Effects Of Antioxidant Enzymes Research Articles

Effect of antioxidant enzymes and electrolytes of Aloe vera juice on the toxicity induced by ethionamide and para-aminosalicylic acid on Sprague-Dawley rats

Background: This aim is so widely used and believed to have healing properties that it is called “true aloe.” Aloe vera has been used for centuries to treat laxity and as a cleansing cleanser. Some of the most common health benefits of are as follows: Promotes wound healing, anti-fungal activity, hypoglycemia or antidiabetes effects, anti-inflammatory properties, anticancer properties, immobilomodulatory properties, and gastroprotective properties. Aims and Objectives: The objective of this study was to determine the antioxidant activity of A. vera juice against antituberculosis drugs ethionamide (ETH) and para-aminosalicylic acid (PAS) by quantifying antioxidant enzymes such as glutathione (GSH) and malondialdehyde (MDA) and catalase (CAT) and electrolytes in rats. Materials and Methods: Fresh leaves of A. vera were collected from botanical garden and the sample was identified. The sample was brought to the laboratory of the Department of Zoology at Patkar-Verde College, Goregaon, Mumbai. 50 g of leaves were ground with 50 mL of distilled water in a sterilized pestle and mortar and the yield so determined by comparing the weight of the extract with the weight of pulp. In the experiment, 48 Sprague-Dawley rats of either sex (average weight 150–250 g) were used. Each group was given the drugs ETH, PAS drug, and A. vera juice on a daily basis for 28 days. The serum of the rat was withdrawn and analyzed for antioxidant enzymes and electrolyte levels. Results: We observed a decrease in the level of GSH in rats treated with anti-tuberculosis (TB) drugs ETH and PAS. However, when A. vera juice was coadministered with PAS, either independently or in combination, it resulted in improved levels of GSH. In addition, the rats treated with A. vera juice showed a decrease in the level of MDA. Furthermore, coadministration of A. vera juice in combination with ETH + PAS + A. vera juice led to increased levels of CAT in rats. The concentration of Na+ in rats treated with A. vera juice in combination with ETH and PAS showed a decrease, which could potentially aid in normal metabolism. On the other hand, the elevation of K+ in the rats treated with A. vera juice indicates their adaptation to salinity, as K+ levels act somatically to prevent influx into roots and shoots. This elevation in K+ can be utilized to lower salt levels in rats experiencing stress. Moreover, the rats treated solely with A. vera juice exhibited the lowest level of Ca+, confirming their low salt stress condition. Finally, it was observed that the rats treated with A. vera juice experienced depletion in A. vera concentration. Conclusion: Based on the aforementioned findings, it can be inferred that A. vera is rich in phenolic and flavonoids, which exhibit antioxidant properties. This unequivocally demonstrates that possesses the ability to scavenge free radicals and plays a beneficial role in combating pathological conditions induced by reactive oxygen species. Furthermore, it has been established that reduces electrolyte levels and diminishes salt accumulation in comparison to groups administered with anti-TB medications ETH and PAS.

MODIFICATION OF NEURAL INTERACTIONS AND FUNCTIONAL ACTIVITY OF MEDIATOR SYSTEMS UNDER CONDITIONS OF METABOLIC SYNDROME

The review examines the peculiarities of mediator systems under the conditions of metabolic syndrome. The processes of oxidative stress that occur in adipose tissue are described and can be caused not only by an increase in ROS production, but also by a decrease in the antioxidant protection of adipocytes. Features of the eff ects of antioxidant enzymes are shown, which creates prerequisites for further study of their activity in various tissues against the background of metabolic disorders characteristic of metabolic syndrome. Convincing evidence is provided that functional changes in the expression, activity, and regulatory properties of neuronal NO synthase play a key role among the molecular causes of MS. Understanding the molecular basis of the functioning of the signifi cant components of the NO cycle, the patterns of their changes, the relationship between this cycle and oxidative and nitrosative stress will allow in the future to develop methods of more eff ective diagnosis, treatment and prevention of metabolic syndrome.

EFFECT OF Hoslundia opposita LEAFY VEGETABLE ON SOME ANTIOXIDANT ENZYMES IN SOME ORGANS OF NORMAL WISTAR RATS

Hoslundia opposita leaves were fed to wistar rats. Lipid peroxidation and the effects of antioxidant enzymes in the liver, heart and kidney were assessed. Thirty adult female rats (average weight of 110 ± 10gms) were used for the assay. The groups were five subgroups: consisting of control and four other groups fed with the rat chow mixed with varying concentrations of 200, 400, 600 and 800mg plant material/Kg body weight, respectively on a daily basis within a period of 12weeks. The level of peroxidation in the organs of the rat using Malondialdehyde (MDA) as a marker, showed fluctuations, in the MDA levels of the liver and kidney. However, the kidney showed significant increases at the end of the study while the liver and heart showed a decline. Catalase activities of the organs ( liver, kidney and heart ) decreased significantly (P<0.05) during the feeding of different concentration of the dried leaves respectively from (4.860 ± 0.330unit/min to 2.59 ± 0.40unit/min , 4.97 ± 0.230unit/min to 2.89 ± 0.56unit/min and 3.76 ± 0.840unit/min to 3.15 ± 0.35unit/min ). After six weeks of consuming400-800mg of the plant material/Kg body weight, a significant increase (P<0.05) in catalase was obtained in the kidney and heart which declined significantly thereafter. Superoxide diamutase (SOD) and glutathione peroxidise (GPx) generally increased in all groups in the liver, heart and kidney when compared with the control.The results revealed that the the plant could modulate antioxidant enzymes which could be due to the bioactive constituents of the leaves.

Effects of Loading-Weight in Both Hands on Antioxidant Enzyme Activity in Aerobic Training

The activities of serum super oxide dismutase(SOD) and catalase(CAT) are investigated among the aerobic exercise(AG), weight load aerobic exercise group(WG), and control group(CG) in aerobic training. Training done four times a week for 40minutes at a time is achieved during 12 weeks with 10 people in each group AG and WG. In WG, the each loading weight in both hands is 1kg. CG did not participate in aerobic training during 12 weeks. The results showed significant increases in activity for SOD and CAT in AG and WG. And the activity of SOD and CAT was higher in WG than AG. Therefore, it has been shown to have a positive effect on the effect of antioxidant enzymes when carried out with a heavy load on the hand during aerobic exercise. In conclusion, various training methods have been applied to improve aerobic abilities, but it is considered that training such as walking, running, and dancing by adding weight to the hands during these aerobic exercises will have a positive effect not only on antioxidant enzymes but also on obesity prevention and cardiovascular diseases. In addition, aerobic exercises performed by adding weight to the hands can be seen to increase energy consumption for activities by increasing the amount of work performed by the upper body. This increase in energy consumption is considered to be particularly significant for people with weak physical strength or for special patients.

Effects of Exogenous SA and H2O2 on Wheat-Seedling�s Antioxidant Enzymes in Different Temperatures

In order to clarify the compensation effect of exogenous salicylic acid (SA) and H2O2 on wheat growth, this paper, by setting different growth temperatures in the artificial climate chamber, has studied the effects of antioxidant enzymes and proline content of wheat seedlings with spraying SA, hydrogen peroxide (H2O2) and SA+H2O2. The results show that catalase (CAT) activity, in 0 and 5 �C is lower than 10 and 15 �C, while the peroxidase (POD) activity is opposite. The activity of ascorbate peroxidase (APX) increases gradually with temperature increasing. Exogenous SA, H2O2, and SA+H2O2 could effectively improve the activity of wheat antioxidant enzymes and the content of proline (Pro), while the SA+H2O2 treatment improves obviously.

EVALUATION OF ANTI EPILEPTIC ACTIVITY OF ETHANOLIC EXTRACT OF MURRAYA KAENIGII ON MES, PTZ INDUCED CONVULSIONS IN RATS

The aim of the study was to evaluate anti epileptic activity of ethanolic extract of M. kaenigii on MES, PTZ Induced convulsions in Rats. After the collection of the plant it was extracted with using ethanol solvent by maceration method. Preliminary Phytochemical analysis was done. Acute toxicity was studied. Assessments of antioxidant activity by assay of superoxide dismutase were done and also different enzyme analysis was studied. Effect of EEMK on ME induced convlusions was done in PHT treated animals. Secondary metabolites including alkaloids, saponins, cardiac glycosides and flavonoids were found to be present in the extract and these could have a wide range of compounds with pharmacological activities including those found in this study. Effect of antioxidant enzymes on MES and PTZ induced convolutions were studied. EEMK significantly inhibited the PTZ-induced convulsion, prolonged the latency for convulsion and decreased mortality. The PTZ kindling model is a widely used screening model for testing anticonvulsive compounds. Results based on the PTZ induced clonic seizures and MES induced generalized clonic-tonic seizures in rats model demonstrated that the ethanol extract of Murraya koenigii - Linn. is effective in reducing the severity of clonic seizures and generalized clonic-tonic seizures. This, therefore, supports the traditional use of the plant in the treatment of epilepsy.

Protoplast isolation for species in the Chamelaucium group and the effect of antioxidant enzymes (superoxide dismutase and catalase) on protoplast viability

An effective protocol for protoplast isolation from young leaves and somatic embryogenic cells of species in the Chamelaucium group and the use of superoxide dismutase (SOD) and catalase (CAT) to enhance protoplast viability are described. Mesophyll protoplasts were isolated from young leaves of a white Geraldton waxflower (Chamelaucium uncinatum) line 583, using a mixture of 1% (w/v) cellulase R10, 0.5% (w/v) macerozyme R10, and 0.1% (w/v) pectolyase. Viability of isolated mesophyll protoplasts increased dramatically when SOD and CAT were added. The highest increase of 7.61-fold in viability and 4.34-fold of viable protoplast yield were achieved when a combination of SOD at 500 units mL−1 and CAT at 2,000 units mL−1 was added to the enzyme mixture. Somatic embryogenic cell-derived protoplasts were isolated from embryogenic suspension cells of C. uncinatum line 583 when 1% (w/v) hemicellulase was added to a combination of 2% (w/v) cellulase R10, and 1% (w/v) macerozyme R10. Addition of SOD at 500 units mL−1 and CAT at 2,000 units mL−1 to the enzyme mixture improved viability only slightly, to above 90%, but improved yield significantly (6.6-fold). This combination of enzymes was also used to isolate protoplasts from embryogenic suspension cells of Chamelaucium repens and from young leaves of C. uncinatum, Actinodium calocephalum, Verticordia etheliana, Verticordia grandis, Verticordia hughanii, and Verticordia mitchelliana successfully with viability >80% and viable yield >7 × 105 cells g−1 fresh weight (or per milliliter packed cell volume in the case of suspension cells).

The effect of occupational stress on antioxidant enzymes

In this paper,the occupational stress influencing factors of nurses,the effect of the occupational stress on the occupation and especially the effect of antioxidant enzymes on the organism were summarized.Many research showed that the occupational overstress could have an impact on the the body physically and mentally.The effect of the occupational stress on the health was mainly analyzed and the relief strategies of occupational stress were studied,in order to effectively relieve occupational stress level of the target population,promote the physical and mental health. Key words: Occupational stress; Influencing factors; Health; Antioxidant enzymes; Relief strategy

Salicylic acid: physiological and biochemical changes in seeds and maize seedlings subjected to salt stress

Several plant species have development limitations on saline soils; however under water stress situations salicylic acid (SA) may have defense function by acting as antioxidant. Thereby, this study was aimed at analyzing physiological changes occurring in maize seeds treated with SA and germinated on sodium chloride moistened substrate; as well as assessing the effect of antioxidant enzymes produced by the seedlings. To this, seeds were soaked into zero and 1 mM SA solutions, for 60 min., and germinated on different NaCl concentrations (0, 30, 90, and 180 mM), and afterwards evaluated for germination, germination speed index, initial growth, and effect of antioxidant enzymes on seedlings. For electrical conductivity test, the seeds were previously soaked in NaCl solutions with and without SA. The SA application has minimized damages induced by salt stress to maize seed germination by favoring their germination percent; however without SA was not able on maintaining seed viability over 90 mM. Seedling initial growth was impaired by increasing NaCl concentrations in substrate; and electric conductivity has shown low values for release of solutes in the presence of SA. Activity of antioxidant enzymes has increased until 30 mM NaCl concentration; however above such concentration activity of these enzymes was reduced. The SA maintains germination of corn seeds above 90 mM NaCl; however, generally it is not efficient to ensure vigor of seedlings.

Effect of antioxidant enzymes, malondialdehyde, and respiratory variables of college judo athletes following maximal exercise

Effect of antioxidant enzymes, malondialdehyde, and respiratory variables of college judo athletes following maximal exercise

Effects of antioxidant enzymes in erythrocytes on pulmonary arterial pressure during hypoxic gas breathing

Using isolated rabbit lungs (n = 72) perfused at a constant flow of 70 ml/min, we analyzed whether the antioxidant system in erythrocytes significantly contributes to maintaining pulmonary vascular responsiveness to alveolar hypoxia (HPV) in normal lungs. As a measure of HPV, we observed the difference (delta P) between mean pulmonary arterial pressure during ventilation with normoxic gas mixture (21% O2, 5% CO2 in N2) and that during hypoxic gas breathing (3% O2, 5% CO2 in N2). Autologous erythrocytes obtained from the animals treated with various substances inhibiting either superoxide dismutase (SOD), the anion channel of the membrane, catalase (CAT) or glutathione peroxidase (GSH-Px). Subsequently, delta P was systematically measured in the perfusate, whose hematocrit was adjusted to 6-7% with normal or treated erythrocytes as described above. Further, the effects of adding SOD (75 U/ml) or CAT (1000 U/ml) to the perfusate on delta P were examined. The following results were obtained. (1) Inhibition of the superoxide scavenging mechanism in erythrocytes (SOD and anion channel) exerted no significant influence on delta P. (2) Inhibition of hydrogen peroxide scavengers in erythrocytes did not alter the scope of delta P. (3) Addition of either SOD or CAT to the perfusate did not show any significant effect on delta P. The findings are highly consistent with the idea that HPV in normal lungs is essentially independent of antioxidant enzymes in erythrocytes, which are expected to be one of the important factors determining the total capacity to deal with oxidant stress in the lung.

Mechanisms of induction of chromosomal aberrations by hydroquinone in V79 cells.

Hydroquinone occurs naturally in bacteria and plants and it is also manufactured for commercial use. Human exposure to this compound can occur by environmental, occupational, dietary and cigarette smoke exposure and from exposure to benzene, which can be metabolized to this compound. However, the main source of exposure to this compound is dietary, since hydroquinone is a naturally occurring compound in many foods. Hydroquinone can be metabolized to benzoquinones, which are potent haematotoxic, genotoxic and carcinogenic compounds that can also induce the formation of radical species, predisposing cells to oxidative damage. In order to clarify the involvement of radical species in the genotoxicity of hydroquinone, the induction of chromosomal aberrations in V79 cells was studied along with the assessment of the production of hydroxyl radicals at different pH values (6.0, 7.4 and 8.0), as well as the effect of antioxidant enzymes [catalase and superoxide dismutase (SOD)] on the clastogenic effect of hydroquinone. The results obtained indicate that the clastogenic activity of hydroquinone is dependent on the pH, suggesting that deprotonation is a fundamental step leading to DNA lesions under the experimental conditions used. The addition of S9 mix, SOD or SOD and catalase significantly decreased the clastogenic activity, suggesting the involvement of superoxide anion and hydrogen peroxide in the genotoxicity of hydroquinone. However, other species generated in the auto-oxidation process of hydroquinone, such as the semiquinone radical or the quinone, also seem to play a role in its genotoxicity, since the addition of antioxidant enzymes (catalase and SOD) or S9 mix do not lead to a complete abolition of the observed genotoxic activity. These results suggest the existence of at least two mechanisms associated with the genotoxic activity of this compound.

Saralasin, a Nonspecific Angiotensin II Receptor Antagonist, Attenuates Oxidative Stress and Tissue Injury in Cerulein-Induced Acute Pancreatitis

Free radical-mediated pancreatic injury is believed to play a key role in the pathogenesis of acute pancreatitis. Most of these studies have focused on the effects of antioxidant enzymes and free radical scavengers on improving the pancreatic injury. Recent findings showed that cerulein-induced acute pancreatitis was associated with an upregulation of a local pancreatic renin-angiotensin system in the pancreas. In the current study we hypothesized that inhibition of this renin-angiotensin system by saralasin, a nonspecific antagonist for angiotensin II receptor, could attenuate the severity of cerulein-induced pancreatitis. The effects of saralasin on oxidative stress and tissue injury in cerulein-induced pancreatitis were assessed by histopathologic analysis and on the basis of biochemical changes of plasma alpha-amylase level, pancreatic glutathione status, oxidative modification of protein, and lipid peroxidation. Data from the biochemical analysis showed that intravenous injections of saralasin at doses of 10 microg/kg to 50 microg/kg 30 minutes before the induction of acute pancreatitis significantly reduced pancreatic injury, as indicated by a decrease in plasma alpha-amylase activity in comparison with the cerulein-treated control. The effect of saralasin was further manifested by significant suppressions of glutathione depletion, oxidative modification of proteins, and lipid peroxidation in cerulein-treated rat pancreas. Histopathologic examination findings were in agreement with the biochemical data. These data suggest that prophylactic administration of saralasin can ameliorate the oxidative stress and tissue injury in cerulein-induced pancreatitis. Such a protective effect may provide new insight into the potential value of angiotensin II receptor antagonists in the clinical therapy for acute pancreatitis.

Effects of antioxidant enzymes in the molecular control of reactive oxygen species toxicology

Reactive Oxygen Species (ROS) are produced during normal cellular function. ROS include hydroxyl radicals, superoxide anion, hydrogen peroxide and nitric oxide. They are very transient species due to their high chemical reactivity that leads to lipid peroxidation and oxidation of DNA and proteins. Under normal conditions, antioxidant systems of the cell minimize the perturbations caused by ROS. When ROS generation is increased to an extent that overcomes the cellular antioxidants, the result is oxidative stress. It is now clear that several biological molecules, which are involved in cell signaling and gene regulation systems are very sensitive to redox statue of the cell. Antioxidants are substances that delay or prevent the oxidation of cellular oxidizable substrates. The various antioxidants exert their effect by scavenging superoxide, or by activating of a battery of detoxifying/defensive proteins. The prevention of oxidation is an essential process in all the aerobic organisms, as decreased antioxidant protection may lead to cytotoxicity, mutagenicity and/or carcinogenicity. This article also focuses on the mechanisms by which antioxidants and xenobiotics induce the gene expression of detoxifying enzymes. On the other hand, small molecules that mimic antioxidant enzymes are becoming new tools for the treatment of many diseases.

Increased activity of H 2O 2 in aorta isolated from chronically streptozotocin-diabetic rats: effects of antioxidant enzymes and enzyme inhibitors

The effects of hydrogen peroxide (H 2O 2, 1 nM–5 mM) on the tone of the rings of aorta precontracted with phenylephrine (PE) were studied in 4–5 months streptozotocin (STZ)-diabetic rats and their age-matched controls. H 2O 2 induced brief contraction before relaxation in endothelium-containing rings that was more pronounced in diabetic rats. Removal of the endothelium or pretreatment of rings with N G-nitro- l-arginine methyl ester ( l-NAME, 100 μM) abolished H 2O 2-induced immediate and transient increase in tone, but preincubation with indomethacin (10 μM) had no effect on contractions induced by H 2O 2 in both group of animals. Pretreatment with l-NAME or indomethacin as well as absence of endothelium produced an inhibition of H 2O 2-induced relaxation that was more pronounced in diabetic rings. Chronically STZ-diabetes resulted in a significant increase in H 2O 2-induced maximum relaxation that was largely endothelium-dependent. Decreased sensitivity (pD 2) of diabetic vessels to vasorelaxant action of H 2O 2 was normalized by superoxide dismutase (SOD, 80 U/ml). Pretreatment with SOD had no effect on H 2O 2-induced maximum relaxations in both group of animals but led to an increase in H 2O 2-induced contractions in control rats. When the rings pretreated with diethyldithiocarbamate (DETCA, 5 mM), H 2O 2 produced only contraction in control rats, and H 2O 2-induced relaxations were markedly depressed in diabetic rats. H 2O 2 did not affect the tone of intact or endothelium-denuded rings in the presence of catalase (2000 U/ml). Aminotriazole (AT, 10 mM) failed to affect H 2O 2-induced contractions or relaxations in all rings. Our observations suggest that increased production of oxygen-derived free radicals (OFRs) in diabetic state leads to a decrease in SOD activity resulting an increase in endogenous superoxide anions (O 2 •−), that is limited cytotoxic actions, and an increase in catalase activity resulting a decrease in both H 2O 2 concentrations and the production of harmful hydroxyl radical ( OH) in diabetic aorta in long-term. Present results indicate that increased vascular activity of H 2O 2 may be an important factor in the development of vascular disorders associated with chronically diabetes mellitus. Enhanced formation of OH, that is a product of exogenous H 2O 2 and excess O 2 •−, seems to be contribute to increased relaxations to exogenously added H 2O 2 in chronically diabetic vessels.

Induction of heme oxygenase in mammalian cells by mineral fibers: distinctive effect of reactive oxygen species.

Exponentially growing human-hamster hybrid [AL] cells treated with a 40 micrograms/ml (8 micrograms/cm2) dose of UICC standard reference chrysotile fibers induced heme oxygenase (HO) protein with a maximum expression level at 8 h post-treatment. While the constitutive HO expression was detectable in non-treated AL cells, the protein level was increased approximately 4.5-fold in fiber-treated cells. The induction was dose-dependent at fiber concentration between 2.5 micrograms/ml (0.5 microgram/cm2) and 40 micrograms/ml (8 micrograms/cm2) with the induced HO concentrated mostly in the cytoplasm as shown by immunostaining. Several other types of mineral fibers examined including crocidolites, tremolites, and erionites also induced HO synthesis with varying degree of efficiency. In general, chrysotile and crocidolite were more efficient inducers of HO than tremolite and erionite when compared at fiber doses that resulted in approximately 50% survival (LD50) level. The effects of antioxidant enzymes on HO induction were examined by concurrent treatment of fiber-exposed cultures with SOD and catalase. Although addition of superoxide dismutase (SOD) and catalase inhibited HO induction in a dose-dependent manner, they offered no protection on fiber-mediated clonogenic toxicity in the same population of treated cells. These results suggest that reactive oxygen species (ROS) produced by asbestos fibers play an essential role in the induction of HO and that different mineral fibers, when applied at equitoxic doses, often result in different oxidative stress status as determined by the induction of HO proteins.

Role of oxygen derivatives in the cytotoxicity and DNA damage produced by asbestos on rat pleural mesothelial cells in vitro.

The role of reactive oxygen metabolites in the toxic effects of asbestos on pleural mesothelial cells is not well defined. We exposed rat pleural mesothelial cells (RPMC) to chrysotile and crocidolite fibers (0-40 micrograms/cm2) in the presence or absence of catalase and superoxide dismutase (SOD). Cell injury was measured using the colorimetric 3-4 (5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and DNA damage was evaluated in terms of unscheduled DNA synthesis (UDS). Catalase (100 U/ml) and SOD (250 U/ml) protected RPMC against asbestos-induced cytotoxicity and DNA damage. However, the inactivated enzymes and bovine serum albumin also showed some protection, suggesting that the effect of antioxidant enzymes may be partly related to their protein nature. These results suggest that oxygen derivatives are partly involved in the toxic effects of asbestos on cultures of RPMC. The presence of extracellular proteins may also decrease asbestos-produced toxicity by reducing the degree of RPMC-fiber interaction.

Hydroxylated metabolites of the antimalarial drug primaquine. Oxidation and redox cycling.

Oxidation and redox cycling of the hydroxylated metabolites of the antimalarial drug primaquine (i.e. 5-hydroxyprimaquine, 5-hydroxydemethylprimaquine, and 5,6-dihydroxy-8-aminoquinoline) were studied. The three metabolites readily oxidized under physiological conditions, forming hydrogen peroxide and the corresponding quinone-imine derivatives as the main products. The latter compounds were characterized by visible, NMR, and infrared spectroscopy. Concomitant formation of drug-derived radicals and hydroxyl radicals was attested by direct and spin-trapping EPR experiments, respectively. The use of the spin stabilization method indicated that the radicals derived from 5-hydroxydemethylprimaquine and 5,6-dihydroxy-8-aminoquinoline are of the o-semiquinone type. Tentative structures are proposed for the radicals based on product identification and computer simulation of the experimental EPR spectra. The quinone-imines obtained from the reduced metabolites did not react at appreciable rates with NADPH but underwent redox cycling upon addition of ferredoxin:NADP+ oxidoreductase, forming hydrogen peroxide and hydroxyl radicals. The effect of antioxidant enzymes on hydroxyl radical yield obtained during oxidation and redox cycling indicates that the main route for hydroxyl radical formation is the metal ion-catalyzed reaction between the drug-derived radicals and hydrogen peroxide. Taken together, the results indicate that hydrogen peroxide is the potential toxic product formed from the primaquine metabolites.

Esr Detection of Free Radical Intermediates During Autoxidation Of 5-Hydroxyprimaquine

Autoxidation of 5-hydroxyprimaquine, a putative metabolite of the antimalarial primaquine, was studied by oxygen consumption and ESR spectroscopy. 5-Hydroxyprimaquine underwent fast autoxidation under mild conditions (pH 7.4-8.5, 25 degrees C, and presence of 1 mM diethylenetriamine pentaacetic acid); each mol of the drug consumed 0.75 mol of oxygen and formed 0.5 mol of hydrogen peroxide. Direct-ESR experiments demonstrated that 5-hydroxyprimaquine autoxidation was accompanied by generation of a drug-derived free radical that is oxygen sensitive. Generation of hydroxyl radical was also established by spin-trapping experiments in the presence of 5,5-dimethyl-1-pyrroline N-oxide. The effect of antioxidant enzymes on hydroxyl radical adduct yield and analysis of autoxidation stoichiometry suggest that the main route for hydroxyl radical generation is the iron-catalyzed reaction between the drug-derived free radical and hydrogen peroxide.