Modification of acute and chronic liver damage by thiazolidine compounds
Tóm tắt
As high sulfhydril levels were shown to reduce the action of agents causing tissue-injury, increasing glutathion concentrations may have cytoprotective potential. In this study the hepatoprotective effects of several derivatives of 4-carboxy-5,5-dimethyl thiazolidine, a modulator of glutathion metabolism were studied in rat liver damaged with CC14. It was found that 4(S) carboxy 5,5-dimethyl-2 (5′-nitro-2-furyl) thiazolidine (dimethyl-thiazolidine-nitrofuran: DTNF) had the most significant hepatoprotective action; therefore it was subjected to detailed investigation in various models for acute and chronic liver injury. This compound was shown to ameliorate allylalcohol induced liver injury in rats, galactosamine induced hepatitis of mice and CC14 induced chronic liver damage in rats. Our study on protein synthesis in primary hepatocyte suspension culture showed that cell injury induced by CCI4 could be reduced in the presence of this thiazolidine compound.
Tài liệu tham khảo
Biggs HG, Eriksen JM and Moerehead WR: A manual colorimetric assay of triglycerides in serum. Clin Chem 21: 437–441, 1975.
Bognar R, Györgydrák Z, Szidgyi L, Sánder P and Radies L: Hetcrocyclische Verbindungen aus Zuckern. XI Ringsehlußreaktion von D-Penicillamim mit 2. 3 4. 5-Tetra-O-ace-tyl-aldehydo-l arabinose: 13C-NMR Spektren von 2 Poly acetoxyalkythiazolidm-4-carbon-säurederiyaten. Justus Liebigs Annalen der Chemie 747: 701–707, 1979.
Bognár R, Somogyi I and Györgydeák Z.: Heterocxclische Verbindungen aus Zuckern. III Substituirte Thiazolidine durch Reaktion von L.-Cystein mit Monosaechariden. Justus Liebigs Ann Chem 738: 68–78, 1970.
Divald A, Jeney A, O-Nagy J, Timár F and Lapis K.: Modification of the inhibitory effects of CCI, on phospholipid and protein biosynthesis by prostacyclin. Biochem Pharmacol 40: 1477–1483, 1990.
Györgydeák Z, Kajtár-Peredy M, Kajtár J and Kajiár M: Synthese und chiroptische Eigenschaften von N-Acctyl–2- any 1–4-thiazolidinearbonsäuren. Justus Liebigs Ann Chem 756: 927–934, 1987.
Györgydeák Z, Kajtar M and kajlár-Peredy M: Darstellung und Charakterisierung von diastereomeren (4S)-3-acelyl-2-aryl-5.5-diimethyl-4 thiazolidincarbonsäuren Justus. Liehigs Ann Chem 281–266, 1990.
Handel E: Fstimation ol glycogen in small amounts of tissue. Anal Biochem 11: 256–265, 1965.
Nagasawa HT, Goon DJW, Zera RT and Yuzon DL.: Prodrugs of L-eysteine as liver-protective agents. 2(RS)-Methylthiazo lidine-4(R)-carboxylie acid a latent cysteine. J Med Chem 25: 489, 1979.
Nagasawa HT, Goon DJW, Muldoon Ed and Zera RT: 2-substituted thiazolidine-4(R)-carboxylic acids as prodrugs of I-cysteinc Protection of mice against acctaminophen hepat-toxicity. J Med Chem 27:591–596, 1984.
Reitman S and Franhel S: A colorimetric method for the determination of serum glutamic exalacetie and glutamic pyruyic transaminases. Am J Clin Pathol 28: 56–63, 1957.
Williamson JM, Bortteher B and Meister A: Intracellular cysteine delivery system that protects against toxicity by promoting glutathione synthesis. Proc Natl Acad Sci 79: 6246–6249, 1982.
Woessner JF: The determination of hydroxiproline in tissue and protein samples containing small portions of this amino acid. Arch Biochem Biophys 93: 440–447, 1961.