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Aflatoxin B1 induces apoptosis in rat liver: protective effect of melatonin
A R Meki1, S K Abdel-Ghaffar, I El-Gibaly
1Biochemistry Department, Faculty of Medicine, Assiut University, Assiut, Egypt. Meki202000@Yahoomail.com.
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.
Insights
Aflatoxin B1 (AFB1) induces liver apoptosis in rats, but melatonin (MEL) treatment, especially in micro-capsule form (MEL-MC), protects against this damage by boosting antioxidant defenses.
Area of Science:
- Hepatology and Toxicology
- Molecular Biology and Biochemistry
Background:
- Aflatoxin B1 (AFB1) is a potent hepatotoxin known to induce oxidative stress and apoptosis in liver cells.
- Melatonin (MEL) is a hormone with antioxidant and anti-apoptotic properties, potentially offering protection against toxic insults.
Purpose of the Study:
- To investigate the induction of liver apoptosis by AFB1 in male rats.
- To evaluate the protective effects of melatonin, administered as a solution (MEL) or micro-capsules (MEL-MC), against AFB1-induced hepatotoxicity.
Main Methods:
- Male rats were divided into five groups: control, MEL, AFB1, MEL+AFB1, and MEL-MC+AFB1.
- Liver tissues were analyzed after 8 weeks for biochemical markers of apoptosis (caspase-3 activity), oxidative stress (malondialdehyde, nitric oxide), and antioxidant status (glutathione, zinc, glutathione reductase, glutathione peroxidase, glutathione-S-transferase).
- Histopathological examination using light and transmission electron microscopy was performed.
Main Results:
- AFB1 administration significantly increased caspase-3 activity, malondialdehyde, and nitric oxide levels, while decreasing glutathione, zinc, glutathione peroxidase, and glutathione reductase levels in rat livers.
- AFB1 induced significant degenerative and necrotic changes in hepatocytes.
- Melatonin treatment (both MEL and MEL-MC) significantly attenuated AFB1-induced apoptosis and oxidative stress, with MEL-MC showing a more pronounced protective effect (66.82% inhibition of caspase-3 activity).
Conclusions:
- Aflatoxin B1 triggers liver apoptosis via caspase-3 activation, leading to significant oxidative damage.
- Melatonin enhances the hepatic antioxidant and detoxification systems, effectively reducing AFB1-induced apoptosis and necrobiotic changes.
- Melatonin micro-capsules demonstrate superior efficacy in protecting the liver against AFB1 toxicity, suggesting potential therapeutic applications in aflatoxicosis.
