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.

Ceftriaxone Attenuated Anxiety-Like Behavior and Enhanced Brain Glutamate Transport in Zebrafish Subjected to Alcohol Withdrawal.

Chronic and/or excessive consumption of alcohol followed by reduced consumption or abstention can result in Alcohol Withdrawal Syndrome. A number of behavioral changes and neurological damage result from ethanol (EtOH) withdrawal. Ceftriaxone (Cef) modulates the activity of excitatory amino acid transporters by increasing their gene expression. Zebrafish are commonly used to study alcohol exposure. The aim of this study was to evaluate the influence of Cef (100 µM) on behavior patterns, glutamate transport activity, and oxidative stress in zebrafish brains subjected to EtOH (0.3% v/v) withdrawal. The exploratory tests using Novel tank showed that EtOH withdrawal promoted a decrease in the time spent and number of entries of in the bottom displaying an anxiety-like behavior. In contrast, treatment with Cef resulted in recovery of exploratory behavioral patterns. Ceftriaxone treatment resulted in increased glutamate uptake in zebrafish subjected to EtOH withdrawal. Furthermore, EtOH withdrawal increased reactive species, as determined using thiobarbituric acid and dichlorodihydrofluorescein assays. Treatment with Cef reversed these effects. Ceftriaxone promoted a significant reduction in brain sulfhydryl content in zebrafish subjected to EtOH withdrawal. Therefore, Cef treatment in conjunction with EtOH withdrawal induced anxiolytic-like effects due to possible neuromodulation of glutamatergic transporters, potentially through mitigation of oxidative stress.

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.