Liliana Rivera-Espinosa

Role of Oxidative Stress in Refractory Epilepsy: Evidence in Patients and Experimental Models

Oxidative stress, a state of imbalance in the production of reactive oxygen species and nitrogen, is induced by a wide variety of factors. This biochemical state is associated with systemic diseases, and diseases affecting the central nervous system. Epilepsy is a chronic neurological disorder with refractoriness to drug therapy at about 30%. Currently, experimental evidence supports the involvement of oxidative stress in seizures, in the process of their generation, and in the mechanisms associated with refractoriness to drug therapy. Hence, the aim of this review is to present information in order to facilitate the handling of this evidence and determine the therapeutic impact of the biochemical status for this pathology.

Overview of Nrf2 as Therapeutic Target in Epilepsy

Oxidative stress is a biochemical state of imbalance in the production of reactive oxygen and nitrogen species and antioxidant defenses. It is involved in the physiopathology of degenerative and chronic neuronal disorders, such as epilepsy. Experimental evidence in humans and animals support the involvement of oxidative stress before and after seizures. In the past few years, research has increasingly focused on the molecular pathways of this process, such as that involving transcription factor nuclear factor E2-related factor 2 (Nrf2), which plays a central role in the regulation of antioxidant response elements (ARE) and modulates cellular redox status. The aim of this review is to present experimental evidence on the role of Nrf2 in this neurological disorder and to further determine the therapeutic impact of Nrf2 in epilepsy.

Modulation of Antioxidant Enzymatic Activities by Certain Antiepileptic Drugs (Valproic Acid, Oxcarbazepine, and Topiramate): Evidence in Humans and Experimental Models

It is estimated that at least 100 million people worldwide will suffer from epilepsy at some point in their lives. This neurological disorder induces brain death due to the excessive liberation of glutamate, which activates the postsynaptic N-methyl-D-aspartic acid (NMDA) receptors, which in turn cause the reuptake of intracellular calcium (excitotoxicity). This excitotoxicity elicits a series of events leading to nitric oxide synthase (NOS) activation and the generation of reactive oxygen species (ROS). Several studies in experimental models and in humans have demonstrated that certain antiepileptic drugs (AEDs) exhibit antioxidant effects by modulating the activity of various enzymes associated with this type of stress. Considering the above-mentioned data, we aimed to compile evidence elucidating how AEDs such as valproic acid (VPA), oxcarbazepine (OXC), and topiramate (TPM) modulate oxidative stress.

Relevance of the Glutathione System in Temporal Lobe Epilepsy: Evidence in Human and Experimental Models

Oxidative stress, which is a state of imbalance in the production of reactive oxygen species and nitrogen, is induced by a wide variety of factors. This biochemical state is associated with diseases that are systemic as well as diseases that affect the central nervous system. Epilepsy is a chronic neurological disorder, and temporal lobe epilepsy represents an estimated 40% of all epilepsy cases. Currently, evidence from human and experimental models supports the involvement of oxidative stress during seizures and in the epileptogenesis process. Hence, the aim of this review was to provide information that facilitates the processing of this evidence and investigate the therapeutic impact of the biochemical status for this specific pathology.

Contributions of Microdialysis to New Alternative Therapeutics for Hepatic Encephalopathy

Hepatic encephalopathy (HE) is a common complication of cirrhosis, of largely reversible impairment of brain function occurring in patients with acute or chronic liver failure or when the liver is bypassed by portosystemic shunts. The mechanisms causing this brain dysfunction are still largely unclear. The need to avoid complications caused by late diagnosis has attracted interest to understand the mechanisms underlying neuronal damage in order to find markers that will allow timely diagnosis and to propose new therapeutic alternatives to improve the care of patients. One of the experimental approaches to study HE is microdialysis; this technique allows evaluation of different chemical substances in several organs through the recollection of samples in specific places by semi-permeable membranes. In this review we will discuss the contributions of microdialysis in the understanding of the physiological alterations in human hepatic encephalopathy and experimental models and the studies to find novel alternative therapies for this disease.

Biochemical and molecular modulation of CCl4-induced peripheral and central damage by Tilia americana var. mexicana extracts

Around the world, species from the genus Tilia are commonly used because of their peripheral and central medicinal effects; they are prepared as teas and used as tranquilizing, anticonvulsant, and analgesic agents. In this study, we provide evidence of the protective effects of organic and aqueous extracts (100 mg/kg, i.p.) obtained from the leaves of Tilia americana var. mexicana on CCl4-induced liver and brain damage in the rat. Protection was observed in the liver and brain (cerebellum, cortex and cerebral hemispheres) by measuring the activity of antioxidant enzymes and levels of malondialdehyde (MDA) using spectrophotometric methods. Biochemical parameters were also assessed in serum samples from the CCl4-treated rats. The T. americana var. mexicana leaf extracts provided significant protection against CCl4-induced peripheral and central damage by increasing the activity of antioxidant enzymes, diminishing lipid peroxidation, and preventing alterations in biochemical serum parameters, such as the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-globulin (γ-GLOB), serum albumin (ALB), total bilirubin (BB), creatinine (CREA) and creatine kinase (CK), relative to the control group. Additionally, we correlated gene expression with antioxidant activity in the experimental groups treated with the organic and aqueous Tilia extracts and observed a non-statistically significant positive correlation. Our results provide evidence of the underlying biomedical properties of T. americana var. mexicana that confer its neuro- and hepatoprotective effects.

Cuantificación sanguínea de metformina y glibenclamida para endocrinología pediátrica

Background: The recent use of antidiabetic drugs such as metformin and glyburide for the treatment and control of childhood obesity, insulin resistance and type II diabetes mellitus in children and adolescents, has encouraged physicians to determine plasma levels of these drugs for the right dose adjustment. Objective: To implement and validate a UPLC-UV method to quantify metformin and glyburide in blood samples. Materials and methods: Only a 0.1 mL-volume blood sample was used. Both drugs are removed by precipitation with methanol. Quantitation was carried out with mobile phase of 4.6 mM potassium phosphate monobasic (KH2PO4) 0.1 M pH = 6.5, sodium dodecyl sulphate (SDS) and acetonitrile (63:7:30), at 0.8 mL/min through a VARIAN Pursuit® C8 150 x 3.9 mm column at 40°C, 236 nm. Results: The method allows the measurement of 20 to 600 nanograms of metformin and from 100 to 2 000 nanograms of glyburide per milliliter of blood. Both drugs are physicochemically stable in blood samples for up to 30 days at 4°C. Conclusion: Our method allows quantification of metformin and gly- buride in paediatric blood samples, to support the clinicians to monitor treatment compliance, bioavailability and pharmacokinetic profiles.

The Use of Microdialysis in the Study of Encephalopathies

Microdialysis is a technique that was devised by Bito et al. (1966) in a study to determine free aminoacids and electrolytes in cerebrospinal fluid and blood plasma in dogs. It consists of recollection of samples in specific places by using semi-permeable membranes, used to evaluate compounds (endogenous neurotransmitters or exogenous such as drugs), in extracellular spaces from different tissues as brain, skin, subcutaneous, tumors, kidney, abdominal and femoral adipose tissue, muscle, lung, middle ear fluid, and other extracellular spaces like blood. Currently, one of the main applications of this methodology in the field of neuroscience is to conduct studies to monitor the release of different substances in brain of conscious and unconscious anesthetized animals. The technique has also been used in surgical procedures as well as in monitoring patients in intensive care unit with traumatic brain injury and subarachnoid hemorrhage. It is employed in neuronal diseases like Epilepsy, Alzheimer, Parkinson, Huntington, Amyotrophic Lateral Sclerosis (ALS) and Encephalopathies.