Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.3.5.1 (succinate dehydrogenase)
 8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to evaluate the interactive toxicity of ethanol with potassium dichromate (K2Cr2O7-chromium). Young, male Wistar rats (100-120 g) were divided into four groups of five or six animals each and were dosed, through water, with 10% ethanol (vol./vol.) or 25 ppm chromium or were dosed with a combination of ethanol+chromium at the same concentrations for a period of 22 weeks ad libitum and were maintained on normal diet. Control animals were maintained on a normal diet and water for the same period. The serum succinate dehydrogenase and liver total triglyceride levels were significantly reduced in the three treated groups. The serum alkaline phosphatase levels were significantly reduced in ethanol-treated rats, and there was no significant change in the acid phosphatase activity. Serum aspartate and alanine aminotransferase levels in the three treated groups were significantly increased. The liver glycogen significantly decreased in both the ethanol-treated and the chromium-treated rats. There was a significant increase in liver total cholesterol levels in chromium-treated rats. Total glutathione levels were significantly decreased in the livers of ethanol-treated and ethanol+chromium-treated rats. To further substantiate these findings, a histological examination of the liver and kidneys was undertaken. The livers of alcohol-treated animals showed altered hepatic architecture in the centrilobular and periportal areas, with increased sinusoidal space (space of Disse), vacuolation, and necrosis of hepatocytes. Similar changes were observed in a histological examination of the livers of chromium-treated rats, except that the damage to the hepatocytes was more confined to the periportal area. Moreover, histological examination of the livers of ethanol+chromium-treated rats revealed uniform damage in the centrilobular and periportal areas, as was observed in the groups treated either with ethanol or chromium. The histological examination of the kidneys in the three treated groups revealed significant damage to the renal tubules and Bowman's capsule, which showed vacuolation and degeneration of the basement membrane. These findings correlate well with the serum enzyme levels found in the treated groups. It is evident from this study that chronic ethanol consumption sensitizes the liver to the toxic action of agents such as chromium. It leads to impairment of the biochemical functions in the liver, and it causes liver and kidney damage. Long-term simultaneous exposure to ethanol and chromium may cause severe health problems in people who are alcoholics and work in chrome-plating and leather-tanning industries.
Alcohol 2001 Feb
PMID:A subtoxic interactive toxicity study of ethanol and chromium in male Wistar rats. 1133 Nov 7

Chronic alcohol consumption may potentiate acetaminophen (APAP) hepatotoxicity through enhanced formation of N-acetyl-p-benzoquinone imine (NAPQI) via induction of cytochrome P450 2E1 (CYP2E1). However, CYP2E1 induction appears to be insufficient to explain the claimed magnitude of the interaction. We assessed the role of selective depletion of liver mitochondrial glutathione (GSH) by chronic ethanol. Rats were fed the Lieber-DeCarli diet for 10 days or 6 weeks. APAP toxicity in liver slices (% glutathione-S-transferase alpha released to the medium, GST release) and NAPQI toxicity in isolated liver mitochondria (succinate dehydrogenase inactivation, SDH) from these rats were compared with pair-fed controls. Ethanol induced CYP2E1 in both the 10-day and 6-week groups by approximately 2-fold. APAP toxicity in liver slices was higher in the 6-week ethanol group than the 10-day ethanol group. Partial inhibition of NAPQI formation by CYP2E1 inhibitor diethyldithiocarbamate to that of pair-fed controls abolished APAP toxicity in the 10-day ethanol group only. Ethanol selectively depleted liver mitochondrial GSH only in the 6-week group (by 52%) without altering cytosolic GSH. Significantly greater GSH loss and APAP covalent binding were observed in liver slice mitochondria of the 6-week ethanol group. Isolated mitochondria of the 6-week ethanol group were approximately 50% more susceptible to NAPQI (25-165 micromol/L) induced SDH inactivation. This increased susceptibility was reproduced in pair-fed control mitochondria pretreated with diethylmaleate. In conclusion, 10-day ethanol feeding enhances APAP toxicity through CYP2E1 induction, whereas 6-week ethanol feeding potentiates APAP hepatotoxicity by inducing CYP2E1 and selectively depleting mitochondrial GSH.
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PMID:Selective mitochondrial glutathione depletion by ethanol enhances acetaminophen toxicity in rat liver. 1214 40

We investigated oxidative processes in mitochondria of Saccharomyces cerevisiae grown on ethanol in the course of chronological aging. We elaborated a model of chronological aging that avoids the influence of exhaustion of medium, as well as the accumulation of toxic metabolites during aging. A decrease in total respiration of cells and, even more, of the contribution of respiration coupled with ATP-synthesis was observed during aging. Aging is also related with the decrease of the contribution of malonate-insensitive respiration. Activities of citrate-synthase (CS), alpha-ketoglutarate dehydrogenase (KGDH) and malate dehydrogenase (MDH) were threefold decreased. The activity of NADP-dependent isocitrate dehydrogenase (NADP-ICDH) decreased more significantly, while the activity of NAD-dependent isocitrate dehydrogenase (NAD-ICDH) fell even greater, being completely inactivated on the third week of aging. In contrast, succinate dehydrogenase (SDH), enzymes of glyoxylate cycle (GCL) (isocitrate lyase (ICL) and malate synthase (MLS)), and enzymes of ethanol oxidation (alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ACDH)), were activated by 50% or more. The behavior of oxidative enzymes and metabolic pathways are apparently inherent to a more viable, long-lived cells in population, selected in the course of chronological aging. This selection allows cells to reveal the mechanism of their higher viability as caused by shunting of complete Krebs cycle by glyoxylate cycle, with a concomitant increased rate of the most efficient energy source, namely succinate formation and oxidation. Thiobarbituric-reactive species (TAR species) increased during aging. We supposed that to be the immediate cause of damage of a part of yeast population. These data show that a greater succinate contribution to respiration in more active cells is a general property of yeast and animal tissues.
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PMID:Inhibition of Krebs cycle and activation of glyoxylate cycle in the course of chronological aging of Saccharomyces cerevisiae. Compensatory role of succinate oxidation. 1498 99

We have isolated a Kluyveromyces lactis mutant unable to grow on all respiratory carbon sources with the exception of lactate. Functional complementation of this mutant led to the isolation of KlSDH1, the gene encoding the flavoprotein subunit of the succinate dehydrogenase (SDH) complex, which is essential for the aerobic utilization of carbon sources. Despite the high sequence conservation of the SDH genes in Saccharomyces cerevisiae and K. lactis, they do not have the same relevance in the metabolism of the two yeasts. In fact, unlike SDH1, KlSDH1 was highly expressed under both fermentative and nonfermentative conditions. In addition to this, but in contrast with S. cerevisiae, K. lactis strains lacking KlSDH1 were still able to grow in the presence of lactate. In these mutants, oxygen consumption was one-eighth that of the wild type in the presence of lactate and was normal with glucose and ethanol, indicating that the respiratory chain was fully functional. Northern analysis suggested that alternative pathway(s), which involves pyruvate decarboxylase and the glyoxylate cycle, could overcome the absence of SDH and allow (i) lactate utilization and (ii) the accumulation of succinate instead of ethanol during growth on glucose.
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PMID:The deletion of the succinate dehydrogenase gene KlSDH1 in Kluyveromyces lactis does not lead to respiratory deficiency. 1518 81

The neurotoxic effects of lead are controlled by a number of nutritional, physiological and environmental factors. One such factor, ethanol, might affect the neurotoxicity of lead by regulating its absorption and distribution. However, there is little information regarding the possible biochemical mechanism by which ethanol might be affecting the state of neuronal functions in lead-exposed individuals. Therefore, the present investigation involved the effect of alcohol (3 g/kg body weight, intragastrically, for 8 weeks) on lead-induced (50 mg/kg body weight, intragastrically, for 8 weeks) mitochondrial dysfunction in adult rat brain. Ethanol was found to enhance the toxic effects of lead in terms of decreased cellular energy reserves (ATP levels). Co-exposure to lead and ethanol caused marked decline in the rate of mitochondrial respiration as compared to lead alone. Further the activities of various components of the electron transport chain, viz. NADH dehydrogenase, succinate dehydrogenase and cytochrome oxidase depicted a significant decrease in the lead and ethanol co-exposed rats as compared to the lead-treated group. The results of the present study reflect that ethanol makes adult rat brain more vulnerable to the neurotoxic effects of lead in terms of altered mitochondrial energy metabolism.
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PMID:Impaired energy metabolism after co-exposure to lead and ethanol. 1591 Apr 12

Mitochondria play a central role in cellular energy metabolism. Oxidative phosphorylation occurs in the electron transport system of the inner mitochondrial membrane. Cytochrome aa3, b and c1 are encoded by mitochondrial DNA whereas cytochrome c is encoded by the nuclear gene, and these mitochondrial-DNA dependent cytochromes are decreased and electron transport at complex II, III and IV is disturbed in liver carcinomas and during carcinogenesis. The more the decreased cytochrome and oxidase activity are seen, the more significant is the increase in reactive oxygen species (ROS) production. ROS produced in mitochondria may be the main cause of nuclear-gene mutation in carcinogenesis. The mitochondrial dysfunction and overproduction of ROS plays a key role in progression of chronic hepatitis C and ethanol-induced liver injury. Ethanol also causes bacterial translocation in the intestine and the resulting lipopolysaccharides (LPS) activates Kupffer cells to produce pro-inflammatory cytokines. We suspect that non-alcoholic steatohepatitis (NASH) also is the result of increased ROS production in Kupffer cells and hepatocytes.
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PMID:Central role of mitochondria in metabolic regulation of liver pathophysiology. 1756 55

The development of fermentative yeasts secreting no organic acids is highly desirable for ethanol production coupled with membrane separation processes, because the acidic byproduct, succinic acid, significantly inhibits the membrane permeation of ethanol. Of the Pichia and Candida yeasts tested, Candida krusei IA-1 showed the highest ethanol productivity [55 g L(-1) day(-1) from 150 g L(-1) (w/v) of glucose], comparable to the strains of Saccharomyces cerevisiae, and produced much less of the acid (0.6 g L(-1) day(-1)) than the Saccharomyces strains (1.5-1.8 g L(-1) day(-1)) under semi-aerobic conditions. Interestingly, under aerobic conditions, strain IA-1 showed no production of the acid. Stain IA-1 exhibited a good assimilation of the acid, while S. cerevisiae NBRC 0216 showed no assimilation. The activity of succinate dehydrogenase (SDH) in strain IA-1 was 37.5 mU mg(-1), and 7.8-fold higher than that in S. cerevisiae strain NBRC 0216. More significantly, SDH1 was abundantly transcribed in strain IA-1, different from that in strain NBRC 0216, regardless of the culture conditions. From these results, C. krusei IA-1 efficiently takes up succinic acid and metabolizes it in the Krebs cycle, producing an extremely low level of byproducts in the culture medium. Therefore, C. krusei is not only a promising alternative to S. cerevisiae but also a suitable model for metabolic engineering of S. cerevisiae.
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PMID:Candida krusei produces ethanol without production of succinic acid; a potential advantage for ethanol recovery by pervaporation membrane separation. 1839 86

Dysfunction of the mitochondrial respiratory chain, being direct intracellular source of reactive oxygen species (ROS), is important in the pathogenesis of number of ageing associated human disorders. Effect of ethanol extract of Ganoderma lucidum on the activities of mitochondrial dehydrogenases; complex I and II of electron transport chain have been evaluated in the aged rat brain. Aged male Wistar rats were administered with ethanol extract of G. lucidum (50 and 250mg/kg, p.o) once daily for 15 days. Similarly DL-alpha-lipoic acid (100mg/kg, p.o) administered group was kept as the reference standard. Young and aged rats administered with water were kept as young and aged control, respectively. The effect of treatment was assessed by estimating the activities of succinate dehydrogenase (SDH), malate dehydrogenase (MDH), alpha-ketoglutarate dehydrogenase (alpha-KGDH), pyruvate dehydrogenase (PDH), complex I and II in the mitochondria of rat brain. Results of the study demonstrated that the extract of G. lucidum (50 and 250mg/kg) significantly (p<0.01) enhanced the activities of PDH, alpha-KGDH, SDH, complex I and II when compared to that of the aged control animals. The level of the lipid peroxidation was significantly lowered (p<0.01) in the G. lucidum treated group with respect to that of aged control. However, we could not find any statistically significant difference between the activities of enzymes in groups treated with 50 and 250mg/kg of G. lucidum. The activity exhibited by the extract of G. lucidum in the present study can be partially correlated to its antioxidant activity. The results of the study concluded that the extract of G. lucidum may effective to improve the function of mitochondria in aged rat brain, suggest its possible therapeutic application against ageing associated neurodegenerative diseases.
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PMID:Effect of Ganoderma lucidum on the activities of mitochondrial dehydrogenases and complex I and II of electron transport chain in the brain of aged rats. 1904 85

The protective effect of Emblica officinalis, a commonly used botanical in many Ayurvedic preparations, was investigated for its effects on liver mitochondria of ethanol-administered rats. Oxidative stress and reactive oxygen species-mediated toxicity are considered two of the key underlying mechanisms responsible for alcohol-induced liver injury and mitochondrial dysfunction. Alcohol-administered rats showed a significant elevation of plasma transaminases (aspartate and alanine aminotransferases), alkaline phosphatase, and gamma-glutamyl transferase compared to control rats. However, activities of hepatic mitochondrial antioxidant enzymes, viz., superoxide dismutase, glutathione peroxidase, and reduced glutathione, were significantly lower. Chronic alcohol feeding also increased lipid peroxide levels, protein carbonyl content, and overproduction of nitric oxide followed by lowered activities of NADH dehydrogenase, succinate dehydrogenase (SDH), and cytochrome c oxidase and content of cytochromes. Administration of E. officinalis fruit extract (EFE) at a dose of 250 mg/kg of body weight/day to alcoholic rats offers protection by simultaneously lowering the carbonyl content and lipid peroxidation and elevating antioxidant enzyme activities, SDH, NADH dehydrogenase, and cytochrome c oxidase activities, and content of cytochromes in hepatic mitochondria. Our data indicate that EFE administration to chronically alcohol-fed rats offers protection against alcohol-induced alterations. The active tannoid principles and nitric oxide scavenging compounds present in EFE may have contributed to the protection observed.
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PMID:Emblica officinalis protects against alcohol-induced liver mitochondrial dysfunction in rats. 1945 33

The function of mitochondrial Adh3 in the thermotolerant yeast Kluyveromyces marxianus was investigated. An ADH3-disrupted mutant exhibited growth retardation on non-fermentable carbon sources, except for ethanol, and this was suppressed by supplementation with antioxidants. Detailed analysis of the phenotype revealed that the mutant showed an increase in the activity of NADH dehydrogenase, sensitivity to H(2)O(2), and accumulation of reactive oxygen species (ROS), and that these carbon sources increased the activity of succinate dehydrogenase. The increase in both activities may reflect enhanced expression of both dehydrogenases by elevation of their substrate levels. The ROS level became low when antioxidants were added. These findings suggest that the ADH3 mutation and such carbon sources cause an elevation of the substrate level of the respiratory chain and eventually of the ROS level via increased expression of primary dehydrogenases, which in turn causes cell growth retardation. Adh3 might thus play a crucial role in the control of the NADH/NAD(+) balance in mitochondria.
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PMID:The crucial role of alcohol dehydrogenase Adh3 in Kluyveromyces marxianus mitochondrial metabolism. 1996 63


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