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Aflatoxin B1 induces apoptosis in rat liver: protective effect of melatonin.

Abstract

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 microg/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 co-administrated with AFB1. In rats which 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.

Authors+Show Affiliations

,

Biochemistry Department, Faculty of Medicine, Assiut University, Assiut, Egypt. Meki202000@Yahoomail.com.

,

Source

Neuro endocrinology letters 22:6 2001 Dec pg 417-26

MeSH

Aflatoxin B1
Animals
Antioxidants
Apoptosis
Caspase 3
Caspases
Glutathione
Glutathione Peroxidase
Glutathione Reductase
Glutathione Transferase
Lipid Peroxidation
Liver
Male
Melatonin
Nitric Oxide
Oxidative Stress
Rats
Rats, Sprague-Dawley
Zinc

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11781538

Citation

TY - JOUR T1 - Aflatoxin B1 induces apoptosis in rat liver: protective effect of melatonin. AU - Meki,A R, AU - Abdel-Ghaffar,S K, AU - El-Gibaly,I, PY - 2002/1/10/pubmed PY - 2002/2/15/medline PY - 2001/Sep/15/received PY - 2001/Nov/17/accepted PY - 2002/1/10/entrez SP - 417 EP - 26 JF - Neuro endocrinology letters JO - Neuro Endocrinol. Lett. VL - 22 IS - 6 N2 - 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 microg/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 co-administrated with AFB1. In rats which 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. SN - 0172-780X UR - https://www.unboundmedicine.com/medline/citation/11781538/Aflatoxin_B1_induces_apoptosis_in_rat_liver:_protective_effect_of_melatonin_ L2 - http://www.labome.org//expert/faculty/meki/abdel-raheem-a-m-meki-266557.html ER -