Abstract |
An amphiphilic alpha-phenyl-N-(tert-butyl) nitrone (PBN) derivative, N-{[4-(lactobionamido)methyl]benzylidene}-1,1-dimethyl-2-(octylsulfanyl) ethylamine N- oxide (LPBNSH), newly synthesized from its original form PBN in hopes of clinical use, was intraperitoneally administered to Long-Evans Cinnamon (LEC) rats every 2 days at the concentrations of 0.1, 0.5, 1.0, and 2.0 mg/kg. We found that LPBNSH protected against copper-induced hepatitis with jaundice in LEC rats at concentrations of 0.1 and 0.5 mg/kg, which were extremely low compared with that of PBN. It also effectively prevented the loss of body weight, reduced the death rate, and suppressed the increase in serum aspartate aminotransferase and alanine aminotransferase values arising from fulminant hepatitis with jaundice at the same concentrations. Similar results were observed when PBN was administered at the concentration of 150 mg/kg. Immunohistochemical analysis of 8-hydroxy-2'-deoxyguanosine and measurement of thiobarbituric acid-reactive substances in the liver showed that LPBNSH largely suppressed the formation of these oxidative products at same concentrations. No difference in the abnormal accumulation of copper in the liver between the LPBNSH administered and control groups was observed. From these results, it was concluded that LPBNSH exhibited liver-protective effects against fulminant hepatitis with jaundice at ca. 1/1000, 500 the molar concentration of PBN and, therefore, was clinically promising.
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Authors | Taketoshi Asanuma, Hironobu Yasui, Osamu Inanami, Kenji Waki, Momoko Takahashi, Daisuke Iizuka, Taketo Uemura, Grégory Durand, Ange Polidori, Yasuhiro Kon, Bernard Pucci, Mikinori Kuwabara |
Journal | Chemistry & biodiversity
(Chem Biodivers)
Vol. 4
Issue 9
Pg. 2253-67
(Sep 2007)
ISSN: 1612-1880 [Electronic] Switzerland |
PMID | 17886845
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antioxidants
- Cyclic N-Oxides
- Disaccharides
- Imines
- N-((4-(lactobionamido)methyl)benzylidene)-1,1-dimethyl-2-(octylsulfanyl)ethylamine N-oxide
- Thiobarbituric Acid Reactive Substances
- phenyl-N-tert-butylnitrone
- Copper
- 8-Hydroxy-2'-Deoxyguanosine
- Deoxyguanosine
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Topics |
- 8-Hydroxy-2'-Deoxyguanosine
- Animals
- Antioxidants
(therapeutic use)
- Chemical and Drug Induced Liver Injury
(pathology, prevention & control)
- Copper
(analysis, toxicity)
- Cyclic N-Oxides
(therapeutic use)
- Deoxyguanosine
(analogs & derivatives, analysis)
- Disaccharides
(therapeutic use)
- Imines
(therapeutic use)
- Immunohistochemistry
- Liver
(chemistry, pathology)
- Liver Failure, Acute
(chemically induced, pathology, prevention & control)
- Male
- Rats
- Rats, Inbred LEC
- Thiobarbituric Acid Reactive Substances
(analysis)
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