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Neuroendocrinology Letters incl. Psychoneuroimmunology & Chronobiology

NEUROENDOCRINOLOGY LETTERS
including Psychoneuroimmunology, Neuro
psychopharmacology,
Reproductive Medicine, Chronobiology
and Human Ethology
ISSN 0172–780X

NEL VOL. 22 No. 6

Original Article

Melatonin reduces apoptotic rate induced by aflatoxin B1 in rat liver

2001; 22:417-426
pii: NEL220601A01

full text pdf (273)


Aflatoxin B1 Induces Apoptosis in Rat Liver : Protective Effect of Melatonin

by Abdel-Raheim M. A. Meki, Sary Kh. Abdel-Ghaffar
& Ibrahim El-Gibaly

Keywords:
Aflatoxin B1, liver, apoptosis, histopathology, melatonin, oxidative stress, antioxidant, Rat

Submitted: September 15, 2001
Accepted: November 17, 2001

OBJECTIVES: A study of liver apoptosis after aflatoxin B1 (AFB1) administration and the effect of melatonin (MEL) was investigated in male rats.

METHODS: Five groups of 15 rats each were used : controls, MEL Soln-treated rats (MEL dose,5 mg/Kg body wt), AFB1-treated rats (50 mg/Kg body wt), MEL Soln+AFB1-treated rats, and MEL micro-capsules (MEL-MC) + AFB1-treated rats. After 8 weeks of treatment, biochemical measurements in liver homogenates and histopathological examination of liver sections of different groups using light and transmission electron microscope were done. The caspase-3 enzyme activity, apoptotic marker, was determined in liver tissues. Because hepatic antioxidants represent the major defence against toxic liver injury, and they act as anti-apoptosis. So, the levels of glutathione (GSH) and zinc (Zn) and the enzyme activities of glutathione reductase (GR), glutathione peroxidase (GSPx) and glutathione-S-transferase (GST) were determined. In addition, the levels of malondialdehyde (MDA), a lipid peroxidation product, and nitric oxide (NO) levels were measured.

RESULTS: The levels of caspase-3 activities in AFB1 group were significantly higher than control group. The apoptosis was associated with degenerative and necrotic changes in the hepatocytes. Concomitantly, the levels of MDA and NO in liver tissues were significantly increased while the levels of GSH, Zn and enzyme activities of GSPx and GR in liver tissues were significantly decreased in AFB1 group compared to their levels in controls. Caspase-3 activity was positively correlated with MDA while negatively correlated with GSH, GSPx and GR in rat livers treated with AFB1. The apoptotic rate was significantly reduced when MEL was co-administrated with AFB1. In rats received MEL with AFB1, the levels of MDA and NO in liver tissues were significantly reduced while GSH and Zn levels and GSPx, GR and GST activities were significantly increased compared to AFB1 group. When MEL-MC co-administrated with AFB1 appeared more effective in reduction of apoptotic rate as detected by decline of caspase-3 activities (inhibition 66.82%) and confirmed by histopathology.

CONCLUSION: AFB1 can lead to direct or indirect caspase-3 activation and consequently to apoptosis in rat liver. MEL treatment of rats could enhance hepatic antioxidant/detoxification system which consequently reduce the apoptotic rate and the necrobiotic changes in the liver. MEL-MC exhibited an efficient protective effect against AFB1. Thus, clinical application of MEL as therapy should be considered in cases of aflatoxicosis.

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Copyright  Neuroendocrinology Letters 2001
All rights reserved. No part may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or ortherwise, without prior written permission from the Editor-in-Chief.