Some aspects of in vitro studies of neurotoxicity: from choice of biochemical and molecular markers to the confirmation of their informativity

Abstract

The use of laboratory animals in pharmacological and toxicological studies is axiomatic from the point of experimental science and will always be conducted. But these studies are laborious, require additional personnel, the presence of a vivarium, cause the suffering of animals and their death. Therefore, since the late 80's of the last century in the scientific community of Europe and the US actively discusses the issue of toxicological studies in vitro and, in particular, neurotoxicological studies in vitro. But the use of various molecular and biochemical markers of the central nervous system in neurotoxicological studies in vitro, as well as the morphometric parameters of a neuron, can be difficult, because they can be changed by neuroprotective, and not neurotoxic, action of a potential drug. That's why, it is necessary to identify and use molecular or bioche-I. S. Chekman et al. mical markers, that make it possible to clearly judge about only the neurotoxicity of the drugs. We first discovered a correlation of the expression of 70 kDa protein-chaperones with the disruption of the functioning of the glutathione unit of the thiol-disulfide system on the background of injection of the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). Injection of MPTP caused a decrease in the reduced form of glutathione and indirectly led to the deprivation of HSP70 protein expression. The revealed mechanism can be one of the manifestations of the neurotoxic effect of some neuropsychoric drugs. We revealed statistically significant linear dependence of the development of neurological deficit from the functioning of the conjugate system "nitric oxidereduced thiols". The obtained results reveal the importance of the neuron glutathione system as an important target of neuroprotective therapy in ischemic stroke and are the experimental justification for the clinical application of thiol-disulphide system modulators. The coefficient of the ratio of nitrotyrosine to reduced glutathione can be used for the purpose of early laboratory diagnosis of cognitive-mnestic disorders in patients with cerebral pathology. Thus, we identified specific markers for in vitro experiments, that had the greatest potential in providing information on some important mechanisms of neurotoxicity.

Relationship between biochemical parameters and glomerular filtration rate by Cockcroft-Gault, CKD EPI and cystatin C in patients with type 1 diabetes

“…But this practice is often not carried out, which leads to inaccurate interpretation of indicators by a doctor. Failure to comply with this condition is often a situation where the analysis without exaggeration is a technical filing in the map of the disease, without their full understanding and use in treatment [10,11].…”

Some aspects of neuroprotective action of a new derivative of 3-methylxanthine (compound C-3) under conditions of acute disorder of cerebral circulation (ADCC) modeling by ischemic stroke type

“…The concept of neuroprotection to highlights two main areas of stroke therapy. Primary neuroprotection aims to break fast mechanisms of necrotic cell deaththe reactions of calcium-glutamate cascade (antagonists of NMDA and AMPA receptors, and calcium channel blockersremacemid, relutek, nimotop, et al) [4]. Secondary neuroprotection is focused on reduction of severity of long-term consequences of ischemiathe blockade of proinflammatory cytokines, cell adhesion molecules, inhibition of oxidative stress, normalization of neurometabolic processes, inhibition of apoptosis (antioxidants, nootropics, neuropeptides: emoxipine, thiotriazolin, glycine, piracetam, tiocetam, cerebrolysin, cortexin, cerebrocurin, et al) [5].…”