Efficacy of puffer fish (Takifugu rubripes) sauce in reducing hydroxyl radical damage to DNA assessed using the apurinic/apyrimidinic site method

Apurinic/apyrimidinic (AP) sites are frequently observed DNA lesions when cells are exposed to hydroxyl radicals. We developed a new method for measurement of the antioxidative activity of foods using the occurrence frequency of AP sites on DNA. Combined with the electron spin resonance (ESR) method as a standard method, we examined whether fish and soy sauces including puffer fish [Takifugu rubripes (Temminck et Schlegel)] sauce could protect DNA from damage caused by hydroxyl radicals. The results showed that the ratios of DNA protection by puffer fish sauce, salmon fish sauce, sandfish fish sauce (Shottsuru), colorless soy sauce, squid fish sauce (Ishiru), dark color soy sauce and light color soy sauce were 68.9, 67.0, 60.1, 49.7, 34.1, 28.2 and -4.4%, respectively. Puffer, salmon, and sandfish fish sauces showed high ratios of DNA protection against hydroxyl radicals. On the other hand, IC(50) values of hydroxyl radical scavenging of the puffer, salmon, sandfish, squid fish sauces and colorless, dark and light color soy sauces were 0.20, 0.09, 4.16, 0.26% and 0.28, 0.14 and 0.18%, respectively. Though the puffer fish sauce exhibited the highest level of DNA protection among the examined samples and a high hydroxyl radical scavenging capability, a correlation between the radical scavenging capability and DNA protection against hydroxyl radicals among the examined fish and soy sauces was not found.     

Relationship between peroxyl radical scavenging capability measured by the chemiluminescence method and an aminocarbonyl reaction product in soy sauce

Oxygen-related free radicals have been suggested as a cause of aging and various diseases, for example, various cancers and rheumatoid arthritis. Because of this a radical scavenger as an antioxidant has been sought in food materials. Soy sauce is a traditional fermented seasoning of East Asian countries and is available throughout the world. The relationship between the peroxyl radical scavenging capability using the luminol chemiluminescence method and melanoidin, the main product from aminocarbonylation, i.e., Maillard reaction, from soy sauce was examined. In this study, we report that soy sauce has a very high antioxidative capacity and from the comparisons of the IC50 values of 26 soy sauces in the case of the optical density of the soy sauce's color being standardized, it was found that not only melanoidin is an antioxidative product, but also other products have strong antioxidative properties.     

Effect of soy sauce on the antioxidative capacity of the gelatin gel food 'Nikogori' measured using the chemiluminescence method

Oxygen-related free radicals have been suggested as a cause of aging and various diseases, for example, various cancers and rheumatoid arthritis. Because of this a radical scavenger as an antioxidant has been sought in many foods. 'Nikogori' gelatin gel from cooked fish is a traditional food in Japan. Recently, 'Nikogori' has been noted as a readily consumed food for the elderly and those with medical problems associated with swallowing. In this study we report that the 'Nikogori' gelatin gels made from the collagen in various meats have a high peroxyl radical scavenging capability as the antioxidative capacity using the chemiluminescence method and the order of the strength of antioxidative capacity (IC(50) value) was the Japanese common squid mantle meat (0.163%) > flatfish (marbled sole) meat (0.534%) > chicken wing meat (0.585%) > beef shin meat (0.655%) > yellowtail meat (0.659%) > chub mackerel meat (0.789%). Furthermore, when soy sauce was added to the 'Nikogori' gelatin gel, the antioxidative capacity increased markedly to 0.098% of IC(50) value of yellowtail, 0.165% of chicken, 0.182% of flatfish and 0.252% of chub mackerel.     

Antioxidant properties of fruit and vegetable juices: more to the story than ascorbic acid

Dietary supplements such as vitamin C have become popular for their perceived ability to enhance the body's antioxidant defenses. Reactive oxygen species (ROS) have been shown to cause a broad spectrum of damage to biological systems. Scavenging of ROS is part of a healthy, well-balanced, antioxidant defense system. The present study used the Fenton reaction as a source of hydroxyl radicals and xanthine/xanthine oxidase as a source of superoxide radicals to investigate the scavenging capabilities of various fruit and vegetable juices against these radicals. Electron spin resonance (ESR) spin trapping was used for free radical detection and measurement. Using a colormetric assay, the present study also investigated the protective effects of fruit and vegetable juices against lipid peroxidation induced in cell membranes by hydroxyl radicals. The present study showed that the free radical scavenging capability of each individual juice, but not its ascorbic acid content, is correlated with its protective effect on free radical induced lipid peroxidation. The results indicate that ascorbic acid is only one facet of the protective effect of fruit and vegetable juices. It appears that consumption of whole fruits and vegetables would be superior to an ascorbic acid supplement for antioxidant effectiveness.     

Hepatocytes are protected by herb Phyllanthus niruri protein isolate against thioacetamide toxicity.

The herb, Phyllanthus niruri has been known to possess protective activity against various drugs and toxins induced hepatic disorders. Present study was conducted to evaluate the role of the protein isolate of the herb against thioacetamide (TAA)-induced cytotoxicity in mice hepatocytes. In vitro cell viability, lactate dehydrogenase (LDH) and alanine amino transferase (ALT) leakage were measured as the indicators of cell damage. In addition, measurement of the level of non-protein thiol, glutathione (GSH); activities of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST) as well as the extent of lipid peroxidation were carried out to evaluate the prooxidant-antioxidant status of the cell. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay was performed to determine the radical scavenging activity of the protein isolate. Results showed that the administration of the protein isolate prior to TAA exposure significantly reduced the release of LDH and ALT leakage and enhanced the cell viability in a dose-dependent manner in hepatocytes. Besides, the protein isolate appeared to prevent the alterations in GSH levels and activities of the anti-oxidant enzymes related to prooxidant-antioxidant status of hepatocytes. It also reduced the TAA-induced lipid peroxidation significantly as demonstrated by the reduction of malondialdehyde (MDA) production. DPPH radical scavenging assay showed that the protein isolate possessed radical scavenging activity. Combining, the data suggest that the protein isolate could protect hepatocytes from TAA-induced cellular injury probably by its antioxidative and radical scavenging properties.     

Ginkgo biloba leaf extract: review of biological actions and clinical applications

The number of studies on Ginkgo biloba leaves is rapidly increasing. A variety of effects of Ginkgo biloba leaf extract (GBLE) have been identified. GBLE contains many different flavone glycosides and terpenoides. GBLE has an antioxidant action as a free radical scavenger, a relaxing effect on vascular walls, an antagonistic action on platelet-activating factor, an improving effect on blood flow or microcirculation, and a stimulating effect on neurotransmitters. Besides a direct scavenging action on active oxygen species, GBLE exerts an anti-inflammatory effect on inflammatory cells by suppressing the production of active oxygen and nitrogen species. GBLE inhibited the increase in the products of the oxidative decomposition low-density lipoprotein (LDL), reduced the cell death in various types of neuropathy, and prevented the oxidative damage to mitochondria, suggesting that GBLE exhibits beneficial effects on neuron degenerative diseases by preventing chronic oxidative damage. The study using a model of ischemia-reperfusion injury has also demonstrated the protective effect of GBLE on cardiac muscle and its antioxidative action in vivo. Favorable results have been obtained in double-blind, placebo-controlled, comparative trials of patients with memory disorders, obstructive arteriosclerosis, and dementia. We review the recent studies on GBLE with respect to its various pharmacological actions, such as a scavenging activity on free radicals and an inhibitory action on lipid peroxidation. GBLE shows a very strong scavenging action on free radicals, and is thus considered to be useful for the treatment of diseases related to the production of free radicals, such as ischemic heart disease, cerebral infarction, chronic inflammation, and aging.     

In Vitro Antioxidant Activities of the Fractions of Coccinia Grandis L. Leaf Extract

The present study was aimed at investigating the antioxidant activities of the various fractions of the hydromethanolic extract of the leaves of Coccinia grandis L. Voigt. (Cucurbitaceae). The antioxidant activities of the fractions have been evaluated by using nine in vitro assays and were compared to standard antioxidants such as ascorbic acid, α-tocopherol, curcumin and butylated hydroxyl toluene (BHT). All the fractions showed effective H-donor activity, reducing power, free radical scavenging activity, metal chelating ability and inhibition of β-carotene bleaching. None of the fractions exerted an obvious pro-oxidant activity. The antioxidant property depends upon concentration and increased with increasing amount of the fractions. The free radical scavenging and antioxidant activities may be attributed to the presence of phenolic and flavonoid compounds present in the fractions. The results obtained in the present study indicate that the leaves of C. grandis are a potential source of natural antioxidant.     

Measurement of the radical scavenging activity of chicken jelly soup, a part of the medicated diet, 'Yakuzen', made from gelatin gel food 'Nikogori', using chemiluminescence and electron spin resonance methods

We reported that gelatin gel 'Nikogori' soup made from the collagen in chicken wing meat, which is a part of the medicated diet 'Yakuzen', has high peroxyl and hydroxyl radical scavenging activities as the antioxidative capacity using chemiluminescence and electron spin resonance methods. The peroxyl radical scavenging activity of the soy sauce and chicken jelly 'Nikogori' soup sample was much higher than that of the chicken-only sample (control) at 100 degrees C heating for 60 min, although the addition of soy sauce only slightly enhanced the hydroxyl radical scavenging activity. Although the addition of garlic slightly enhanced the hydroxyl radical scavenging activity, it strongly inhibited the peroxyl radical scavenging activity. We found that chicken jelly 'Nikogori' soup only and soup with the addition of soy sauce had the highest antioxidative capacity as part of the medicated diet, 'Yakuzen'.     

Chemical constituents and free radical scavenging activity of corn pollen collected from Apis mellifera hives compared to floral corn pollen at Nan, Thailand

ABSTRACT: BACKGROUND: Bee pollen is composed of floral pollen mixed with nectar and bee secretion that is collected by foraging honey (Apis sp.) and stingless bees. It is rich in nutrients, such as sugars, proteins, lipids, vitamins and flavonoids, and has been ascribed antiproliferative, anti-allergenic, anti-angiogenic and free radical scavenging activities. This research aimed at a preliminary investigation of the chemical constituents and free radical scavenging activity in A. mellifera bee pollen. METHODS: Bee pollen was directly collected from A. mellifera colonies in Nan province, Thailand, in June, 2010, whilst floral corn (Zea mays L.) pollen was collected from the nearby corn fields. The pollen was then sequentially extracted with methanol, dichloromethane (DCM) and hexane, and each crude extract was tested for free radical scavenging activity using the DPPH assay, evaluating the percentage scavenging activity and the effective concentration at 50% (EC50). The most active crude fraction from the bee pollen was then further enriched for bioactive components by silica gel 60 quick and adsorption or Sephadex LH-20 size exclusion chromatography. The purity of all fractions in each step was observed by thin layer chromatography and the bioactivity assessed by the DPPH assay. The chemical structures of the most active fractions were analyzed by nuclear magnetic resonance. RESULTS: The crude DCM extract of both the bee corn pollen and floral corn pollen provided the highest active free radical scavenging activity of the three solvent extracts, but it was significantly (over 28-fold) higher in the bee corn pollen (EC50 = 7.42 +/- 0.12 mug/ml), than the floral corn pollen (EC50 = 212 +/- 13.6% mug/ml). After fractionation to homogeneity, the phenolic hydroquinone and the flavone 7-O-R-apigenin were found as the minor and major bioactive compounds, respectively. Bee corn pollen contained a reasonably diverse array of nutritional components, including biotin (56.7 mug/100 g), invert sugar (19.9 g/100 g), vitamin A and beta carotene (1.53 mg/100 g). CONCLUSIONS: Bee pollen derived from corn (Z. mays), a non-toxic or edible plant, provided a better free radical scavenging activity than floral corn pollen.     

Antioxidative and <Emphasis Type="Italic">in vitro</Emphasis> antiproliferative activity of <Emphasis Type="Italic">Arctium lappa</Emphasis> root extracts

Background  

Arctium lappa, known as burdock, is widely used in popular medicine for hypertension, gout, hepatitis and other inflammatory disorders. Pharmacological studies indicated that burdock roots have hepatoprotective, anti-inflammatory, free radical scavenging and antiproliferative activities. The aim of this study was to evaluate total phenolic content, radical scavenging activity by DPPH and in vitro antiproliferative activity of different A. lappa root extracts.     

Clustered sensitivity to fungi: anaphylactic reactions caused by ingestive allergy to yeasts.

BACKGROUND: Respiratory allergy to environmental molds is relatively common, and fungal allergen-specific reactivity seems to cluster in certain persons. However, generalized reactions caused by ingested fungi have seldom been described. OBJECTIVE: To describe a mold-sensitized patient who developed multiple anaphylactic reactions after ingesting a yeast preparation widely used by the food industry as flavoring in, for example, powdered and ready-made sauces. METHODS: Skin prick tests and serum IgE tests were performed with inhalant and food allergens, including molds and yeasts, 2 pasta sauces consumed by the patient, individual sauce ingredients, and a food-quality yeast extract. Radioallergosorbent test inhibition was used for specificity studies. RESULTS: Skin prick and serum IgE test results were positive to several molds (Cladosporium herbarum, Alternaria alternata, Aspergillus fumigatus, and Penicillium notatum), baker's yeast (Saccharomyces cerevisiae), Malassezia furfur, and champignon and to the 2 pasta sauces, the yeast ingredient, and a food-quality yeast extract. Radioallergosorbent test inhibition studies confirmed that the sauces contain cross-reacting yeast and mold allergens. CONCLUSIONS: This patient has a clustered sensitization to fungi characterized by allergy to environmental fungal allergens and to yeast extracts used in the food industry. Yeasts should be considered as possible ingestive allergens in mold-allergic patients.     

Vasoactive Drugs Inhibit Oxygen Radical Production of Neutrophils

A concentration response study was performed to clarify whether vasoactive drugs, routinely used in intensive care patients, inhibit oxygen radical production of neutrophils. Moreover, in a cell-free system, it was investigated whether these drugs exert free radical scavenging properties. Vasoactive agents were incubated with neutrophils from healthy human volunteers, which were stimulated by N-formyl-methionyl-leucyl-phenylalanine (FMLP) and by opsonized zymosan to produce oxygen radicals, detected by chemiluminescence measurements. Sympathomimetics (epinephrine greater than norepinephrine, dopamine and dobutamine) as well as phosphodiesterase-inhibitors (amrinone and enoximone) inhibited FMLP-induced and zymosan-induced oxygen radical production of neutrophils in a concentration-dependent and drug-specific fashion. With the exception of amrinone, FMLP-induced chemiluminescence of neutrophils was impaired nearly 10-fold more markedly than zymosan-induced chemiluminescence. Glyceryl trinitrate, nifedipine and prostacyclin had no effect on oxygen radical production of neutrophils. In the cell-free system, epinephrine, norepinephrine, dopamine, amrinone and enoximone demonstrated oxygen free radical scavenging properties. This study shows that vasoactive drugs, frequently used in the clinical setting, may suppress oxidative burst after FMLP-receptor stimulation. As demonstrated in the cell-free system, this suppression was, at least in part, due to oxygen radical scavenging.     

Glutathione recycling is attenuated by acute ethanol feeding in rat liver.

The mechanism for ethanol-induced oxidative stress has been disputed because of the controversies on modulation of radical generating and scavenging activities by ethanol. In the present work, we attempted to clarify the acute effect of ethanol on the radical generating system as well as the radical scavenging system. For that purpose, chow-fed rats were given ethanol (5 g/kg) or isocaloric glucose solution by intragastric intubation and placed at 32 degrees C for 6 hr. Acute ethanol administration enhanced the expression of cytochrome P450 II E1(CYP II E1) in the liver and attenuated the activities of hepatic glutathione peroxidase (GPx) and reductase (GR). It also caused a significant increase in the level of hepatic thiobarbituric acid reactive substances (TBARS), an indicator of lipid peroxidation. On the other hand, acute ethanol feeding had no effect on the activities of catalase, xanthine oxidase (XO), glutathione transferase (GST) and glucose-6-phosphate dehydrogenase (G6PDH). From this result, it is suggested that acute ethanol administration causes the oxidative tissue damage by CYP II E1-associated radical generation and the decreased radical scavenging function due to the reduced activities of hepatic glutathione recycling system such as GPx and GR.     

Antioxidant, anticlastogenic and radioprotective effect of Coleus aromaticus on Chinese hamster fibroblast cells (V79) exposed to gamma radiation

Coleus aromaticus (Benth, Family: Laminaceae), Indian Oregano native to India and Mediterranean, is well known for its medicinal properties. A preliminary study was undertaken to elucidate in vitro free radical scavenging potential and inhibition of lipid peroxidation by C.aromaticus hydroalcoholic extract (CAE). Anti-clastogenic and radioprotective potential of CAE were studied using micronucleus assay after irradiating Chinese hamster fibroblast (V79) cells. CAE at 10, 20, 40, 60, 80, 100 and 120 mug/ml resulted in a dose-dependent increase in radical scavenging ability against various free radicals viz., 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), superoxide anion (O(2)(*-)), hydroxyl (OH(*)) and nitric oxide (NO(*)) generated in vitro. A maximum scavenging potential was noticed at 100 mug/ml and a saturation point was reached thereafter with the increasing doses of CAE. The free radical scavenging potential of the extract was in the order of DPPH > ABTS > Superoxide > Hydroxyl > Nitric oxide. CAE also exhibited a moderate inhibition of lipid peroxidation in vitro, with a maximum inhibition at 60 mug/ml (33%), attaining saturation at higher doses. The extract also rendered protection against radiation induced DNA damage, as evidenced by the significant (P < 0.05) decrease in the percentage of radiation-induced micronucleated cells (MN) and frequency of micronuclei (total). A maximum anticlastogneic effect/ radioprotection was noticed at a very low concentration i.e., 5 mug/ml of CAE, treated 1 h prior to 2 Gy of gamma radiation. A significant (P < 0.0001) anticlastogenic/radioprotective effect was also observed when the cells were treated with an optimum dose of CAE (5 mug/ml) 1 h prior to 0.5, 1, 2 and 4 Gy of gamma radiation compared with the respective radiation control groups. Overall, our results established an efficient antioxidant, anticlastogenic and radioprotective potential of CAE, which may be of great pharmacological importance.     

Free radical scavenging activity in the nonenzymatic fraction of human saliva: a simple DPPH assay showing the effect of physical exercise

Free-radicals and other reactive oxygen species (ROS) have been implicated as being major damaging species in pathology and they have been widely investigated. Using 1,1'-diphenyl-2-picrylhydrazyl (DPPH), we estimated total free radical scavenging activity in the low-molecular-weight nonenzymatic fraction (LMNEF) of human whole saliva. The activity of the whole saliva and serum were measured in terms of the rate of decrease in the absorbance at 517 nm in a 40% ethanol DPPH solution (pH 7.4) at room temperature. The DPPH activity of saliva and serum showed a significant linear relationship. The mean DPPH activities of saliva from 257 subjects aged 4-72 was found to be 0.389+/-.190 micromol/ml and bore no relation to age or sex. The activity in saliva of 86 subjects aged 4-11 was significantly different before and after exhaustive aerobic dance exercise for 1 hr. Physical exercise markedly decreased free radical scavenging activity in whole saliva of children. On the basis of the above results, we concluded that DPPH is useful for evaluating the total antioxidant capacity of LMNEF of human saliva.     

Protection of ionizing radiation-induced cytogenetic damage by hydroalcoholic extract of Cynodon dactylon in Chinese hamster lung fibroblast cells and human peripheral blood lymphocytes.

The radiomodulatory potential of hydroalcoholic extract of a medicinal plant Cynodon dactylon (family: Poaceae) against radiation-induced cytogenetic damage was analyzed using Chinese hamster lung fibroblast (V79) cells and human peripheral blood lymphocytes (HPBLs) growing in vitro. Induction of micronuclei was used as an index of cytogenetic damage, evaluated in cytokinesis blocked binucleate cells. The hydroalcoholic Cynodon dactylon extract (CDE) rendered protection against the radiation-induced DNA damage, as evidenced by the significant (p<0.001) reduction in micronucleated binucleate cells (MNBNC%) after various doses of CDE treatment in V79 cells and HPBLs. The optimum dose of CDE (40 and 50 microg/ml in HPBLs and V79 cells, respectively) with the greatest reduction in micronuclei was further used in combination with various doses of gamma radiation (0.5, 1, 2, 3, and 4 Gy) exposed 1 h after CDE treatment. A linear dose-dependent MNBNC% increase in radiation alone group was observed, while 40/50 microg/ml CDE significantly resulted in the reduction of MNBNC%, compared to the respective radiation alone groups. CDE resulted in a dose-dependent increase in free radical scavenging ability against various free radicals, viz., 2, 2-diphenyl-2-picryl-hydrazyl (DPPH); 2, 2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS); superoxide anion (O2*-); hydroxyl radical (OH*) and nitric oxide radical (NO*) generated in vitro. Also, an excellent (70%) inhibition of lipid peroxidation in vitro was observed at a dose of 300 microg/ml CDE, attaining the saturation point at higher doses. The present findings demonstrated the radioprotective effect of CDE, also rendering protection against radiation-induced genomic instability and DNA damage. The observed radioprotective effect may be partly attributed to the free radical scavenging and antilipid peroxidative potential of CDE.     

Synthesis and DPPH radical scavenging activity of 5-arylidene-N,N-dimethylbarbiturates

Twenty-four derivatives of N,N-dimethylbarbituric acid 1-24 were screened for their DPPH radical scavenging activity. These compounds showed an excellent antioxidant activity. A structure-activity relationship has been discussed, while all the synthetic compounds were characterized by spectroscopic techniques and elemental analysis.     

Composition, antifungal and radical scavenging activities of 4 propolis

HPLC/MS analysis revealed that the main constituents of Brazilian propolis A and B were artepillin C and drupanin, while those of New Zealand propolis C were pinocembrin, galangin and alkylphenol. No flavonoid or phenolic acid was detected in Japanese propolis D. Propolis C showed comparatively potent activity against growth of Trichophyton mentagrophytes, against filament formation of Candida albicans and potent scavenging activity against 1,1-diphenyl-2-picrylhyrazyl radical, but was less active against growth of C. albicans, as compared with those of thyme thymol essential oil, which was used as a positive control. Propolis A, B, and D were weak in antifungal activity, but showed more potent radical scavenging activity than thyme thymol oil. These results reveal the unique bioactivity of propolis, suggesting a possible application for antifungal therapy.     

Naringin,a citrus flavonone,protects against radiation-induced chromosome damage in mouse bone marrow

Free radicals are responsible for the induction of damage to the cellular DNA that leads to the formation of chromosome aberrations. Antioxidants are known to scavenge free radicals, thereby decreasing the degree of such effects. Radiation is a well-known inducer of free radicals and compounds that can scavenge free radicals may reduce radiation-induced DNA damage. Naringin, a bioflavonoid predominant in grapefruit and other citrus fruits, has been found to scavenge free radicals, therefore it may also reduce radiation-induced damage. The aim of the present study was to evaluate the radioprotective action of 2 mg/kg naringin in the bone marrow of mice exposed to different doses of (60)Co gamma-radiation by scoring the frequency of asymmetrical chromosomal aberrations. The irradiation of mice resulted in a dose-dependent elevation in the frequency of aberrant cells, acentric fragments, chromatid and chromosome breaks, dicentrics and exchanges. All these aberrations were elevated with scoring time up to 24 h post-irradiation and declined thereafter, except chromatid breaks, which were maximum at 12 h post-irradiation. Treatment of mice with 2 mg/kg body wt naringin before exposure to various doses of gamma-radiation resulted in a significant reduction in the frequencies of aberrant cells and chromosomal aberrations like acentric fragments, chromatid and chromosome breaks, centric rings, dicentrics and exchanges. The evaluation of free radical scavenging activity of naringin revealed a dose-dependent scavenging of hydroxyl, superoxide and 2,2 equal to or precedes -diphenyl-1-picryl hydrazyl radical. Naringin at 5 microM scavenged the 2,2-azino-bis-3-ethyl benzothiazoline-6-sulphonic acid cation radical very efficiently, where a 90% scavenging was observed. Our study demonstrates that naringin can protect mouse bone marrow cells against radiation-induced chromosomal damage.     

Neuroprotection against staurosporine by metalloporphyrins independent of antioxidant capability

Metalloporphyrin catalytic antioxidants are remarkably useful in protecting cells and tissues in a wide array of disease models, attributed primarily to functioning as superoxide dismutase (SOD) mimetics or by scavenging other reactive oxygen species (ROS). However, we recently showed that neuroprotection against Ca²⁺-dependent excitotoxic insults did not correlate with antioxidant strength or capability [25], raising the question of whether scavenging of ROS underlies neuroprotection in other types of neuronal injury. The protein kinase inhibitor staurosporine causes neuronal demise primarily by apoptosis. Neuroprotection from staurosporine by a limited number of metalloporphyrin antioxidants has previously been attributed to antioxidant action. In the current study, a wide array of anionic and cationic metalloporphyrins and porphyrins, ranging in antioxidant strength or capability, provided protection against staurosporine in cortical neuron and cerebellar granule neuron (CGN) culture. Neuroprotection did not correlate with antioxidant strength or capability. In CGN but not cortical neuron cultures, NMDA receptor antagonists also prevented neurotoxicity, so metalloporphyrins may also target this secondary mode of death induced by staurosporine. Neuroprotection observed with antioxidant-inactive controls raises the possibility of an additional, or perhaps alternative, mechanism by antioxidant analogs not involving ROS scavenging.