Potential of Nitroimidazoles as Markers of Hypoxia in Heart

Wl, Rumsey; Patel, B. K.; Kuczynski, Bruce L.; Rk, Narra; Yw, Chan; Ke, Linder; J, Cyr; Raju, Natarajan; Ramalingam, Kondareddiar; Ad, Nunn

doi:10.1007/978-1-4615-2468-7_35

Cited by 9 publications

(2 citation statements)

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“…Still nitroimidazole structurefunction relationship of hypoxia, radiosensitization and cytotoxicity remain less understood perhaps due to its low sensitivity to clinical investigations and available enzyme alterations at the very late necrotic stage [16][17][18][19][20][21][22][23][24]. However, nitroimidazole cytotoxicity was reported continuously in last three decades indicating altered enzymes, nitric oxide production, cytokines, oxygen depletion (hypoxia) and immunoactive substance release from both hepatic infections and cancer tumor tissues [25][26][27][28][29][30]. Still, studies do not establish the acceptability of growing popularity of nitroimidazole in tumor monitoring and treatment as risk free if nitroimidazole can induce tissue regeneration after hepatic infections or oxygen starved tumors [32].…”

Section: Introductionmentioning

confidence: 99%

The Hepatocellular Hypoxia Criteria:2’Nitroimidazole Effect on Hepatocyte Carbohydrate Metabolizing Enzymes

Sharma

2008

Nat Prec

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Aim: to understand the 2'-nitroimidazole induced hypoxia and liver cell interaction, we proposed a "Hapatocellular Hypoxia Criteria". Hypothesis: The nitroimidazole induced metabolic energy loss and oxygen depletion (hypoxia) in liver cell mitochondria causes the phagocytosis. Based on it, ten control subjects with 2'-nitroimidazole therapy were studied for their carbohydrate metabolizing enzymes in serum and hepatocellular enzymes in liver biopsy tissues. Materials and Methods: Proven ten control subjects were studied for hypoxia by enzyme assays. The 2'nitroimidazole treated paired ten subjects were studied for hypoxia using enzyme assays and hepatocellular cytomorphology by electron microscopy. Results and Discussion: Out of ten subjects on 2'-nitroimidazole, nine showed elevated carbohydrate metabolizing and lysosomal enzyme levels in serum. The enzymes glucokinase (in 80% samples), aldolase (in 80% samples), phosphofructokinase (in 80% samples), malate dehydrogenase (in 75% samples), isocitrate dehydrogenase (ICDH) (in 60% patients) were elevated while succinate dehydrogenase and lactate dehydrogenase (LDH) levels remained unaltered. Lysosomal enzymes-glucuronidase, alkaline phosphatase, acid phosphatase, β showed enhanced levels in the serum samples. In control ten liver biopsies, the hepatocytes and Kupffer cell preparations showed altered enzyme levels. Hepatocytes showed lowered glucokinase (in 80%), LDH (in 80%), and higher content of aldolase (in 80%), pyruvate kinase (in 100%), malate dehydrogenase (in 80%), ICDH (in 80%), citrate dehydrogenase (in 70%), phosphogluconate dehydrogenase (in 80%). Kupffer cells showed higher enzyme levels of-β glucuroronidase (in 80%), leucine aminopeptidase (in 70%), acid phosphatase (in 80%) and aryl sulphatase (in 88%). In these 10 biopsy samples from subjects on 2'-nitronidazole clinical trial, the electron microscopy cytomorphology observations showed swollen bizarre mitochondria, proliferative endoplasmic reticulum, and anisonucleosis after 2'-Nitroimidazole effect in liver cell damage. Conclusion: The proposed "Hepatocellular Hypoxia Criteria" served to define origin of liver hypoxia and showed altered hepatic enzyme activities with active phagocytosis and cytotoxicity in subjects after 2'-nitroimidazole treatment. The study suggests the enzyme

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Section: Introductionmentioning

confidence: 99%

The Hepatocellular Hypoxia Criteria:2’Nitroimidazole Effect on Hepatocyte Carbohydrate Metabolizing Enzymes

Sharma

2008

Nat Prec

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“…Source: Thesis author BMS 181321 (Figure 19) was the first 99m Tc-labelled 2-nitroimidazole to be widely studied for imaging [155], and several experimental studies have evaluated the use of BMS 181321 for the detection of ischemic and hypoxic myocardium [156][157][158][159]. Ballinger et al showed selective accumulation in hypoxic cells in vitro and in vivo but concluded that BMS 18 1321 was not optimal for tumor hypoxia imaging because of in vitro and in vivo instabilities and a high partition coefficient, resulting in slow clearance from the blood and high background levels in normal tissues [160].…”

Section: Source: Thesis Authormentioning

confidence: 99%