level significantly reduced tempol antihypertensive response by 40% (at 174 μmol/kg, ΔMAP −33 ± 5 mmHg, p < 0.01), whereas blockade of KATP channels with glibenclamide (15 mg/kg) significantly reduced tempol antihypertensive response by 31% (ΔMAP −46 ± 10 vs. control −67 ± 8 mmHg, n=6; p<0.01). In contrast, inhibition of BK channels with iberiotoxin (100 and 300 μg/kg, n=6) did not affect tempol’s antihypertensive effect. In conclusion, the acute antihypertensive response to IV tempol is mediated via potentiation of NO, reduction in sympathetic tone and activation of KATP, but not BK channels.

Effect of the reduction of superoxide dismutase 1 and 2 or treatment with α-tocopherol on tumorigenesis in Atm-deficient mice

Atm-deficient mice, a cancer-prone model of the human disease ataxia-telangiectasia, display increased levels of oxidative stress and damage. Chronic treatment of these mice with the nitroxide antioxidant and superoxide dismutase (SOD) mimetic Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine- N-oxyl) resulted in an increased latency to tumorigenesis. We initially hypothesized that the chemopreventative effect of Tempol was due to its SOD mimetic activity reducing cellular oxidative stress and damage. However, it is also possible that the chemopreventative effect of Tempol results from mechanisms other than directly reducing superoxide radical-induced oxidative stress and damage. To help distinguish between these possibilities, we attempted to genetically increase oxidative stress in Atm-deficient mice by either removing cytosolic Sod1 or reducing mitochondrial Sod2, or we attempted to decrease oxidative stress by treatment of Atm-deficient mice with α-tocopherol. Surprisingly, we found that reducing both Atm and Sod1 or Atm and Sod2 did not shorten latency to tumorigenesis or significantly affect life span. Furthermore, continuous administration of α-tocopherol did not affect latency to thymic lymphomas. Thus, genetically reducing Sod in Atm-deficient mice or treatment with α-tocopherol had no effect on survival or tumorigenesis, suggesting that the chemopreventative effect of Tempol may be at least partially independent of its effects on reducing oxidative damage and stress.

The Magnetic Resonance Imaging Contrast Agent Mangafodipir Exerts Antitumor Activity via a Previously Described Superoxide Dismutase Mimetic Activity

To the Editor: It was recently described in Cancer Research by Laurent et al. ( [1][1]) how low molecular weight superoxide dismutase (SOD) mimetics increase H2O2 levels, which in turn killed colon (CT26) and liver (Hepa 1-6) tumor cells. In contrast, the SOD mimetics stimulated proliferation of

Synthesis, Superoxide Dismutase Mimetic and Anticancer Activities of Metal Complexes of 2,2-Dimethylpentanedioic Acid(2dmepdaH(2)) and 3,3-Dimethylpentanedioic acid(3dmepdaH(2)): X-Ray Crystal Structures of [Cu(3dmepda)(bipy)](2). 6H(2)O and [Cu(2dmepda)(bipy)(EtOH)](2). 4EtOH (bipy = 2,2'Bipyridine).

2,2-dimethylpentanedioic acid (2dmepdaH2) and 3,3-dimethylpentanedioic acid (3dmepdaH2) reacted with copper(II) acetate to give [Cu(2dmepda)(H2O)3]2 (1) and [Cu(3dmepda)(H2O)3]2 (2). Reaction of (1) and (2) with 1,10-phenanthroline and 2,2′-bipyridine yielded [Cu(2dmepda)(phen)(H2O)]20.5phen (3), [Cu(2dmepda)(bipy)(H2O)]2 (4), [Cu(2dmepda)(bipy)(EtOH)]2· 2EtOH (4A), [Cu(3dmepda)(phen)(H2O)]2 (5), and [Cu(3dmepda)(bipy)(H2O)]2· (6). The structures of (4A) and (6) each consists of a [Cu(bipy)(dicarboxylate)(solvent)]2 dimer. The superoxide dismutase (SOD) mimetic activity of the novel copper complexes and their manganese analogues was investigated. The dimethyl sulphoxide(DMSO) soluble complexes (1)–(4) and (6) were assessed for their cancer chemotherapeutic potential towards hepatocellular carcinoma and kidney adenocarcinoma cell lines. The 1,10-phenanthroline containing complex [Cu(2dmepda)(phen)(H2O)]20.5phen (3) was the most potent with activity that compares well to that of cisplatin.

Orally active antioxidative copper(II) aspirinate: synthesis, structure characterization, superoxide scavenging activity, and in vitro and in vivo antioxidative evaluations

Ever since it was proposed that reactive oxygen species (ROS) are involved in the pathogeneses of various diseases, superoxide dismutase (SOD)-mimetic complexes have been intensively studied. We prepared copper(II) aspirinate [Cu2(asp)4] from Cu(II) and aspirin, which has been in use for many years as an antipyretic, an analgesic, and an anti-inflammatory agent. However, Cu2(asp)4 has been found to have additional activities, including anti-inflammatory, antiulcer, anti-ischemic/reperfusion agent, anticancer, antimutagenic, and antimicrobial activities. The activity of copper salicylate [Cu(sal)2] was also compared with that of Cu2(asp)4. The structure of the Cu2(asp)4 was determined using X-ray structure analysis. Its SOD-mimetic activity was determined using cytochrome c, electron spin resonance (ESR) spectroscopy, and ESR spin trap methods. The activity of Cu2(asp)4 was slightly greater than CuSO4 and copper acetate [Cu(ace)2] and slightly less than that of Cu(sal)2. The in vitro antioxidant activity, evaluated in human epithelial or transformed neoplastic keratinocyte cells, HaCaT, and normal dermal fibroblasts in terms of cell survival following ultraviolet B (UVB) irradiation, was significantly increased in the presence of Cu2(asp)4, Cu(sal)2, and CuSO4. Further, ROS generation following UVA irradiation in the skin of hairless mice following oral treatment with Cu2(asp)4 for three consecutive days was significantly suppressed compared to the vehicle- or Cu(ace)2-treated mice. On the basis of these results, Cu2(asp)4 was observed to be a potent antioxidative compound possessing antioxidative activity in biological systems. In conclusion, Cu2(asp)4 is a potent antioxidative agent that may be useful for future treatment of diseases resulting from ROS.

Acute antihypertensive action of nitroxides in the spontaneously hypertensive rat

Tempol is an amphipathic radical nitroxide (N) that acutely reduces blood pressure (BP) and heart rate (HR) in the spontaneously hypertensive rat (SHR). We investigated the hypothesis that the response to nitroxides is determined by SOD mimetic activity or lipophilicity. Groups (n = 6-10) of anesthetized SHRs received graded intravenous doses of Ns: tempol (T), 4-amino-tempo (AT), 4-oxo-tempo (OT), 4-trimethylammonium-2,2,6,6-tetramethylpiperidine-1-oxyl iodide (CAT-1), 3-carbamoyl-proxyl (3-CP), or 3-carboxy-proxyl (3-CTPY). Others received native or liposomal (L) Cu/Zn SOD. T and OT are uncharged, AT is positively charged and cell-permeable, and CAT-1 is positively charged and cell-impermeable. 3-CP and 3-CTPY have five-member pyrrolidine rings, whereas T, AT, OT, and CAT-1 have six-member piperidine rings. T and AT reduced mean arterial pressure (MAP) similarly (-48 +/- 2 mmHg and -55 +/- 8 mmHg) but more (P < 0.05) than OT and CAT-1. 3-CP and 3-CTPY were ineffective. The group mean change in MAP with piperidine Ns correlated with SOD activity (r = -0.94), whereas their ED(50) correlated with lipophilicity (r = 0.89). SOD and L-SOD did not lower BP acutely but reduced it after 90 min (-32 +/- 5 and -31 +/- 6 mmHg; P < 0.05 vs. vehicle). Pyrrolidine nitroxides are ineffective antihypertensive agents. The antihypertensive response to piperidine Ns is predicted by SOD mimetic action, and the sensitivity of response is by hydrophilicity. SOD exerts a delayed hypotensive action that is not enhanced by liposome encapsulation, suggesting it must diffuse to an extravascular site.

Decline in antioxidant capacity of Indian herbal teas during storage and its relation to phenolic content

The changes in the stability of antioxidant capacity with time and its relation to the phenolic content were evaluated in eight Indian herbal teas. These herbal teas are claimed to be antistress, immunomodulator, anti-aging, anti-inflammatory, appetizer, stimulant, blood purifier, energizer, antidepressant, antidiabetic, rejuvenative, analgesic, antiviral, nervine, diuretic, antihypertensive and memory enhancer. Antioxidant capacity was determined over a period of 15 months from the date of their procurement using assays for SOD mimetic activity, LPO inhibitory capacity and total thiol content, which decreased positively with time. Total phenolic content was determined spectrometrically according to the Folin-Ciocalteu method and calculated as gallic acid equivalents (GAE). Herbal teas with higher phenolic content showed a comparatively less decline in antioxidant capacity. The SOD mimetic activity values in control samples (at the time of procurement) were seen to be in the range of 54.63–93.64 units/min/mg of extract which after 15 months of storage decreased upto 7.4-folds in some samples. LPO inhibitory capacity was observed upto 96.75% in herbal tea E at the time of procurement which dropped to 63.85% inhibition of MDA formation/5μl of extract after 15 months. In case of total thiol, the values were seen in the range of 0.55–1.71 mg/g and after 15 months it was from 0.12 to 0.21 mg/g. In all these cases high antioxidant activity was seen in the samples with higher phenolic content which also showed comparatively less decline in antioxidant capacity after considerable storage time. The results have significance, as most of the herbal teas available in the local markets in India do not carry any information regarding the period of use without decline in its beneficial effects.

Crystal Structure and Superoxide Dismutase Activity of [Cu(ethylenediamine)2Cl][PF6

The preparation, spectroscopic properties, and crystal structure of chlorobis(ethylenediamine)copper(II) hexafluorophosphate [Cu(en)2Cl][PF6], (en=ethylendiamine) are reported. The complex crystallizes in the monoclinic system, space group P21/c, with cell constants a=6.1488(9) A, b=12.696(2) A, c=17.7424(17) A, β=97.265(12)°, and Z=4. The copper(II) ion is coordinated to two bidentate en molecules, to one chlorine ion, and to a more distant fluorine atom of the PF6 group, leaving the copper ion in a distorted octahedral coordination geometry. The superoxide dismutase mimetic activity of the complex was investigated using the indirect xanthine-xanthine oxidase- nitroblue tetrazolium method and compared to that of the native enzyme.

DNA strand scission by Fe(III) 2-methylaminopyridine complex and hydrogen peroxide.

Oxidative DNA damage is involved in mutagenesis, carcinogenesis, aging, radiation effects and also in the action of several anticancer drugs. Accumulated evidence indicates that iron may play an important role in these processes. The conversion of the closed circular double-stranded supercoiled plasmid pcDNA3 into the nicked circular and linear forms was used to investigate DNA nicking induced by the reactions of an iron complex of 2-methylaminopyridine (L), which exhibited a pronounced superoxide dismutase-mimetic activity and antitumour activity with H2O2. Hence the dose-response curve for the [FeL2Cl2]Cl.H2O-mediated H2O2-dependent DNA nicking was studied. For a fixed concentration of [FeL2Cl2]Cl.H2O (25 microM), the concentration of H2O2 producing a maximum extent of DNA nicking was 100 microM. The effects of these two constituents are synergistic. The biological antioxidants such as glycerol, sodium azide and superoxide dismutase significantly inhibited DNA breakage induced by [FeL2Cl2]Cl.H2O and hydrogen peroxide.

Amelioration of radiation-induced oxidative stress and biochemical alteration by SOD model compounds in pre-treated γ-irradiated rats

Introduction: The role of metalloelements in tissue maintenance, function and response to injury offer a new approach to decreasing and/or treating radiation injury. We investigated the roles of CuL 2SO 4, [MnL 2O] 2Cl 4(H 2O) 2 and [(VL 2O)(VL 2H 2O)]Cl 6 complexes (L=2-methylaminopyridine) of SOD-mimetic activities, in ameliorating the radiation-induced oxidative stress and alterations in some biochemical parameters in liver, kidney, spleen and brain in pretreated female rats exposed to γ-irradiation. Methods: Both untreated-rats and rats treated with the above complexes were subjected to whole-body γ-irradiation (6 Gy). 5′-Nucleotidase (5′-NT), acetylcholinesterase (AChE), adenosne triphosphatase (ATPase), superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GSSG-R) were assessed as well as liver DNA and RNA contents and total protein concentration were estimated in tissue homogenates of the above organs. The same parameters were assessed in non-irradiated treated rats and normal control rats. Results were compared to irradiated non-treated and normal control rats. Results: Pretreatment of γ-irradiated rats with Mn(IV) or V(IV) complex produced a significant decrease in liver 5′-NT activity compared to the corresponding value of the untreated irradiated rats. In contrast, liver DNA and RNA contents and brain AChE and ATPase activities were significantly increased in irradiated rat group pre-treated with these metal complexes. Cu II, Mn IV or V IV complex inoculation prior to irradiation of normal rats exhibited a significant increase in SOD, CAT, GSSG-R activities and protein content of liver, kidney, spleen and brain homogenates compared with that of the untreated irradiated rats. The treatment of non-irradiated rats with these complexes produced a highly significant increase in mean activities of SOD and CAT, with no changes in other parameters vs. controls. Conclusions: Cu(II), Mn(IV) and V(IV) 2-methylaminopyridine complexes offer a physiological approach to ameliorate the radiation-induced biochemical alterations. In addition, they provide sufficient protection against radiation injury of radiosensitive tissues.

Inhibition of Photohemolysis Induced by m-Chloroperbenzoic Acid by Metal Complexes with SOD-mimetic Activity

Red blood cells (RBCs) are probably the most common target through the damaging action of reactive oxygen species on the cells. The photohemolysis activity of m-chloroperbenzoic acid (CPBA) was concentration- and exposure time-dependent. Twenty minutes photo exposure time and 200 μm of CPBA concentration were optimum to study the effect of generated superoxide (O2-) and hydroxyl (•OH) radicals on RBCs. RBCs lysis photosensitized by CPBA was investigated in the presence of [(VL2O)(VL2H2O)]Cl6, [MnL2O]2Cl42H2O, [FeL2Cl2]Cl H2O, [CoL2Cl2]4H2O or [ZnL2Cl2]H2O respectively, where L is 2-methylaminopyridine, with SOD-mimetic activities with the aim of ascertaining their protective activity towards the photo induced cell damage. The decrease of photolytic activity caused by these complexes was concentration-dependent and the maximum percentage of protective activity was 75, 70, 68, 57 or 24% for [(VL2O)(VL2H2O)]Cl6, [MnL2O]2Cl4 2H2O, [FeL2Cl2]Cl H2O, [CoL2Cl2]4H2O or [ZnL2Cl2]H2O complex respectively, against the cell irradiated without addition of metal complexes. The comparison between the decrease of photolytic activity caused by these complexes and their SOD-mimetic activity of these metal complexes showed an appreciable correlation.

Identification of 100 KDa protein in sera of mice-treated with Cu(II) complex with superoxide dismutase-mimetic activity.

The protein profile of sera isolated from mice pre-treated with Cu(II) complex of Girard T with superoxide dismutase (SOD)-mimetic activity was analyzed using SDS-PAGE. This complex was intraperitoneally administered (10 mg/Kg body weight) to Swiss albino mice. The resolved polypeptides showed a new sharp band at 100 KDa against which a polyclonal antibody was raised in rabbit. Sera of rabbit anti-100 KDa protein was used as a powerful probe for the detection of 100 KDa protein isolated from sera of treated mice. Western blot assays revealed a strong reactive polypeptide band at 100 KDa in sera of the mice, but no cross reaction was observed with sera of normal mice. The identification of purified polypeptide was confirmed by different characterization experiments.

Prevention of biochemical changes in gamma-irradiated rats by some metal complexes.

The formation of superoxide partially accounts for the well-known oxygen enhancement of radiation-induced biochemical changes and cell damage. Radioprotective effects of copper (II), manganese (IV) or vanadium (IV) complexes, of superoxide dismutase-mimetic activity, on body weight, survival rate and some biochemical parameters in pre-treated irradiated, untreated irradiated and treated non-irradiated female albino rats have been studied 24 h after whole body gamma-irradiation at a dose level of 6 Gy. Survival time, body weight, red blood cell (RBC) and white blood cell (WBC) counts, hemoglobin (Hb) concentration, percentage of hematocrit (Hct%), reduced glutathione (GSH), serum total protein, albumin, globulin (G), blood urea, creatinine and cholesterol were estimated, as well as the activities of blood superoxide dismutase (SOD), glutamate-oxaloacetic (GOT) and glutamate-pyruvic (GPT) transaminases, and alkaline phosphatase were assessed. A significant decline was shown in body weight, survival rate, the mean values of RBC and WBC counts, Hb and Hct percentages, and GSH concentration, as well as blood SOD activity, in whole body gamma-irradiated rats compared with the control non-irradiated rat group. The mean activity values of alkaline phosphatase, GOT and GPT, as well as the average values of blood urea, creatinine, total cholesterol, total protein and globulin were significantly elevated, while the average values of albumin and the albumin/globulin ratio were decreased in gamma-irradiated rats compared with the corresponding values of the normal control rat group. Pretreatment of rats with either manganese or vanadium complexes resulted in a significant increase in survival rate and body weight over that of the non-treated irradiated rat group. Pretreatment of rats with copper (II), manganese (IV) or vanadium (IV) complexes caused a significant increase in RBC and WBC counts, Hb concentration, HCt (%), GSH content and SOD activity in blood when compared to the irradiated rat group without treatment. The administration of copper (II), manganese (IV) or vanadium (IV) complexes prior to irradiation exposure resulted in a significant decrease in GOT and GPT activities in addition to blood urea, creatinine, cholesterol, globulin and total protein contents, while each complex exhibited a significant increase in plasma alkaline phosphatase, albumin, and the albumin/globulin ratio compared to the untreated irradiated rat group. Administration of vanadium (IV), manganese (IV) or copper (II) complexes in non-irradiated rats caused a significant increase in SOD activity without changing other biochemical parameters compared with the corresponding values of the normal control rat group. We conclude that these metallo-elements, particularly manganese (IV) and vanadium (IV) complexes of 2-methylaminopyridine, have radiation protection and radiation recovery. Furthermore, these metal complexes offer a new approach to overcome the pathological effects of ionizing radiation and suggest their use as a physiological approach to preventing or perhaps predominantly facilitating recovery from radiation injury.

Crystal structure of the first SH-containing tetrahedral cobalt(II) complex, Co(quinoline)2(SH)2]. Superoxide dismutase activity

The preparation, spectroscopic properties and crystal structure of the bis-quinoline–bis-mercaptocobalt(II) complex [Co(quinoline)2(SH)2] are reported. The complex is tetrahedral with nitrogen donor atoms from two quinoline ligands and sulphur donor atoms from two mercapto groups. The superoxide dismutase mimetic activity of the complex was investigated using the indirect xanthine–xanthine oxidase–nitroblue tetrazolium method and compared to that of the native enzyme.

Development of novel copper(II) complexes of benzothiazole- N-sulfonamides as protective agents against superoxide anion. Crystal structures of [Cu( N-2-(4-methylbenzothiazole)benzenesulfonamidate)(2)(py)(2)] and [Cu( N-2-(6-nitrobenzothiazole)naphthalenesulfonamidate)(2)(py)(2)

Copper(II) ternary complexes based on the novel benzothiazole- N-sulfonamides, HL1 ( N-2-(4-methylbenzothiazole)benzenesulfonamide) and HL2 ( N-2-(6-nitrobenzothiazole)naphthalenesulfonamide) ligands, and pyridine have been synthesized and characterized. Complexes [Cu(L1)(2)(py)(2)] (1). and [Cu(L2)(2)(py)(2)] (2). were chemically characterized and their structures determined by means of single crystal X-ray analysis. In both compounds the Cu(II) ion is coordinated to four N atoms in a nearly square planar arrangement. The Cu-N bond distances are similar to those of Cu(2)Zn(2)SOD. The SOD mimetic activity of the complexes was determined both in vitro and in vivo. For determining the SOD-like activity of the complexes in vivo, we have developed a new method based on the complexes' protective effect on a delta sod1mutant of Saccharomyces cerevisiae against free radicals generated by hydrogen peroxide and menadione as well as free radicals produced in the cellular respiration process. The results have shown that complex 1 presents a protective action against oxidative stress induced by menadione or H(2)O(2) and that both complexes 1 and 2 protect against free radicals generated in cellular respiration.

Synthesis, crystal structure and superoxide dismutase mimetic activity of hexakis ( N-methylimidazole) copper(II) salicylate

The complex hexakis ( N-methylimidazole) copper(II) salicylate, [Cu( N-meim) 6](sal) 2, has been prepared from the reaction of copper(II) aspirinate with N-methylimidazole and was crystallographically and spectroscopically characterized. The complex crystallizes in the space group P2 1/c with a=13.324(2), b=7.870(1) and c=20.039(3) Å and β=108.41(1)°. It is structure that of a tetragonally distorted octahedral copper(II) cation with six coordinated N-methylimidazole ligands and two salicylate counter ions. The superoxide dismutase (SOD) mimetic activity of the complex has been investigated by utilizing xanthine–xanthine oxidase assay. The results indicate that the complex is potent SOD mimic.

Superoxide dismutase activity and electrochemical study of the binuclear [Cu(TSA) 2py] 2 complex

The superoxide dismutase-mimetic activity and the electrochemical behavior of the binuclear complex [Cu(TSA) 2py] 2 is reported. The complex exhibits a marked SOD activity in the nitroblue tetrazolium assay. Its redox response is in agrement with two copper atoms partially coupled through the carboxylate moieties. The electrode reactions lie in the range of the superoxide/peroxide and oxygen/superoxide couples. This fact is indicative that this complex can act as catalyst for the SOD reaction.

Crystal Structure and Superoxide Dismutase Activity of [Cu(Imidazole)2(Quinoline)Cl2]·0.5[Cu(Imidazole)4Cl2

The preparation, spectroscopic properties and crystal structure of (bis-imidazole)quinoline-copper(II) dichloride [Cu(Im)2(quin)Cl2] (Im = imidazole, quin = quinoline) and tetraimidazole-copper(II)-dichloride [Cu(Im)4Cl2] are reported. Both cocrystallize on the triclinic system, space group P-1, with cell constants a = 8.095(5) Å, b = 12.141(5) Å, c = 13.847(5) Å, α = 108.816(5)°, β = 104.173(5)°, γ = 94.965(5)° and Z = 2. In the [Cu(Im)2(quin)Cl2] complex the copper(II) ion is coordinated to two imidazole molecules, to one quinoline and two chlorine ions, with the copper(II) ion in a distorted trigonal bipyramidal coordination geometry. In the [Cu(Im)4Cl2] complex, the copper(II) ion has a distorted octahedral coordination geometry. The superoxide dismutase mimetic activity of the complexes was investigated using the indirect xanthine-xanthine oxidase-nitroblue tetrazolium method and compared to that of the native enzyme.

Protection by metal complexes with SOD-mimetic activity against oxidative gastric injury induced by indomethacin and ethanol in rats.

We have investigated the protective effect of oral administration of copper and manganese complexes with superoxide dismutase (SOD)-mimetic activity against oxidative gastric mucosal injury induced by the non-steroidal anti-inflammatory drug indometacin with ethanol in the rat. The total area of the gastric lesions and lipid peroxidation were significantly increased 1 h after oral administration of indometacin (15 mg/kg) and ethanol, indicating an acute oxidative injury. The activities of SOD, catalase (CAT), glutathione-S-transferase (GST) and glutathione content were significantly decreased in the gastric mucosa by indometacin plus ethanol. Manganese or copper complexes showed SOD-mimetic activity. Pretreatment with these complexes protected against gastric mucosal lesions and decreased lipid peroxides, as well as attenuating the decrease in the activities of SOD, CAT and GST in gastric mucosa. These findings suggest that active oxygen species and lipid peroxidation play an important role in the pathogenesis of gastric mucosal injury induced by indometacin. In addition, we have shown that Mn and Cu complexes have gastroprotective properties against ulceration induced by indometacin plus ethanol. The present results suggest that appropriate copper or manganese complex supplementation may potentially provide prophylaxis or therapy for some pathologies associated with excessive free radical production and inhibited SOD activity.