Attenuation of Oxidative Damage to Dna by Tairome and Taurine Analogs

Messina, S.; Dawson, Ralph

doi:10.1007/0-306-46838-7_40

Cited by 77 publications

(43 citation statements)

References 25 publications

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“…31,32 HTau also has been shown to protect against cell injury. 33, 34 We therefore assessed its capacity to protect against liver injury in the setting of oxidative stress. Despite a decreased PUFA/MUFA ratio, HTau did not prevent t-BHP liver injury, as obvious from increased serum ALT.…”

Section: Discussionmentioning

confidence: 99%

Metabolic insights into the hepatoprotective role of N-acetylcysteine in mouse liver

Zwingmann

Bilodeau

2006

Hepatology

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The hepatoprotective mechanisms of N-acetylcysteine (NAC) in non-acetaminophen-induced liver injury have not been studied in detail. We investigated the possibility that NAC could affect key pathways of hepatocellular metabolism with or without changes in glutathione (GSH) synthesis. Hepatocellular metabolites and high-energy phosphates were quantified from mouse liver extracts by 1 H-and 31 P-NMR (nuclear magnetic resonance) spectroscopy. 13 C-NMR-isotopomer analysis was used to measure [U-13 C]glucose metabolism through pyruvate dehydrogenase (PDH) and pyruvate carboxylase (PC). NAC (150-1,200 mg/kg) increased liver concentrations of GSH from 8.60 ؎ 0.48 to a maximum of 12.95 ؎ 1.03 mol/g ww, whereas hypotaurine (HTau) concentrations increased from 0.05 ؎ 0.02 to 9.95 ؎ 1.12 mol/g ww. The limited capacity of NAC to increase GSH synthesis was attributed to impaired glucose metabolism through PC. However, 300 mg/kg NAC significantly increased the fractional 13 C-enrichment in Glu (from 2.08% ؎ 0.26% to 4.00% ؎ 0.44%) synthesized through PDH, a key enzyme for mitochondrial energy metabolism. This effect could be uncoupled from GSH synthesis and was associated with the prevention of liver injury induced by tert-butylhydroperoxide and 3-nitropropionic acid. N -acetylcysteine (NAC) is the most widely administered antidote in acetaminophen intoxication. [1][2][3][4] In this setting, protection by NAC is believed to be attributable to its ability to regenerate glutathione (GSH) stores due to its capacity to provide cysteine (Cys) residues. However, NAC has also been shown to improve patient outcome after late administration, 5,6 pointing toward mechanisms independent from GSH replenishment. Furthermore, because NAC is recognized as an antioxidant, it might be useful in the setting of liver injuries different from those caused by acetaminophen intoxication. [6][7][8][9][10][11] NAC has also been reported to improve oxygen delivery, 4 to increase systemic oxygen consumption, 12 and to have beneficial effects on liver blood flow and function. 6,8,10 Because liver oxygen consumption is coupled with aerobic oxidation of energy substrates in the mitochondrial tricarboxylic acid (TCA) cycle, we hypothesize that NAC might improve hepatocellular energy metabolism. This effect might be salutary in the setting of nonacetaminophen-induced liver injury.We were particularly interested in investigating how NAC is involved in hepatocellular metabolic pathways and whether these changes are associated with modulation of GSH synthesis. The liver is unique in its metabolic activity and harbors many interrelated pathways. Apart

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Section: Discussionmentioning

confidence: 99%

Metabolic insights into the hepatoprotective role of N-acetylcysteine in mouse liver

Zwingmann

Bilodeau

2006

Hepatology

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“…2F), consistent with the likelihood that TRAP1 KO cells are constitutively exposed to elevated oxidative stress. Interestingly, taurine, hypotaurine, and propionylcarnitine have all been reported to protect cells from oxidative stress (23)(24)(25)(26)(27)(28)(29). Thus, the elevated levels of these metabolites in TRAP1 KO cells (Fig.…”

Section: Trap1 Deficiency Is Associated With Increased Mitochondrial mentioning

confidence: 96%

Molecular chaperone TRAP1 regulates a metabolic switch between mitochondrial respiration and aerobic glycolysis

Yoshida

Tsutsumi²,

Mühlebach

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

229

272

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TRAP1 (TNF receptor-associated protein), a member of the HSP90 chaperone family, is found predominantly in mitochondria. TRAP1 is broadly considered to be an anticancer molecular target. However, current inhibitors cannot distinguish between HSP90 and TRAP1, making their utility as probes of TRAP1-specific function questionable. Some cancers express less TRAP1 than do their normal tissue counterparts, suggesting that TRAP1 function in mitochondria of normal and transformed cells is more complex than previously appreciated. We have used TRAP1-null cells and transient TRAP1 silencing/overexpression to show that TRAP1 regulates a metabolic switch between oxidative phosphorylation and aerobic glycolysis in immortalized mouse fibroblasts and in human tumor cells. TRAP1-deficiency promotes an increase in mitochondrial respiration and fatty acid oxidation, and in cellular accumulation of tricarboxylic acid cycle intermediates, ATP and reactive oxygen species. At the same time, glucose metabolism is suppressed. TRAP1-deficient cells also display strikingly enhanced invasiveness. TRAP1 interaction with and regulation of mitochondrial c-Src provide a mechanistic basis for these phenotypes. Taken together with the observation that TRAP1 expression is inversely correlated with tumor grade in several cancers, these data suggest that, in some settings, this mitochondrial molecular chaperone may act as a tumor suppressor.M olecular chaperones help to maintain cellular homeostasis.The heat-shock protein 90 (HSP90) family of molecular chaperones is highly conserved from bacteria to mammals. HSP90 itself is an essential molecular chaperone found in the cytoplasm and nucleus of all eukaryotic cells (1, 2). In multicellular eukaryotes, the HSP90 family includes the mitochondrial chaperone TRAP1 (TNF receptor-associated protein), which shares 50% sequence similarity with HSP90. Although TRAP1 binds and hydrolyzes ATP in an analogous manner to HSP90 (3), its cellular function is less well understood. Thus, although many HSP90-dependent proteins ("clients") and interacting cochaperones have been described (www.picard.ch/downloads/Hsp90interactors.pdf), the validated list of TRAP1-dependent clients is quite small and TRAP1-interacting cochaperones, if they exist, have yet to be identified (4).Several studies have suggested that TRAP1 plays a cytoprotective role by buffering reactive oxygen species (ROS)-mediated oxidative stress (5, 6), and others have reported that TRAP1 overexpression attenuates ROS production (7). The antioxidant properties of TRAP1, together with its reported ability to regulate opening of the mitochondrial permeability transition pore (8, 9), may contribute to its antiapoptotic activity (4). For these reasons, TRAP1 has been proposed as an anticancer molecular target, and first-generation inhibitors have shown some anticancer activity in preclinical models (10). However, these inhibitors do not distinguish between HSP90 and TRAP1 (11), and TRAP1 expression in cancer is variable but HSP90 comprises as much as 5% of...

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“…Many studies revealed that, taurine (derivative of the amino acid cysteine, obtained from the bile of animals) can inhibit the cellular disorders by decreasing the oxidative stress and had a protective role against substances that induce liver fibrosis (Wingenfeld et al, 1996;You and Chang, 1998;Hardikar et al, 2001;Waer and Edress, 2006). Furthermore, Messina and Dawson (2000) mentioned that, MSG could be decreased the taurine level and consequently induce the accumulation of collagen fibers in the liver cells (Chen et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Ameliorative effects of melatonin on the liver of pregnant albino rats and their offspring induced by monosodium glutamate

2016

Res. Opin. Anim. Vet. Sci.

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Monosodium glutamate (MSG) is one of the most widely used food additives as a flavour enhancer but its high dose can induce toxic effects on the liver. Melatonin is a potent antioxidant, could ameliorate acute and chronic hepatic injury. The present work was essentially designed to evaluate the ameliorating role of melatonin on the liver of pregnant female Albino rats and their pups induced by MSG. In the present research, twenty four pregnant Albino rats were divided into four groups (n=6). The control group received saline solution, the melatonin group received 100 mg/kg b.wt, MSG treated group received 400 mg/kg b.wt and ameliorative group received MSG 400 mg/kg b.wt simultaneously with melatonin 100 mg/kg b.wt. All groups were received their corresponding dose from the 4 th day of gestation till the end of weaning period. The histological study of the current work revealed that MSG could induce damage of hepatocytes with cytoplasmic vacuolation, dilation of central vein and blood sinusoids, prominent Kupffer cells, infiltration cells around the portal area, variable degree of fibrosis, and scattered fatty cells. Furthermore, MSG consumption is also associated with ultrastructural alterations that varied considerably from mild structural changes to cytoplasmic lysis and degradation of some cellular organelles. Such alterations were represented by undifferentiated cytoplasm with dispersed vacuoles, nuclear pyknosis, swollen and vacuolated mitochondria, manifested dilated rough endoplasmic reticulum, remarkable aggregation of glycogen granules and fat droplets and obvious dispersion of collagenous fibers. Supplementation of melatonin ameliorated MSG-induced histopathological and ultrastrucural changes in liver cells. Keywords: MSG, Liver, Melatonin, Histopathlology, Fibrosis, TEM, HepatocytesTo cite this article: Abd El-Fattah BM El-Beltagy, 2016. Ameliorative effects of melatonin on the liver of pregnant albino rats and their offspring induced by monosodium glutamate. Res. Opin. Anim. Vet. Sci., 6(2): 59-68.

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Attenuation of Oxidative Damage to Dna by Tairome and Taurine Analogs

Cited by 77 publications

References 25 publications

Metabolic insights into the hepatoprotective role of N-acetylcysteine in mouse liver

Metabolic insights into the hepatoprotective role of N-acetylcysteine in mouse liver

Molecular chaperone TRAP1 regulates a metabolic switch between mitochondrial respiration and aerobic glycolysis

Ameliorative effects of melatonin on the liver of pregnant albino rats and their offspring induced by monosodium glutamate

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