| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Departamento de Fisiología, Instituto de Biotecnología, Universidad de Granada, Spain;
Departamento de Bioquímica Médica y Biología Molecular, Facultad de Medicina, Universidad de Sevilla, Spain
1Correspondence: Departamento de Fisiología, Facultad de Medicina, Avda. de Madrid 11, E-18012 Granada, Spain. E-mail: dacuna{at}goliat.ugr.es
We evaluated the role of melatonin in endotoxemia caused by
lipopolysaccharide (LPS) in unanesthetized
rats. The expression of inducible isoform of nitric oxide synthase
(iNOS) and the increase in the oxidative stress seem to be responsible
for the failure of lungs, liver, and kidneys in endotoxemia. Bacterial
LPS (10 mg/kg b.w) was i.v. injected 6 h before rats were killed
and melatonin (10–60 mg/kg b.w.) was i.p. injected before and/or after
LPS. Endotoxemia was associated with a significant rise in the serum
levels of aspartate and alanine aminotransferases,
-glutamyl-transferase, alkaline phosphatase, creatinine, urea, and
uric acid, and hence liver and renal dysfunction. LPS also increased
serum levels of cholesterol and triglycerides and reduced glucose
levels. Melatonin administration counteracted these organ and metabolic
alterations at doses ranging between 20 and 60 mg/kg b.w. Melatonin
significantly decreased lung lipid peroxidation and counteracted the
LPS-induced NO levels in lungs and liver. Our results also show an
inhibition of iNOS activity in rat lungs by melatonin in a
dose-dependent manner. Expression of iNOS mRNA in lungs and liver was
significantly decreased by melatonin (60 mg/kg b.w., 58–65%). We
conclude that melatonin inhibits NO production mainly by inhibition of
iNOS expression. The inhibition of NO levels may account for the
protection of the indoleamine against LPS-induced endotoxemia in
rats.—Crespo, E., Macías, M., Pozo, D., Escames, G.,
Martín, M., Vives, F., Guerrero, J. M.,
Acuña-Castroviejo, D. Melatonin inhibits expression of the
inducible NO synthase II in liver and lung and prevents endotoxemia in
lipopolysaccharide-induced multiple organ dysfunction syndrome in rats.
Key Words: iNOS • endotoxic shock • genomic effects
This article has been cited by other articles:
|
|
 |
|
  W.-G. Deng, S.-T. Tang, H.-P. Tseng, and K. K. Wu Melatonin suppresses macrophage cyclooxygenase-2 and inducible nitric oxide synthase expression by inhibiting p52 acetylation and binding Blood, July 15, 2006; 108(2): 518 - 524. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Pei, S. F. Pang, and R. T. F. Cheung Administration of Melatonin After Onset of Ischemia Reduces the Volume of Cerebral Infarction in a Rat Middle Cerebral Artery Occlusion Stroke Model Stroke, March 1, 2003; 34(3): 770 - 775. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Matsuzaki, M. Kuwamura, R. Yamaji, H. Inui, and Y. Nakano Inflammatory Responses to Lipopolysaccharide Are Suppressed in 40% Energy-Restricted Mice J. Nutr., August 1, 2001; 131(8): 2139 - 2144. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. van der Loo, R. Labugger, J. N. Skepper, M. Bachschmid, J. Kilo, J. M. Powell, M. Palacios-Callender, J. D. Erusalimsky, T. Quaschning, T. Malinski, et al. Enhanced Peroxynitrite Formation Is Associated with Vascular Aging J. Exp. Med., December 11, 2000; 192(12): 1731 - 1744. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. León, M. Macías, G. Escames, E. Camacho, H. Khaldy, M. Martín, A. Espinosa, M. A. Gallo, and D. Acuña-Castroviejo Structure-Related Inhibition of Calmodulin-Dependent Neuronal Nitric-Oxide Synthase Activity by Melatonin and Synthetic Kynurenines Mol. Pharmacol., November 1, 2000; 58(5): 967 - 975. [Abstract] [Full Text]
|
|
|
|
 |
|
 C. Zhang, L. M. Walker, J. A. Hinson, and P. R. Mayeux Oxidant Stress in Rat Liver after Lipopolysaccharide Administration: Effect of Inducible Nitric-Oxide Synthase Inhibition J. Pharmacol. Exp. Ther., June 1, 2000; 293(3): 968 - 972. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
