الفهرس 
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Abstract
Caffeine is a natural stimulatory compound present in tea and coffee. Excessive amounts of caffeine can adversely affect the body through significant toxic effects including anxiety, delirium, headache, insomnia, nervousness, dehydration, hyperglycemia, and arrhythmia. In addition, high concentrations of caffeine induce cellular apoptosis, cell death, and can cause indirect DNA damage because of the oxidative stress that it can cause.
The current study aimed to investigate the protective effects of taurine and melatonin against caffeine induced brain and liver damage in rats.
The adult Wistar rats of this study were allocated into six groups (six rats for each) as follow:
group I (Control): Rats received distilled water via oral gavage for 28 days. group II: Rats received 20 mg/kg melatonin dissolved in distilled water via oral gavage daily for 28 days.
group III: Rats received 50 mg/kg taurine dissolved in distilled water via oral gavage daily for 28 days.
group IV: Rats received 50 mg/kg caffeine dissolved in distilled water via oral gavage daily for 28 days.
group V: Rats received melatonin as described in group II in concomitant with caffeine as described in group IV.
group VI: Rats received taurine as described in group III in concomitant with caffeine as described in group IV.
In the present study, caffeine-administered rats showed a significant liver damage manifested by the increased serum ALT, AST, ALP and the lowered albumin level. The treatment of caffeine-administered rats with melatonin and taurine led to marked improvements in these liver function parameters in serum.
Concerning brain and liver oxidative stress, the elevated MDA levels were potentially decreased in the caffeine-administered rats due to melatonin and taurine administration. Regarding antioxidant defense system, the depleted SOD activity as well as GSH content of caffeine-administered rats were potentially increased as a result melatonin and taurine treatments.
The obtained data also revealed a significant increase in dopamine and norepinephrine levels in caffeine-administered rats. The treatment of caffeineadministered rats with melatonin and taurine successfully ameliorated these changes.
Regarding the DNA damage in liver and brain, comet assay results showed an increased DNA damage and tail percentage in caffeine-administered rats. The treatment with melatonin and taurine ameliorated these alterations.
The administration of caffeine up-regulated Bax and p53 gene and protein expression, and down-regulated Bcl-2 expression. The treatment with melatonin and taurine improved these alterations.
Additionally, the histopathological examination demonstrated that caffeine altered the normal structure of liver, hippocampus and cerebral cortex. Concomitant treatment of these rats with melatonin and taurine protected against most of the induced histological alterations and showed nearly normal structures of the hepatic lobules, hippocampus region, and cerebral cortex with a more potent effect in the group treated with 50 mg/kg taurine.
In conclusion, the possible protective effects of melatonin and taurine on caffeine-induced oxidative stress, apoptosis, DNA damage, abnormal cerebral monoamine neurotransmitters, elevated liver enzymes and histopathological effects may be explained based on oxidant-antioxidant system management, regulation of the inflammatory status as well as preventing the apoptosis.