The effect of new derivatives of 3-hydroxypyridine on the development of brain edema in bacterial purulent meningitis in experimental conditions

Abstract

Bacterial purulent meningitis (BPM) is one of the most severe infectious and inflammatory diseases of the nervous system, which is characterized by high mortality and frequent development of residual neurological deficits. Edema and swelling of the brain is the most common cause of death in patients with neuroinfections. Most often, brain edema develops in pneumococcal meningitis (PM), which has the highest mortality rate among all bacterial meningitis. The aim of our work was to study the effect of new derivatives of 3-hydroxypyridine, 2-ethyl-6-methyl-3-hydroxypyridinium 2.6-dichlorophenyl (amino)phenylethanoic acid (EMHDA) and bis(2-ethyl-6-methyl-3-hydroxypyridinium) 2.6-dichlo-rophenyl (amino)phenylethanoic acid (B-EMHDA), on the degree of brain edema in the simulation of BPM in experimental conditions.Material and methods. BPM was modeled by injecting a suspension containing Streptococcus pneumoniae at a concentration of 5 x 109 CFU/ml into the subarachnoid space of the brain. The degree of severity of cerebral edema in rats was assessed by determining the content of total water, free and bound fractions in the brain tissue, as well as the hydration coefficient. The lower the hydration coefficient, the more pronounced the cerebral edema. Determination of the content of water fractions in brain tissue and blood was carried out by the thermogravimetric method.Results and discussion. 24 hours after the induction of meningitis, the free water content increases and the amount of bound water decreases. That testifies to the development of cerebral edema. Hydration coefficient in the group treated with EMHDA at a dose of 50 mg/kg, increased by 11.5 % relative to the control group; in the group receiving EMHDA at a dose of 25 mg/kg, increased by 15.3 % compared to the control group (p<0.05). Hydration coefficient in the group treated with B-EMHDA at a dose of 50 mg/kg, increased by 23 % relative to the control group; in the group receiving B-EMHDA at a dose of 25 mg/kg, increased by 26.9 % compared to the control group; and the group receiving B-EM-HDA at a dose of 12.5 mg/kg was 19.2 % higher relative to the control group (p<0.05).Conclusion. Brain edema is least pronounced when using B-EMHDA at all three studied dosages - 50, 25 and 12.5 mg/kg. Injection of EMHDA at doses of 50 mg/kg and 25 mg/kg also helped to reduce the degree of brain edema when modeling BPM in experimental conditions.

3-Hydroxypyridine and 3-(Hydroxymethyl)pyridine in the Synthesis of Salts of Aryldithiophosphonic Acids on the Basis of Monoterpenyl Alcohols

“…As pharmacological agents for the correction of ischemic brain injury after intracerebral hemorrhage, derivatives of 3-hydroxypyridine such as 3-hydroxy-2-ethyl-6-methylpyridinium, Nacetylaminohexanoate, 4-aminobenzoate, Nacetylaminoacetate, and hydroxybutanedioate were used on rats (7,8). Вacterial purulent meningitis of rats caused by Streptococcus pneumoniae leads to edema of the brain, which is reduced when 2-ethyl-6-methyl-3hydroxypyridinium 2,6-dichlorophenyl (amino)phenylethanoic acid and bis(2-ethyl-6methyl-3-hydroxypyridinium) 2,6-dichlorophenyl (amino)phenylethanoic acid are administered to rats (9). 3-Hydroxy-2-methylpyridine, 3-hydroxy-6methylpyridine and 3-hydroxy-2,6-dimethylpyridine abolish lysozyme fibril formation that is associated with protein-misfolding disorders, including prevalent neurodegenerative diseases (10).…”