Gallic acid modulates purine metabolism and oxidative stress induced by ethanol exposure in zebrafish brain.

Gallic acid (GA) is a secondary metabolite found in plants. It has the ability to cross the blood-brain barrier and, through scavenging properties, has a protective effect in a brain insult model. Alcohol metabolism generates reactive oxygen species (ROS); thus, alcohol abuse has a deleterious effect on the brain. The zebrafish is a vertebrate often used for screening toxic substances and in acute ethanol exposure models. The aim of this study was to evaluate whether GA pretreatment (24 h) prevents the changes induced by acute ethanol exposure (1 h) in the purinergic signaling pathway in the zebrafish brain via degradation of extracellular nucleotides and oxidative stress. The nucleotide cascade promoted by the nucleoside triphosphate diphosphohydrolase (NTPDase) and 5'-nucleotidase was assessed by quantifying nucleotide metabolism. The effect of GA alone at 5 and 10 mg L-1 did not change the nucleotide levels. Pretreatment with 10 mg L-1 GA prevented an ethanol-induced increase in ATP and ADP levels. No significant difference was found between the AMP levels of the two pretreatment groups. Pretreatment with 10 mg L-1 GA prevented ethanol-enhanced lipid peroxidation and dichlorodihydrofluorescein (DCFH) levels. The higher GA concentration was also shown to positively modulate against ethanol-induced effects on superoxide dismutase (SOD), but not on catalase (CAT). This study demonstrated that GA prevents the inhibitory effect of ethanol on NTPDase activity and oxidative stress parameters, thus consequently modulating nucleotide levels that may contribute to the possible protective effects induced by alcohol and purinergic signaling.

Melatonin Pretreatment Protects Against Status epilepticus, Glutamate Transport, and Oxidative Stress Induced by Kainic Acid in Zebrafish.

Status epilepticus (SE) develops from abnormal electrical discharges, resulting in neuronal damage. Current treatments include antiepileptic drugs. However, the most common drugs used to treat seizures may sometimes be ineffective and have many side effects. Melatonin is an endogenous physiological hormone that is considered an alternative treatment for neurological disorders because of its free radical scavenging property. Thus, this study aimed to determine the effects of melatonin pretreatment on SE by inducing glutamatergic hyperstimulation in zebrafish. Seizures were induced in zebrafish using kainic acid (KA), a glutamate analog, and the seizure intensity was recorded for 60 min. Melatonin treatment for 7 days showed a decrease in seizure intensity (28%), latency to reach score 5 (14 min), and duration of SE (29%). In addition, melatonin treatment attenuated glutamate transporter levels, which significantly decreased in the zebrafish brain after 12 h of KA-induced seizures. Melatonin treatment reduced the increase in oxidative stress by reactive oxygen species formation through thiobarbituric acid reactive substances and 2',7'-dichiorofluorescin, induced by KA-seizure. An imbalance of antioxidant enzyme activities such as superoxide dismutase and catalase was influenced by melatonin and KA-induced seizures. Our study indicates that melatonin promotes a neuroprotective response against the epileptic profile in zebrafish. These effects could be related to the modulation of glutamatergic neurotransmission, recovery of glutamate uptake, and oxidative stress parameters in the zebrafish brain.

Gallic Acid Reverses Neurochemical Changes Induced by Prolonged Ethanol Exposure in the Zebrafish Brain.

Gallic acid (GA) is a polyphenolic compound that has attracted significant interest due to its antioxidant action through free radical elimination and metal chelation. Ethanol is a highly soluble psychoactive substance, and its toxicity is associated with oxidative stress. In this context, the purpose of the present study was to investigate the effect of GA on neurochemical changes in zebrafish brains exposed to ethanol. GA was first analyzed in isolation by treating the animals at concentrations of 5, 10, and 20 mg/L for 24 h and 48 h. The results revealed that the group exposed to 20 mg/L over a 24/48 h period exhibited increases in thiobarbituric acid reactive substance (TBA-RS) levels and 2',7'-dichlorofluorescein (DCFH) oxidation, demonstrating a pro-oxidant profile. Moreover, decrease in acetylcholinesterase (AChE) enzyme activity was observed. To investigate the effects of GA after ethanol exposure, the animals were divided into four groups: control; those exposed to 0.5% ethanol for 7 days; those exposed to 0.5% ethanol for 7 days and treated with GA at 5 and 10 mg/L on day 8. Treatment with GA at 5 and 10 mg/L reversed impairment of choline acetyltransferase activity and the damage to TBA-RS levels, DCFH oxidation, and superoxide dismutase activity induced by ethanol. Results of the present study suggest that GA treatment (20 mg/L) appeared to disrupt oxidative parameters in the zebrafish brain. GA treatment at 5 and 10 mg/L reversed alterations to the cholinergic system induced by prolonged exposure to ethanol in the zebrafish brain, probably through an antioxidant mechanism.