31P and1H NMR spectroscopic studies of liver extracts of carbon tetrachloride-treated rats

Harvey, Peta J.; Gready, Jill E.; Hickey, Haruyo; Couteur, David G. Le; McLean, Allan J.

doi:10.1002/(sici)1099-1492(199910)12:6<395::aid-nbm568>3.0.co;2-m

Cited by 31 publications

(27 citation statements)

References 30 publications

(47 reference statements)

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“…The mechanisms responsible for the decline in hepatic ATP levels include: gradual loss of viable hepatocytes, which is likely to be an important contributing factoras the total amount of these cells per unit volume of liver decreases, MRS detectable signal from that volume will also decrease [6] ; anoxemia of local liver tissue induced by injury of capillary vessels after hepatic radiation [17] ; increased energy expenditure as liver disease progresses [18] . In addition, disturbed hepatic bioenergetics has also been ascribed to the capillarization of hepatic sinusoids during the development of cirrhosis [19] .…”

Section: The Changes In Hepatic Atp Levelssupporting

confidence: 49%

Biochemical metabolic changes assessed by³¹P magnetic resonance spectroscopy after radiation-induced hepatic injury in rabbits

Yu¹,

Hao²,

Dong³

et al. 2009

WJG

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AIM:To c o m p a re t h e fe a t u re s o f b i o c h e m i c a l metabolic changes detected by hepatic phosphorus-31 magnetic resonance spectroscopy ( 31 P MRS) with the liver damage score (LDS) and pathologic changes in rabbits and to investigate the diagnostic value of 31 P MRS in acute hepatic radiation injury. METHODS:A total of 30 rabbits received different radiation doses (ranging 5-20 Gy) to establish acute hepatic injury models. Blood biochemical tests, 31 P MRS and pathological examinations were carried out 24 h after irradiation. The degree of injury was evaluated according to LDS and pathology. Ten healthy rabbits served as controls. The MR examination was performed on a 1.5 T imager using a 1 H/ 31 P surface coil by the 2D chemical shift imaging technique. The relative quantities of phosphomonoesters (PME), phosphodiesters (PDE), inorganic phosphate (Pi) and adenosine triphosphate (ATP) were measured. The data were statistically analyzed. RESULTS:(1) Relative quantification of phosphorus metabolites: (a) ATP: there were significant differences among control group, mild injured group, moderate injured group, and severe injured group according to both LDS grading and pathological grading, respectively, and it decreased progressively with the increased degree of injury (r = -0.723, P = 0.000). (b) PME and Pi; the relative quantification of PME and Pi decreased significantly in the severe injured group, and the difference between the control group and severe injured group was significant (P < 0.05) (PME: LDScontrol group vs LDS-severe group, 0.86 ± 0.23 vs 0.58 ± 0.22, P = 0.031; pathological control group vs pathological severe group, 0.86 ± 0.23 vs 0.60 ± 0.21, P = 0.037; Pi: LDS-control group vs LDS-severe group, 0.74 ± 0.18 vs 0.43 ± 0.14, P = 0.013; pathological control group vs pathological severe group, 0.74 ± 0.18 vs 0.43 ± 0.14, P = 0.005) according to LDS grading and pathological grading, respectively. (c) PDE; there were no significant differences among groups according to LDS grading, and no significant differences between the control group and experimental groups according to pathological grading.(2) The ratio of relative quantification of phosphorus metabolites: significant differences (P < 0.05) (LDSmoderate group and LDS-severe group vs LDS-control group and LDS-mild group, 1.94 ± 0.50 and 1.96 ± 0.72 vs 1.43 ± 0.31 and 1.40 ± 0.38) were only found in PDE/ATP between the moderate injured group, the severe injured group and the control group, the mild injured group. No significant difference was found in other ratios of relative quantification of phosphorus metabolites. www.wjgnet.com CONCLUSION:3 1 P M R S i s a u s e fu l m e t h o d t o evaluate early acute hepatic radiation injury. The relative quantification of hepatic ATP levels, which can reflect the pathological severity of acute hepatic radiation injury, is correlated with LDS.

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Section: The Changes In Hepatic Atp Levelssupporting

confidence: 49%

Biochemical metabolic changes assessed by³¹P magnetic resonance spectroscopy after radiation-induced hepatic injury in rabbits

Yu¹,

Hao²,

Dong³

et al. 2009

WJG

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“…5 However, it has been reported that the ATP/ADP ratio does not change with age in isolated mitochondria of rat hepatocytes, 13 and similar patterns of change have been observed in rat livers rendered hypoxic experimentally 34 and in cirrhotic rat livers. 16 Therefore, our results are consistent with, but do not prove, the presence of intracellular hypoxia in aged livers secondary to impaired diffusion.…”

Section: Discussionmentioning

confidence: 99%

“…This technique has been described previously. 16,17 Spectroscopy was performed on the livers of 10 young, 10 middle-aged, and 8 old rats. Briefly, at laparotomy under anesthesia, the liver was sampled by freeze-clamping in situ using aluminum tongs precooled in liquid nitrogen.…”

Section: Ratsmentioning

confidence: 99%

Pseudocapillarization and associated energy limitation in the aged rat liver

2001

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Age-related impairment of drug metabolism by the liver is consistent with hepatocyte hypoxia, suggestive of the development of a diffusional barrier to oxygen supply. Because the effects of aging on the diffusional pathway (sinusoidal endothelium and space of Disse) have not been described, we performed comparative studies on the livers of Fischer F344 rats aged 4 to 7, 12 to 15, and 24 to 27 months. Lightmicroscopic examination revealed no evidence of fibrosis, cirrhosis, or other specific pathology. In contrast, scanning and transmission electron-microscopic examination revealed that aging is associated with pseudocapillarization of the sinusoidal endothelium, indicated by defenestration with reduced porosity, thickening of the endothelium, infrequent development of basal lamina, and only minor collagen deposits in the space of Disse. Furthermore, immunohistochemistry studies showed strong expression of collagen IV, moderate expression of factor VIII-related antigen, and weak expression of collagen I along the sinusoids of livers from old rats (P < .0001). In vitro 31 P magnetic resonance spectroscopy analysis showed that aging is associated with changes in high-energy phosphate and other metabolites, consistent with hepatocyte hypoxia. Aging in the liver is associated with changes in the sinusoidal endothelium and space of Disse that may restrict the availability of oxygen and other substrates. (HEPATOLOGY 2001;33:537-543.)The effect of aging in the liver is often considered to be of a lesser degree than in other organs. [1][2][3][4] The major recognized changes in the aging liver include reduction in liver mass and hepatic blood flow 1,4,5 ; however, it has been concluded that there are few other significant structural or biochemical changes in the liver. 1,2 On the other hand, even subtle agerelated changes may have profound consequences for the rest of the body. For example, any age-related impairment in hepatic drug and xenobiotic detoxification could partly explain the susceptibility of elderly persons to adverse drug reactions or illnesses with toxic etiology. 5 In vivo, the hepatic clearance of many drugs is reduced in elderly persons. Traditional theories have attempted to attribute this to age-related reduction of liver mass and blood flow. 6 However, in a recent review, 5 we noted that there appears to be selective reduction of the clearance of drugs that undergo phase I metabolism, associated with preservation of the clearance of drugs that undergo phase II metabolism. Even more puzzling, the in vitro activities of phase I enzymes are maintained into old age. 7 Because these paradoxes cannot be attributed to changes in blood flow and liver mass alone, we suggested an explanation based on oxygen supply, as the activities of phase I enzymes are highly oxygen-dependent because they require oxygen as a substrate. 8 We hypothesized the development of a barrier to oxygen diffusion, leading to functional intracellular hypoxia in the hepatocytes of the aging liver. This provides a plausible mechanism for i...

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“…It has been successfully used to assess the metabolic state of a variety of tissues under various conditions. [19][20][21] The ATP/DNA ratio suffers similar limitations, but DNA does not degrade as quickly in dead cells as either ATP or ADP. Because of this profound difference in the kinetics of degradation of DNA under conditions of stress, the ATP/DNA ratio permits the inclusion of dead cells into a viability estimate once the apoptotic process is fully executed.…”

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confidence: 99%

The ATP/DNA Ratio Is a Better Indicator of Islet Cell Viability Than the ADP/ATP Ratio

Suszynski¹,

Wildey²,

Falde³

et al. 2008

Transplantation Proceedings

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Real-time, accurate assessment of islet viability is critical for avoiding transplantation of nontherapeutic preparations. Measurements of the intracellular ADP/ATP ratio have been recently proposed as useful prospective estimates of islet cell viability and potency. However, dead cells may be rapidly depleted of both ATP and ADP, which would render the ratio incapable of accounting for dead cells. Since the DNA of dead cells is expected to remain stable over prolonged periods of time (days), we hypothesized that use of the ATP/DNA ratio would take into account dead cells and may be a better indicator of islet cell viability than the ADP/ATP ratio. We tested this hypothesis using mixtures of healthy and lethally heat-treated (HT) rat insulinoma cells and human islets. Measurements of ATP/DNA and ADP/ATP from the known mixtures of healthy and HT cells and islets were used to evaluate how well these parameters correlated with viability. The results indicated that ATP and ADP were rapidly (within 1 hour) depleted in HT cells. The fraction of HT cells in a mixture correlated linearly with the ATP/DNA ratio, whereas the ADP/ADP ratio was highly scattered, remaining effectively unchanged. Despite similar limitations in both ADP/ADP and ATP/ DNA ratios, in that ATP levels may fluctuate significantly and reversibly with metabolic stress, the results indicated that ATP/DNA was a better measure of islet viability than the ADP/ATP ratio.Islet cell transplantation is emerging as a promising therapy for the treatment of type 1 diabetes. [1][2][3][4][5] Despite recent advances, the transplantation of islets poses a unique challenge with respect to achieving a consistent clinical outcome. Part of this challenge is being able to reliably and rapidly assess clinical islet quality through the quantification of viability and function before transplantation. Current viability assays are limited in their ability to accurately predict transplantation outcomes in vivo. 6 Consequently, to improve the clinical islet transplantation outcomes, it is imperative to develop more accurate viability assays.A proposed method to assess islet viability and potency before transplantation is quantification of the ADP/ATP ratio. 6 -10 This ratio has been specifically applied in discriminating islet preparations that are suitable for clinical transplantation from those that are not. 6 However, this application may be problematic under certain conditions. Intracellular ADP and ATP levels fluctuate rapidly because these high-energy phosphate molecules are rapidly produced and consumed in many intracellular biochemical reactions. It is widely known that viable cells turn over entire ATP stores on the order of minutes, and that dead cells are incapable of replenishing To better account for dead cells and to more accurately assess the viability of an islet preparation, we suggest the use of an ATP/DNA ratio. DNA does not degrade as rapidly as ADP or ATP in a dead cell. Therefore, using direct measurements of DNA, dead cells in an islet preparation...

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31P and1H NMR spectroscopic studies of liver extracts of carbon tetrachloride-treated rats

Cited by 31 publications

References 30 publications

Biochemical metabolic changes assessed by³¹P magnetic resonance spectroscopy after radiation-induced hepatic injury in rabbits

Biochemical metabolic changes assessed by³¹P magnetic resonance spectroscopy after radiation-induced hepatic injury in rabbits

Pseudocapillarization and associated energy limitation in the aged rat liver

The ATP/DNA Ratio Is a Better Indicator of Islet Cell Viability Than the ADP/ATP Ratio

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31P and1H NMR spectroscopic studies of liver extracts of carbon tetrachloride-treated rats

Cited by 31 publications

References 30 publications

Biochemical metabolic changes assessed by31P magnetic resonance spectroscopy after radiation-induced hepatic injury in rabbits

Biochemical metabolic changes assessed by31P magnetic resonance spectroscopy after radiation-induced hepatic injury in rabbits

Pseudocapillarization and associated energy limitation in the aged rat liver

The ATP/DNA Ratio Is a Better Indicator of Islet Cell Viability Than the ADP/ATP Ratio

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Biochemical metabolic changes assessed by³¹P magnetic resonance spectroscopy after radiation-induced hepatic injury in rabbits

Biochemical metabolic changes assessed by³¹P magnetic resonance spectroscopy after radiation-induced hepatic injury in rabbits