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PubMed2000

Effect of pentacyclic triterpenes on oxalate-induced changes in rat erythrocytes.

Investigations were carried out to evaluate the effect of two, structurally related, triterpenes-betulin and lupeol-on the membrane peroxidation and antioxidant systems in red blood cells, during pyridoxine-deficient condition in rats. Increased lipid peroxidation levels in the absence and presence of ferrous sulphate, an inducer of lipid peroxidation, indicated peroxidative damage to the red-cell membrane. Na(+), K(+)-ATPase activity was decreased while that of other ion-specific ATPases were increased in the red cells of pyridoxine-deficient rats. Antioxidants, such as reduced glutathione, glutathione peroxidase, catalase, glutathione reductase and glutathione S-transferase were decreased, while superoxide dismutase alone was increased in the pyridoxine-deficient rat red blood cells. The red-cell osmotic fragility was found to be reduced. Treatment with the triterpenes proved effective in restoring the normal condition.

Animals↗

PubMed2001

Lupeol, a triterpene, inhibits early responses of tumor promotion induced by benzoyl peroxide in murine skin.

The modulating effect of Lupeol [lup-20(29)-en-3 beta -ol], a triterpene found in many fruits and medicinal plants, on benzoyl peroxide-induced tumor promotion responses or tumor promotion in murine skin is described. Benzoyl peroxide is an effective cutaneous tumor promoter acting through the generation of oxidative stress, the induction of ornithine decarboxylase activity and the enhancement of DNA synthesis. Benzoyl peroxide treatment increases cutaneous microsomal lipid peroxidation and hydrogen peroxide generation. The activity of the cutaneous antioxidant enzymes, namely catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase, is decreased and levels of cutaneous glutathione are depleted. Benzoyl peroxide treatment also induces ornithine decarboxylase activity and enhances [3H]thymidine uptake in DNA synthesis. Prophylactic treatment of mice with lupeol (0.75 and 1.5 mg per animal) 1 hour before benzoyl peroxide treatment resulted in a diminution of benzoyl peroxide-mediated damage. The susceptibility of cutaneous microsomal membrane to lipid peroxidation and hydrogen peroxide generation was significantly reduced (P< 0.01 and P< 0.01, respectively). In addition, depleted levels of glutathione and inhibited activity of antioxidant enzymes were recovered to a significant level (P< 0.01, P< 0.05 and P< 0.01, respectively). Similarly, the elevated ornithine decarboxylase activity and enhanced thymidine uptake in DNA synthesis were inhibited significantly (P< 0.05) in a dose-dependent manner. The protective effect of lupeol was dose dependent in all parameters. The results suggest that lupeol is an effective skin chemopreventive agent that may suppress benzoyl peroxide-induced cutaneous toxicity.

Animals↗

PubMed2002

Effect of diquat on the antioxidant system and cell growth in human neuroblastoma cells.

Oxidative stress elicits an adaptive antioxidant response, which varies with tissue type. Diquat, a potent redox cycler that generates reactive oxygen species, has been used to study oxidative stress; however, its effect on the antioxidant system has not been characterized in neuronal cells. Accordingly, we measured antioxidant parameters and cell growth in human neuroblastoma SH-SY5Y cells cultured for 48 h in medium containing 5, 10, or 25 microM diquat dibromide or phosphate-buffered saline. Viable cells were assayed for glutathione (GSH) and activities of catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPX), and glucose-6-phosphate dehydrogenase (GPDH). Mitochondrial function was evaluated by glutamate dehydrogenase (GDH) activity and MTT reduction. Diquat caused a marked concentration-related decrease in viable cell count ( by 26, 51, and 87% at 5, 10, and 25 microM diquat). Cell viability was only affected at 10 and 25 microM diquat and did not fully account for the decreased viable cell count. Concentration-related increases also occurred with GSH levels and a majority of antioxidant enzymes activities; however, the mode and magnitude varied with parameter. Increases in GSH, CAT, SOD, and GR were maximal at 25 microM diquat (to 3-, 6-, 2-, and 1.5-fold control values, respectively). GPDH activity was maximal at 10 microM diquat and then decreased to 86% of control activity at 25 microM diquat. GPX activity showed a concentration-related decrease (to 35% of control). Activity of the mitochondrial enzyme GDH increased 3-fold at 25 microM diquat, along with a lesser increase in MTT reduction. We conclude that diquat reduces cell growth in neuroblastoma cells and induces an adaptive antioxidant response, which are concentration dependent and occur at sublethal concentrations. At higher concentrations, diquat alters mitochondrial function and becomes increasingly toxic.

Antioxidants↗

PubMed1992

Variable alpha-tocopherol stimulation and protection of glutathione peroxidase activity in non-transformed and transformed fibroblasts.

Studies on glutathione metabolism in an established baby hamster kidney cell line (BHK-21/C13) and in its polyoma virus-transformed counterpart (BHK-21/PyY), have revealed a significant stimulation of intracellular glutathione peroxidase activity (Se-independent plus Se-dependent) by alpha-tocopherol supplementation (14 microM). This stimulation was found to be much greater in the transformed cells. Other GSH-requiring enzyme activities (namely glutathione reductase and glutathione transferase) were unaltered by alpha-tocopherol treatment, suggesting a degree of specificity in its action on GSHpx. In unsupplemented growth media, the GSHpx activity in both cell lines was significantly decreased by an oxidative stress. However, the same stress applied to the alpha-tocopherol-supplemented cells had no effect on the stimulated GSHpx activity, suggesting a protection afforded by the alpha-tocopherol.

Animals↗

PubMed1995

Expression of Arabidopsis cytosolic ascorbate peroxidase gene in response to ozone or sulfur dioxide.

The effects of ozone or sulfur dioxide on antioxidant enzymes were investigated in Arabidopsis thaliana. Plants were fumigated with 0.1-0.15 ppm ozone or sulfur dioxide up to about 1 week in an environment-controlled chamber. Both pollutants increased the activities of ascorbate peroxidase and guaiacol peroxidase in leaves, but had little effect on the activities of superoxide dismutase, catalase, monodehydroascorbate reductase, dehydroascorbate reductase or glutathione reductase. Ozone was more effective than sulfur dioxide in increasing the activities of the peroxidases. Ascorbate peroxidase activity increased 1.8-fold without a lag period during fumigation with 0.1 ppm ozone, while guaiacol peroxidase activity increased 4.4-fold with a 1-day lag. Expression of the APX1 gene encoding cytosolic ascorbate peroxidase was further investigated. Its protein levels in leaves exposed to 0.1 ppm ozone for 4 or 8 days were 1.5-fold higher than in controls. Both ozone and sulfur dioxide elevated APX1 mRNA levels in leaves at 4 and 7 days, whereas at 1 day only ozone was effective. The induction of APX1 mRNA levels by ozone (3.4- to 4.1-fold) was more prominent than that by sulfur dioxide (1.6- to 2.6-fold). The APX1 mRNA level increased by day and decreased by night. Exposure of plants to 0.1 ppm ozone enhanced the APX1 mRNA level within 3 h, which showed a diurnal rhythm similar to that of the control. These results demonstrate that near-ambient concentrations of ozone as well as similar concentrations of sulfur dioxide can induce APX1 gene expression in A. thaliana.

Air Pollutants↗

PubMed1996

Changes in antioxidative activities induced by Fe (II) and Fe (III) in cultured Vero cells.

The toxicity of iron (II) and iron (III) chlorides was studied at different biochemical and cellular levels, including antioxidative and metabolic enzymes and two general indicators of cytotoxicity in Vero monkey kidney cells after 24-h exposure. Iron (II) was fourfold more toxic than Fe (III) in cell proliferation, with EC50 of 5.5 and 22 mM, respectively. Metabolic markers were far more sensitive than cytotoxicity assays at these concentrations. At the highest concentrations of toxicant tested [10 mM Fe(II) and 50 mM Fe(III)], both species produced nearly total inhibition of the relative uptake of neutral red (RNRU) and phosphofructokinase activity (PFK), and stimulated intracellular specific lactate dehydrogenase activity (LDH). Succinate dehydrogenase (SDH) and hexosaminidase (HEX) activities were reduced in dose-dependent manner, as was the antioxidative enzyme glucose-6-phosphate dehydrogenase (G-6-PDH) with both forms of iron. Glutathione reductase (GOR) and glutathione-S-transferase (GST) activities were stimulated by Fe (II) but were inhibited by the higher Fe (III) concentrations. In conclusion, the experimental model may be useful for the study of different metabolic effects induced by the two oxidation states of iron.

Animals↗

PubMed1991

Local treatment of cutaneous and subcutaneous metastatic malignant melanoma with fotemustine.

Fotemustine is a highly reactive chloroethyl-nitrosourea anti-tumor drug that is currently undergoing phase III clinical trials in stage IV metastatic malignant melanoma. The drug is a potent alkylating agent and rapidly chloroethylates the active sites of the important thioproteins thioredoxin reductase (TR), glutathione reductase (GR) and ribonucleotide reductase (RR). These enzymes control ribonucleotide reduction and, consequently, DNA synthesis in the S phase of the cell cycle. Side effects are minor due to the rapid metabolism of the drug. [14C]Fotemustine exhibited a half-life of 90 min in the vascular system after the administration of 100 mg/m2. Fotemustine was shown to yield the volatile degradation product acetylene (a) in distilled water (4.1%/h), (b) in melanoma cell culture medium (MCDB) supplemented with 10% fetal calf serum (33%/h) and (c) in fotemustine-sensitive human melanoma cells in culture medium (70.5%/h). Due to its rapid metabolism and its low toxicity, high concentrations of fotemustine (55 x 10(-3) M) were injected directly into cutaneous and subcutaneous melanoma metastases (n = 36) of seven patients, resulting in minor necrosis followed by total remission of the metastases. Untreated metastases adjacent to the treated tumors were not affected by fotemustine, confirming that rapid local metabolism of this drug occurs only in the vicinity of injected tumors without producing any systemic effects.

Adult↗

PubMed1985

Changes in the cardiac glutathione status after ischemia and reperfusion.

In the isolated and perfused rabbit heart ischemia induced a rapid decline of contractility, associated with a reduction of the content of tissue GSH with no significant changes in GSSG. Reperfusion induced a small recovery of contractility, a substantial release of total glutathione and a further decrease in the content of tissue GSH with a significant increase of tissue GSSG. Glutathione reductase and glutathione peroxidase activities were not affected by ischemia and reperfusion. This study suggests a possible role for glutathione in the determination of functional damage induced by myocardial ischemia and reperfusion.

Animals↗

PubMed2006

The non-psychoactive cannabidiol triggers caspase activation and oxidative stress in human glioma cells.

Recently, we have shown that the non-psychoactive cannabinoid compound cannabidiol (CBD) induces apoptosis of glioma cells in vitro and tumor regression in vivo. The present study investigated a possible involvement of caspase activation and reactive oxygen species (ROS) induction in the apoptotic effect of CBD. CBD produced a gradual, time-dependent activation of caspase-3, which preceded the appearance of apoptotic death. In addiction, release of cytochrome c and caspase-9 and caspase-8 activation were detected. The exposure to CBD caused in glioma cells an early production of ROS, depletion of intracellular glutathione and increase activity of glutathione reductase and glutathione peroxidase enzymes. Under the same experimental condition, CBD did not impair primary glia. Thus, we found a different sensitivity to the anti-proliferative effect of CBD in human glioma cells and non-transformed cells that appears closely related to a selective ability of CBD in inducing ROS production and caspase activation in tumor cells.

Cannabidiol↗

PubMed2006

Early diabetes-induced biochemical changes in the retina: comparison of rat and mouse models.

AIMS/HYPOTHESIS: Recently, various transgenic and knock-out mouse models have become available for studying the pathogenesis of diabetic retinopathy. At the same time, diabetes-induced retinal changes in the wild-type mice remain poorly characterised. The present study compared retinal biochemical changes in rats and mice with similar (6-week) durations of streptozotocin-induced diabetes. MATERIALS AND METHODS: The experiments were performed on Wistar rats and C57Bl6/J mice. Retinal glucose, sorbitol, fructose, lactate, pyruvate, glutamate, alpha-ketoglutarate and ammonia were measured spectrofluorometrically by enzymatic methods. Vascular endothelial growth factor (VEGF) protein was assessed by ELISA, and poly(ADP-ribosyl)ation by immunohistochemistry and western blot analysis. Free mitochondrial and cytosolic NAD(+)/NADH ratios were calculated from the glutamate and lactate dehydrogenase systems. RESULTS: Retinal glucose concentrations were similarly increased in diabetic rats and mice, vs controls. Diabetic rats manifested approximately 26- and 5-fold accumulation of retinal sorbitol and fructose, respectively, whereas elevation of both metabolites in diabetic mice was quite modest. Correspondingly, diabetic rats had (1) increased retinal malondialdehyde plus 4-hydroxyalkenal concentrations, (2) reduced superoxide dismutase (SOD), glutathione peroxidase, glutathione reductase and glutathione transferase activities, (3) slightly increased poly(ADP-ribose) immunoreactivity and poly(ADP-ribosyl)ated protein abundance, and (4) VEGF protein overexpression. Diabetic mice lacked these changes. SOD activity was 21-fold higher in murine than in rat retinas (the difference increased to 54-fold under diabetic conditions), whereas other antioxidative enzyme activities were 3- to 10-fold lower. With the exception of catalase, the key antioxidant defence enzyme activities were increased, rather than reduced, in diabetic mice. Diabetic rats had decreased free mitochondrial and cytosolic NAD(+)/NADH ratios, consistent with retinal hypoxia, whereas both ratios remained in the normal range in diabetic mice. CONCLUSIONS/INTERPRETATION: Mice with short-term streptozotocin-induced diabetes lack many biochemical changes that are clearly manifest in the retina of streptozotocin-diabetic rats. This should be considered when selecting animal models for studying early retinal pathology associated with diabetes.

Animals↗

PubMed2002

Induction of oxidative stress in the rat testis after short-term exposure to the organochlorine pesticide methoxychlor.

Methoxychlor is one of the environmental contaminants that has been shown to induce reproductive abnormalities in male rats. The mechanism of action of methoxychlor on the male reproductive system remains unclear. In the present study we have sought to investigate whether short-term administration of methoxychlor induces oxidative stress in the testis of adult rats. Methoxychlor (50, 100, or 200 mg/kg body weight per day) was administered orally for 1, 4, or 7 days. The animals were killed using anesthetic ether on the day following the last dosing. The weights of epididymides, seminal vesicles, and ventral prostate decreased after 50, 100, or 200 mg/kg per day for 7 days but remained unchanged after 1 and 4 days of treatment. The production of superoxide anion and hydrogen peroxide increased in the animals that received methoxychlor for 4 and 7 days. The activities of the antioxidant enzymes superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase decreased, while the level of lipid peroxidation increased in the testis after 4 or 7 days of treatment. The results indicated that short-term exposure to methoxychlor induces oxidative stress in the testis by decreasing antioxidant enzymes and increasing lipid peroxidation, possibly by inducing reactive oxygen species. In conclusion, the adverse effect of methoxychlor on the male reproduction could be due to induction of oxidative stress in testis.

Administration, Oral↗

PubMed2003

2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) induces oxidative stress in the epididymis and epididymal sperm of adult rats.

2,3,7,8-Tetrachlorodibenzo- p-dioxin (TCDD) is one of the most potent environmental contaminants, which has been shown to induce oxidative stress in testis and epididymal sperm of rats. However, the nature and mechanism of action of TCDD on the epididymis is not clear. The aim of the present study was to investigate whether induction of oxidative stress in epididymal sperm was direct effect of TCDD on epididymis. In the present studies, TCDD (0.1, 1.0 and 10 micro g/kg body weight per day) was administered orally to rats for 4 days. Twenty-four hours after the last treatment the animals were killed using anesthetic ether. Both epididymides were dissected out and epididymal sperm were collected by cutting the epididymides into small pieces in Ham's F-12 medium at 35 degrees C. The epididymal sperm and caput, corpus and cauda epididymides were homogenized and used for biochemical studies. Epididymal sperm counts did not decrease in the rats treated with TCDD. Administration of TCDD increased the production of reactive oxygen species such as hydrogen peroxide while the activities of antioxidant enzymes superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase were found to be decreased in the epididymal sperm as well as in cauda epididymides. Lipid peroxidation also increased in the epididymal sperm and in the various regions of the epididymides after exposure to TCDD. The results indicated that TCDD induces oxidative stress in the epididymis and epididymal sperm by decreasing the antioxidant enzymes through induction of reactive oxygen species. Thus, the adverse effects of TCDD on the epididymal sperm were due to direct effect of TCDD on epididymis.

Administration, Oral↗

PubMed2005

Time-course variations of DNA damage and biomarkers of oxidative stress in tilapia (Oreochromis niloticus) exposed to effluents from a swine industry.

DNA damage (Comet assay), lipoperoxidation levels (TBARS), and several biomarkers of oxidative stress such as catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione S-transferase (GST), and contents of reduced (GSH) and total (TG) glutathione were measured in liver and blood (Comet assay) of tilapia (Oreochromis niloticus) exposed for 7, 15, 30 (subchronic exposure), 60, and 90 days (chronic exposure) to two treatment lagoons of a swine-processing plant, the first an anaerobic lagoon and the second a final treatment lagoon. After the 15th day, TBARS increased in fish exposed to both lagoons, decreased on the 30th day, and on the 90th day remained similar to controls. Fish exposed subchronically and chronically to both effluents showed consistently greater DNA damage. The CAT and GPx activities showed similar profiles and were induced only during the first week and during the first and second months. GST activity was induced throughout the experimental period. On the other hand, GR activities showed inverted profiles, with progressively decreased activities in the liver of fish exposed to the anaerobic lagoon, and progressively increased activities in fish exposed to the final lagoon. GSH showed higher contents in liver after 60 and 90 days of exposure to the final lagoon. GSSG contents were higher in fish exposed to the final lagoon throughout the experimental period. After 15 days, tilapia exposed to both lagoons showed enhanced total glutathione contents. The hepatic antioxidant system and biomarkers of oxidative stress such as DNA fragmentation and TBARS contents of tilapia exposed to both lagoons presented biphasic profiles. These changes in the antioxidant status also indicate that the industrial treatment is not adequate to avoid damaging environmental effects.

Animals↗

PubMed1999

Biomarkers of oxidative stress and genotoxicity in livers of field-collected brown bullhead, Ameiurus nebulosus.

The objective of this investigation was to determine whether differences in a suite of biomarker assays in brown bullhead liver tissues could be detected and related to the pollution histories of two Ohio locations, one a reach of the Black River that had historically been severely impacted by the effluents of a coking plant, the other at Old Woman Creek, a freshwater estuarine research preserve. There were no gross differences in pathologies detectable in fish from either site, and the major difference found in bullheads at the two sites was in the relative liver weight (RLW). Differential responses of glutathione reductase, glutathione-S-transferase, Se-dependent glutathione peroxidase, Se-independent glutathione peroxidase, and oxidized glutathione have been reported between fish from contaminated and uncontaminated sites in other studies, but no such differences were observed in the present study. Of the oxidative stress biomarkers included in this investigation, only the responses of superoxide dismutase, catalase, and total glutathione appeared to correlate with environmental exposure of brown bullhead to polycyclic aromatic hydrocarbons. Results with single-strand DNA and ethoxyresorufin-O-deethylase were the reverse of what has been reported in most other studies, and may reflect adaptation of the fish at the previously highly contaminated site. The fish at the Black River site appear to have responded to the xenobiotics present in their environment by increasing their overall liver size, thereby increasing the overall amount of enzymes rather than altering the specific activity of a select set of protective enzymes.http://link.springer-ny. com/link/service/journals/00244/bibs/37n2p236.html

Animals↗

PubMed2001

Oxidative damage of erythrocytes: a possible mechanism for premature hemolysis in experimental visceral leishmaniasis in hamsters.

Visceral leishmaniasis is accompanied by severe anemia and pancytopenia. Reactive oxygen species are known to contribute to the pathogenesis of several red blood cell (RBCs) disorders. The present study reveals the extent of oxidative stress and the efficacy of the primary antioxidant system in erythrocytes of hamsters in the progressive anemic response at different stages of leishmanial infection. Increased intracellular precipitation of Heinz bodies secondary to oxidative denaturation of hemoglobin and enhanced formation of malonyldialdehyde suggest oxidative damage of erythrocytes, both in the hemoglobin and cell membrane, respectively. Decreased activities of superoxide dismutase and catalase in the infected animals indicate the generation of O2*- and H2O2, which in turn may produce the highly reactive *OH species. Decreases in the reduced glutathione level along with the decreased activities of glutathione reductase and glutathione peroxidase point to a deficient antioxidant defense system during the post-infection period. Accentuated degradation of both cytoskeletal and integral membrane proteins after 3 months of infection may eventually lead to membrane destabilization and early lysis of erythrocytes in experimental visceral leishmaniasis.

Animals↗

PubMed2007

Oxidant/antioxidant status in men with Behçet's disease.

Behçet's disease (BD) is a chronic, progressive disorder that affects many systems of the body including the eye. The aim of this study was to assess whether the increase in oxidative stress in the affected tissues is reflected by lipid peroxidation and to check for alterations in antioxidants and antioxidant enzyme activities in patients with BD. Erythrocyte antioxidant potential (AOP), glutathione (GSH) and GSH-dependent enzymes (glutathione peroxidase (GSH-Px), glutathione reductase (GRD) and glutathione-S-transferase (GST), catalase (CAT), Cu-Zn superoxide dismutase (Cu-Zn SOD) activities, malondialdehyde (MDA) and some trace elements (zinc, Zn; copper, Cu; manganese, Mn) levels in men with BD. Erythrocyte CAT, GSH-Px activities, MDA, GSH, AOP and serum Zn values were significantly lower in patients with BD than in the control group. However, erythrocyte Cu-Zn SOD, GRD activities, erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) and Cu values were significantly higher in patients with BD than in the control group, but GST activity and serum Mn values were unchanged. In conclusion, our results confirm the presence of oxidative stress in patients with BD and suggest that the severity of BD may arise from impaired antioxidant mechanisms. Therapy with antioxidants may lead to the increase in the antioxidant defense system and thus improvement in clinical symptoms.

Adult↗

PubMed2006

Evaluating the effect of sulphated polysaccharides on cyclosporine a induced oxidative renal injury.

Cyclosporine A (CsA) has been universally used as an immunosuppressant for the management of organ transplantation and various autoimmune diseases. However, nephrotoxicity due to CsA remains to be an important clinical challenge. In the present investigation, an attempt has been made to appraise the effect of sulphated polysaccharides on oxidative renal injury caused by CsA. Adult male Wistar rats were divided into four groups. Two groups received CsA by oral gavage (25 mg/kg body weight) for 21 days to provoke nephrotoxicity, one of which simultaneously received sulphated polysaccharides subcutaneously, (5 mg/kg body weight). A vehicle (olive oil) treated control group and sulphated polysaccharides drug control were also built-in. An increase in lipid peroxidation along with abnormal levels of enzymic (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and glucose-6-phosphate dehydrogenase) and non-enzymic antioxidants (glutathione, vitamin C and vitamin E) are the salient features observed in CsA induced nephrotoxicity. CsA induced impairment of renal toxicity was evident from the marked decline in the activities of renal marker enzymes like alkaline phosphatase, acid phosphatase and lactate dehydrogenase, as well as an apparent increase in the serum urea, uric acid and creatinine; diagnostic of renal damage was normalized by sulphated polysaccharides co-administration. Sulphated polysaccharides treatment showed an effectual role in counteracting the free radical toxicity by bringing about a significant decrease in peroxidative levels and increase in antioxidant status. These observations emphasize the antioxidant property of sulphated polysaccharides and its cytoprotective action against CsA induced nephrotoxicity.

Animals↗

PubMed1992

Alterations in ATP-dependent calcium uptake by rat renal cortex microsomes following ochratoxin A administration in vivo or addition in vitro.

A disruption of calcium homeostasis, leading to a sustained increase in cytosolic calcium levels, has been associated with cytotoxicity in response to a variety of agents in different cell types. We have observed that administration of a single high dose or multiple lower doses of the carcinogenic nephrotoxin ochratoxin A (OTA) to rats resulted in an increase of the renal cortex endoplasmic reticulum ATP-dependent calcium pump activity. The increase was very rapid, being evident within 10 min of OTA administration and remained elevated for at least 6 hr thereafter. The increase in calcium pump activity was inconsistent with previous observations that OTA enhances lipid peroxidation (ethane exhalation) in vivo, a condition known to inhibit the calcium pump. However, no evidence of enhanced lipid peroxidation was observed in the renal cortex since levels of malondialdehyde and a variety of antioxidant enzymes including catalase, DT-diaphorase, superoxide dismutase, glutathione peroxidase, glutathione reductase and glutathione S-transferase were either unaltered or reduced. In in vitro studies, addition of OTA to cortex microsomes during calcium uptake inhibited the uptake process although the effect was reversible. Preincubation of microsomes with NADPH had a profound inhibitory effect on calcium uptake but inclusion of OTA was able to reverse the inhibition. Changes in the rates of microsomal calcium uptake correlated with changes in the steady-state levels of the phosphorylated Mg2+/Ca(2+)-ATPase intermediate, suggesting that in vivo/in vitro conditions were affecting the rate of enzyme phosphorylation.

Adenosine Triphosphate↗