ABSTRACT
The free radical and cytokine statuses of the cornea during its thermal burn and the possibility of its correction by lactoferrin have been studied in Soviet Chinchilla rabbits. The development of a corneal thermal burn was accompanied by the development of oxidative stress (increased levels of TBA-reactive substances and carbonyl derivatives of proteins, decreased activity of SOD and GPx enzymes) and a pronounced inflammatory reaction with increased levels of TNF-1α, IL-10, TGF-1ß. The use of lactoferrin had a pronounced therapeutic effect, which was manifested by accelerated healing, prevention of the development of complications (corneal perforations), a decrease in the severity of oxidative stress, an increase in the concentrations of TNF-1α (in the early stages), IL-10 (in the later stages), TGF-1ß (throughout the experiment). At the same time, by the end of regeneration more severe corneal opacification was recognized compared to the control group. This may be associated with an increased level of anti-inflammatory cytokines, especially TGF-1ß.
Subject(s)
Cornea , Lactoferrin , Oxidative Stress , Animals , Lactoferrin/pharmacology , Rabbits , Cornea/metabolism , Cornea/drug effects , Oxidative Stress/drug effects , Cytokines/metabolism , Eye Burns/metabolism , Eye Burns/drug therapy , Eye Burns/chemically induced , Eye Burns/pathology , Male , Free Radicals/metabolism , Corneal Injuries/metabolism , Corneal Injuries/drug therapy , Corneal Injuries/pathology , Disease Models, AnimalABSTRACT
In experiments on HepG2 cells, we studied the effect of the original domestic neurotropic drugs omberacetam, fabomotizole, and ethylmethylhydroxypyridine succinate (EMHPS) (1-500 µM) on the activity and content of organic anion transporting polypeptides OATP1B1 and OATP1B3. It was shown that omberacetam (500 µM) increased the content of OATP1B1 and OATP1B3, fabomotizole did not affect the level of both transporters, and EMHPS (500 µM) increased the content of OATP1B1 compared to the control and did not affect the level of OATP1B3. The tested substances also reduced the OATP1B1/OATP1B3 ratio, as evidenced by a decrease in the penetration of atorvastatin, a substrate of the transporters, into HepG2 cells in the presence of omberacetam (100-500 µM), fabomotizole (500 µM), and EMHPS (10-500 µM). Evaluation of clinical significance of the obtained results, according to the FDA approach based on the calculation of the Cmax/IC50 ratio, showed that the effect of the tested substances on OATP1B1/OATP1B3 is clinically insignificant.
