[해외논문]
Characterization of the protective effects of melatonin and related indoles against α-naphthylisothiocyanate-induced liver injury in rats
Journal of cellular biochemistry ,
v.80 no.4 ,
2001년, pp.461 - 470
Calvo, J.R.
(Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas 78229)
,
Reiter, R.J.
(Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas 78229)
,
García, J.J.
(Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas 78229)
,
Ortiz, G.G.
(Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas 78229)
,
Tan, D.X.
(Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas 78229)
,
Karbownik, M.
(Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas 78229)
The protective effect of melatonin, 6-hydroxymelatonin and N-acetylserotonin against α-naphthylisothiocyanate (ANIT)-induced liver injury was investigated and compared in rats injected once with the hepatotoxicant (75 mg/kg body weight). In rats injected with ANIT alone, liver injury with chol...
The protective effect of melatonin, 6-hydroxymelatonin and N-acetylserotonin against α-naphthylisothiocyanate (ANIT)-induced liver injury was investigated and compared in rats injected once with the hepatotoxicant (75 mg/kg body weight). In rats injected with ANIT alone, liver injury with cholestasis developed within 24 h, as indicated by both serum levels of alanine aminotransferase (SGPT) and aspartic acid aminotransferase (SGOT) activities and serum total bilirubin concentration. The administration of melatonin or 6-hydroxymelatonin (10 mg/kg body weight) to ANIT-injected rats reduced significantly the serum levels of both SGPT and SGOT and the serum total bilirubin concentration. For all hepatic biochemical markers, melatonin was more effective that 6-hydroxymelatonin. By comparison, the administration of N-acetylserotonin (10 mg/kg body weight) to ANIT-injected rats did not reduce the serum levels of either hepatic enzymes or the serum total bilirubin concentration. In ANIT-injected rats, hepatic lipid peroxidation (LPO) was significantly higher than in control animals and this increase was significantly reduced by either melatonin, 6-hydroxymelatonin or N-acetylserotonin. Furthermore, ANIT treatment caused a significant reduction in liver microsomal membrane fluidity and this reduction was completely reversed by the three indoles. The liver from ANIT-injected rats showed several histopathological alterations; above all there was an acute infiltration of polymorphonuclear neutrophils and an increase in the number of apparent apoptotic hepatocytes. The concurrent administration of melatonin reduced the severity of all morphological alterations, specially the neutrophil infiltration and the number of presumed apoptotic cells. On the contrary, the administration of 6-hydroxymelatonin or N-acetylserotonin did not provide any protective effect in terms of the histopathological alterations. These results indicate that melatonin protects against ANIT-induced liver injury with cholestasis in rats, and suggests that this protective effect is likely due to its antioxidant properties and above all to its capacity to inhibit liver neutrophil infiltration, a critical factor in the pathogenesis of ANIT-induced liver injury. 6-hydroxymelatonin, although able to provide partial protection against the ANIT-induced hepatic injury, probably through its antioxidant properties by mechanisms that are unclear, was unable to reduce neutrophil infiltration. Finally, N-acetylserotonin in the experimental conditions of this study, only exhibited some antioxidant protection but had no protective effect against ANIT-induced hepatic damage. J. Cell. Biochem. 80:461–470, 2001. © 2001 Wiley-Liss, Inc.
The protective effect of melatonin, 6-hydroxymelatonin and N-acetylserotonin against α-naphthylisothiocyanate (ANIT)-induced liver injury was investigated and compared in rats injected once with the hepatotoxicant (75 mg/kg body weight). In rats injected with ANIT alone, liver injury with cholestasis developed within 24 h, as indicated by both serum levels of alanine aminotransferase (SGPT) and aspartic acid aminotransferase (SGOT) activities and serum total bilirubin concentration. The administration of melatonin or 6-hydroxymelatonin (10 mg/kg body weight) to ANIT-injected rats reduced significantly the serum levels of both SGPT and SGOT and the serum total bilirubin concentration. For all hepatic biochemical markers, melatonin was more effective that 6-hydroxymelatonin. By comparison, the administration of N-acetylserotonin (10 mg/kg body weight) to ANIT-injected rats did not reduce the serum levels of either hepatic enzymes or the serum total bilirubin concentration. In ANIT-injected rats, hepatic lipid peroxidation (LPO) was significantly higher than in control animals and this increase was significantly reduced by either melatonin, 6-hydroxymelatonin or N-acetylserotonin. Furthermore, ANIT treatment caused a significant reduction in liver microsomal membrane fluidity and this reduction was completely reversed by the three indoles. The liver from ANIT-injected rats showed several histopathological alterations; above all there was an acute infiltration of polymorphonuclear neutrophils and an increase in the number of apparent apoptotic hepatocytes. The concurrent administration of melatonin reduced the severity of all morphological alterations, specially the neutrophil infiltration and the number of presumed apoptotic cells. On the contrary, the administration of 6-hydroxymelatonin or N-acetylserotonin did not provide any protective effect in terms of the histopathological alterations. These results indicate that melatonin protects against ANIT-induced liver injury with cholestasis in rats, and suggests that this protective effect is likely due to its antioxidant properties and above all to its capacity to inhibit liver neutrophil infiltration, a critical factor in the pathogenesis of ANIT-induced liver injury. 6-hydroxymelatonin, although able to provide partial protection against the ANIT-induced hepatic injury, probably through its antioxidant properties by mechanisms that are unclear, was unable to reduce neutrophil infiltration. Finally, N-acetylserotonin in the experimental conditions of this study, only exhibited some antioxidant protection but had no protective effect against ANIT-induced hepatic damage. J. Cell. Biochem. 80:461–470, 2001. © 2001 Wiley-Liss, Inc.
Keyword
참고문헌 (41)
Anal Biochem Bradford 72 248 1976 10.1016/0003-2697(76)90527-3
Arch Toxicol Calcamuggi 66 126 1992 10.1007/BF02342506
Neuroscience Carneiro 82 293 1998 10.1016/S0306-4522(97)00262-5
Hepatology Casini 25 361 1997 10.1002/hep.510250218
Toxicol Appl Pharmacol Connolly 93 208 1988 10.1016/0041-008X(88)90121-4
Arch Biochem Biophys Curtis 235 644 1984 10.1016/0003-9861(84)90239-X
J Pineal Res Cuzzocrea 23 106 1997 10.1111/j.1600-079X.1997.tb00342.x
J Pineal Res Chan 20 187 1996 10.1111/j.1600-079X.1996.tb00257.x
J Pharmacol Exp Ther Dahm 256 412 1991
Toxicol Appl Pharmacol Driscoll 119 306 1993 10.1006/taap.1993.1074
FEBS Lett Eichenberger 408 297 1982
Shock El-Sokkary 12 402 1999a 10.1097/00024382-199911000-00009
Alcohol El-Sokkary 34 842 1999b 10.1093/alcalc/34.6.842
Meth Enzymol Esterbauer 186 407 1990 10.1016/0076-6879(90)86134-H
FEBS Lett García 408 297 1997 10.1016/S0014-5793(97)00447-X
J Membrane Biol García 162 59 1998 10.1007/s002329900342
J Immunol García-Mauriño 159 574 1997 10.4049/jimmunol.159.2.574
Am J Pathol Goldfarb 40 685 1962
Biol Signals Hara 6 90 1997 10.1159/000109113
Toxicol Appl Pharmacol Hill 148 169 1998 10.1006/taap.1997.8314
Toxicol Sci Hill 47 118 1999 10.1093/toxsci/47.1.118
Biochem Pharmacol Jean 50 1469 1995 10.1016/0006-2952(95)02051-9
Toxicol Lett Kongo 105 103 1999 10.1016/S0378-4274(98)00397-X
Life Sci Longoni 62 853 1998 10.1016/S0024-3205(98)00002-2
Free Radic Biol Med Matuszak 23 367 1997 10.1016/S0891-5849(96)00614-4
J Pineal Res Montilla 28 143 2000 10.1034/j.1600-079X.2001.280303.x
Proc Assoc Am Physicians Morland 109 372 1997
J Trad Med (Wakan Iyakugaku Zasshi) Ohta 14 143 1997
J Pineal Res Ohta 29 15 2000a 10.1034/j.1600-079X.2000.290103.x
J Pineal Res Ohta 28 119 2000b 10.1034/j.1600-079X.2001.280208.x
Int J Neurosci Oxenkrug 77 237 1994 10.3109/00207459408986034
Pharmacol Rev Plaa 28 207 1977
Adv Exp Med Bio Reiter 398 307 1996 10.1007/978-1-4613-0381-7_48
Hepatology Reynoso-Paz 30 351 1999 10.1002/hep.510300218
Drug Metab Rev Roth 29 153 1997 10.3109/03602539709037578
Lab Invest Roth 62 736 1990
Kidney Int Schmouder 44 43 1993 10.1038/ki.1993.211
Eur J Pharmacol Sewerynek 283 327 1995 10.1016/0926-6917(95)90052-7
Hepatogastroenterology Sewerynek 43 898 1996
Life Sci Tan 65 2523 1999 10.1016/S0024-3205(99)00519-6
FEBS Lett Wölfler 449 206 1999 10.1016/S0014-5793(99)00435-4
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