Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT00568 (ascorbate)
 23,072 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myrothamnus flabellifolia, a short woody shrub from southern Africa, can survive severe desiccation of its vegetative organs. We studied mechanisms protecting this plant from oxidative damage during desiccation for 2 weeks, 4 and 8 months, and also during subsequent rehydration. This plant retains high concentrations of chlorophyll during desiccation, and these chlorophyll molecules are probably a source for potentially harmful singlet oxygen production. Desiccation triggered substantial increases in zeaxanthin and redox shifts of the antioxidants glutathione and ascorbate towards their oxidised forms. Simultaneously, the concentrations of violaxanthin, beta-carotene, ascorbate, alpha-tocopherol, and glutathione reductase activity progressively decreased. Antheraxanthin, gamma-tocopherol, lutein, neoxanthin and glucose-6-phosphate dehydrogenase displayed less pronounced changes in response to desiccation. Even after 4 months of desiccation, Myrothamnus flabellifolia recovered rapidly upon rehydration. Re-watering induced formation of ascorbate and glutathione, simultaneous reduction of their oxidised forms, and rapid production of alpha-tocopherol and of various carotenoids. Only after 8 months of desiccation did the antioxidant system of M. flabellifolia break down; 3 weeks after the onset of rehydration, these plants abscised their leaves, but even then they were still able to recover and develop new ones. Ascorbate, beta-carotene and alpha-tocopherol were totally depleted after 8 months of desiccation and did not recover upon rehydration; glutathione was partly maintained, but only in the oxidised form. We present a model demonstrating which parts of antioxidant pathways break down as oxidative stress becomes detrimental and we discuss some potential implications of our results for the genetic modification of crop plants to improve their drought tolerance.
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PMID:Revival of a resurrection plant correlates with its antioxidant status. 1210 Apr 79

Fe excess is believed to generate oxidative stress. To contribute to the understanding of Fe metabolism, Fe excess was induced in Nicotiana plumbaginifolia grown in hydroponic culture upon root cutting. Toxicity symptoms leading to brown spots covering the leaf surface became visible after 6 h. Photosynthesis was greatly affected within 12 h; the photosynthetic rate was decreased by 40%. Inhibition of photosynthesis was accompanied by photoinhibition, increased reduction of photosystem II, and higher thylakoid energization. Fe excess seemed to stimulate photorespiration because catalase activity doubled. To cope with cellular damage, respiration rate increased and cytosolic glucose-6-phosphate dehydrogenase activity more than doubled. Simultaneously, the content of free hexoses was reduced. Indicative of generation of oxidative stress was doubling of ascorbate peroxidase activity within 12 h. Contents of the antioxidants ascorbate and glutathione were reduced by 30%, resulting in equivalent increases of dehydroascorbate and oxidized glutathione. Taken together, moderate changes in leaf Fe content have a dramatic effect on plant metabolism. This indicates that cellular Fe concentrations must be finely regulated to avoid cellular damage most probably because of oxidative stress induced by Fe.
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PMID:Effects of Iron Excess on Nicotiana plumbaginifolia Plants (Implications to Oxidative Stress). 1222 97

The effects of high alpha-linolenate content on lipid peroxidation, oxidative stress and loss of plant growth potential during ageing of potato (Solanum tuberosum L.) seed-tubers was examined. Endoplasmic reticulum (FAD3) and plastidal (FAD7) 18:2 fatty acid desaturases were upregulated in potato (cv. Desiree), resulting in a 2-fold average increase in mol percentage 18:3 in the total lipid fraction across all transgenic clones. In double-transformed (FAD3+7) tubers, high alpha-linolenate phenotype effected accelerated ageing, resulting in growth responses characteristic of older seed-tubers. Although respiration rates of wild-type (WT) and FAD3+7 tubers were equal at 7 months of storage, rates had increased by 23% and 50% in WT and FAD3+7 tubers, respectively, by 19 months of storage. Electrolyte leakage of tissue from 19-month-old FAD3+7 tubers was significantly greater than that from WT tubers of the same age, indicating that the high alpha-linolenate phenotype was detrimental to membrane integrity during long-term storage. On average, indices of lipid peroxidation (malondialdehyde, ethane, C-6 aldehydes) were higher in older FAD3+7 tubers, relative to WT tubers. Activities of glucose-6-phosphate dehydrogenase, peroxidase, glutathione reductase, ascorbate peroxidase and monodehydroascorbate reductase increased in tubers with advancing age and were higher, on average, in FAD3+7 tubers. Dehydroascorbate reductase activity decreased with age, with no difference between transgenic and WT lines. Collectively, these results indicate that FAD3+7 tubers underwent a higher degree of oxidative stress during ageing. The age-induced increase in respiration of FAD3+7 tubers was at least partly a response to fuel increased free radical scavenging through the ascorbate-glutathione antioxidant pathway. By affecting the susceptibility of lipids to peroxidation, the degree of fatty acid unsaturation influenced the development of oxidative stress and the overall rate at which growth potential was lost from seed-tubers during ageing. Thus, oxidative stress plays an integral role in modulating the ageing process to affect growth potential from potato seed-tubers.
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PMID:Oxidative metabolism and the physiological age of seed potatoes are affected by increased alpha-linolenate content. 1235 93

Free radicals and oxidative damage play important roles in aging and many degenerative disorders such as cancer, cardiovascular diseases, and Alzheimer disease. Antioxidants can alleviate some of the harmful effects of oxidative damage. In this report, we describe that we have been using human red blood cells (RBCs) as a model system to delineate the effects of oxidative damage on human cells, particularly on glucose-6-phosphate dehydrogenase (G6PD)-deficient human RBCs. By using a monolayer technique, we found that oxidative denaturation of hemoglobin leads to the release of hemin into the RBC membrane and the released hemin is capable of oxidizing membrane proteins via a thiyl radical intermediate as detected by the electron spin resonance technique. By using a Laser Viscodiffractometer (Vidometer) to measure RBC deformability, we found that the deformability of G6PD-deficient RBCs was drastically reduced by hydroxyl radicals. Perhaps as a consequence of enhanced susceptibility to oxidative stress, G6PD-deficient individuals have lower antioxidant levels, particularly vitamin C, than normal individuals. Interestingly, we have also found that RBC deformability could be affected by two environmental pollutants, namely, platinum and palladium, which can enhance hydroxyl radical formation in the presence of hydrogen peroxide and ferrous ion (Fenton reaction).
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PMID:Free Radical and Oxidative Damage in Human Blood Cells. 1238 88

Piper species, commonly used in diet and traditional medicine were assessed for their antioxidant potential. Catalase activity was predominated in Piper longum, followed by Piper cubeba, green pepper, Piper brachystachyum and Piper nigrum. P. nigrum was richest in glutathione peroxidase and glucose-6-phosphate dehydrogenase, green pepper was richest in peroxidase and vitamin C while vitamin E was more in P. longum and P. nigrum. P. brachystachyum and P. longum were rich sources of vitamin A. All the Piper species had GSH content of around 1 to 2 nM/g tissue. The antioxidant components of Piper species constitute a very efficient system in scavenging a wide variety of reactive oxygen species. Antioxidant potential of Piper species was further confirmed by their ability to curtail in vitro lipid peroxidation by around 30-50% with concomitant increase in GSH content.
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PMID:Enzymatic and non-enzymatic antioxidants in selected Piper species. 1525 5

The aim of the present study was to evaluate the protective effect of DL-alpha-lipoic acid on the biochemical changes, tissue peroxidative damage and abnormal antioxidant levels in the rat testis during cyclophosphamide (CP)-induced injury. Adult male Wistar rats were divided into four treatment groups: (I) control, (II) 15 mg/kg CP once a week for 10 weeks by gavage, (III) 35 mg/kg lipoic acid once a week for 10 weeks by intraperitoneal injection, and (IV) CP plus lipoic acid (24 h prior to CP administration). Testicular toxicity, assessed by decreased enzymatic activities of lactate dehydrogenase and glucose-6-phosphate dehydrogenase, was reversed with lipoic acid pretreatment. CP-exposed rats (group II) showed abnormal levels of enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and glutathione reductase) and antioxidants (reduced glutathione, ascorbate and alpha-tocopherol) along with high malondialdehyde levels. In contrast, rats pretreated with lipoic acid (group IV) showed normal lipid peroxidation and antioxidant defenses. These findings indicate a cytoprotective role of lipoic acid in this experimental model of testicular toxicity.
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PMID:Protective effect of DL-alpha-lipoic acid in cyclophosphamide induced oxidative injury in rat testis. 1550 81

Onions (Allium cepa L.) treated with external ascorbic acid or with the immediate precursor of its synthesis L-galactono-gamma-lactone show a stimulated elongation rate of the roots and an increase in the number of new radicles appearing at the bulb base. Treatment with both molecules resulted in an enhanced accumulation of ascorbate and dehydroascorbate along the root axis, but the distribution of these redox forms was not uniform along the root, as detected in intracellular (symplastic) and extracellular (apoplastic) compartments. Thus, those radicular zones metabolically more active, such as the meristem and the elongation zone, accumulated the highest amount of both redox forms of ascorbate. On the other hand, ascorbate and L-galactono-gamma-lactone also stimulated cytosolic glucose-6-phosphate dehydrogenase activity and inhibited peroxidase activity as deduced from in vivo and in vitro experiments. Differences were also found when comparing apoplastic and symplastic activities. These results are compatible with the idea of an ascorbate-mediated stimulation of root growth by inhibiting cell wall stiffening and increasing root metabolism.
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PMID:Changes in intracellular and apoplastic peroxidase activity, ascorbate redox status, and root elongation induced by enhanced ascorbate content in Allium cepa L. 1558 27

The present study investigates the prophylactic effect of Nymphaea alba against ferric nitrilotriacetate (Fe-NTA)-induced renal oxidative stress, hyperproliferative response and renal carcinogenesis in Wistar rats. Treatment with Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) enhanced iron-ascorbate-induced renal lipid peroxidation, xanthine oxidase, gamma-glutamyl transpeptidase and hydrogen peroxide (H2O2) generation with reduction in renal glutathione content, antioxidant enzymes, viz., glutathione peroxidase, glutathione reductase, catalase, glucose-6-phosphate dehydrogenase and phase-II metabolising enzymes such as glutathione-S-transferase and quinone reductase. It also elevated the levels of blood urea nitrogen, serum creatinine, ornithine decarboxylase (ODC) activity and thymidine [3H] incorporation into renal DNA. It also enhanced DEN-initiated renal carcinogenesis by increasing the percentage incidence of renal tumors. Treatment of rats orally with N. alba (100 and 200 mg/kg body weight) resulted in significant decrease in gamma-glutamyl transpeptidase, lipid peroxidation, xanthine oxidase, H2O2 generation, blood urea nitrogen, serum creatinine, renal ODC activity, DNA synthesis (p < 0.001) and incidence of tumors. Renal glutathione content (p < 0.01), glutathione metabolizing enzymes (p < 0.001) and antioxidant enzymes were also recovered to significant level (p < 0.001). Thus, our results show that N. alba is a potent chemopreventive agent and suppresses Fe-NTA-induced oxidative stress, hyperproliferative response and renal carcinogenesis in Wistar rats.
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PMID:Anticarcinogenic effect of Nymphaea alba against oxidative damage, hyperproliferative response and renal carcinogenesis in Wistar rats. 1588 50

Cyclophosphamide (CP), an alkylating agent widely used in cancer chemotherapy, causes fatal cardiotoxicity. In the present study, lupeol, a pentacyclic triterpene, isolated from Crataeva nurvala stem bark and its ester, lupeol linoleate were investigated for their possible cardioprotective effects against CP-induced toxicity. Male albino rats of Wistar strain were injected with a single dose of CP (200 mg/kg body weight, ip). In CP-administered rats, activities of lactate dehydrogenase and creatine phosphokinase were elevated in serum with a concomitant decline in their activities in the cardiac tissue. Significant increases (P<0.001) in the levels of lipid peroxides and a decrease (P<0.001) in the levels of enzymic (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and glutathione-s-transferase) and nonenzymic (reduced glutathione, vitamin C and vitamin E) antioxidants in the heart were also observed. The cardioprotective effects of lupeol (50 mg/kg body weight for 10 days orally) and its ester, lupeol linoleate (50 mg/kg body weight for 10 days orally) were evident from the significant reversal of the above alterations induced by CP. These observations highlight the antioxidant property of triterpenes and their cytoprotective action against CP-induced cardiotoxicity.
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PMID:Cardioprotective effect of pentacyclic triterpene, lupeol and its ester on cyclophosphamide-induced oxidative stress. 1600 98

The present study investigated the protective effect of DL-alpha-lipoic acid on the tissue peroxidative damage and abnormal antioxidant levels in cyclophosphamide (CP) induced hepatotoxicity. Male Wistar rats of 140 +/- 20 g were categorized into four groups. Two groups were administered CP (15 mg/kg body weight once a week for 10 weeks by oral gavage) to induce hepatotoxicity; one of these groups received lipoic acid treatment (35 mg/kg body weight intraperitoneally once a week for 10 weeks; 24 h prior to the CP administration). A vehicle (saline) treated control group and a lipoic acid drug control group were also included. The extent of liver damage in CP-induced rats was evident from the increased activities of serum aminotransferases, alkaline phosphatase and lactate dehydrogenase; whereas lipoic acid pretreatment prevented the rise in these marker enzymes. We evaluated the changes in activities/levels of tissue enzymic (superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase and glucose-6-phosphate dehydrogenase) and non-enzymic (reduced glutathione, ascorbate and a-tocopherol) antioxidants along with malondialdehyde levels in the experimental groups. In CP-administered rats the antioxidant enzymes showed significantly depressed activities (p < 0.001, p < 0.01) and the antioxidant molecules also showed depleted levels (p < 0.001, p < 0.01), in comparison with the control group. However the extent of lipid peroxidation and the abnormal antioxidant status were normalized in lipoic acid pretreated rats. The present work highlights the efficacy of lipoic acid as a cytoprotectant in CP-induced hepatic oxidative injury.
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PMID:Mitigation of oxidative stress in cyclophosphamide-challenged hepatic tissue by DL-alpha-lipoic acid. 1601 Sep 86


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