8 research outputs found
Anti-inflammatory and cell proliferative effect of the 1270 nm laser irradiation on the BALB/c Nude mouse model involves activation of the cell antioxidant system
Recently, many interdisciplinary community researchers have focused their efforts on study of the low-level light irradiation effects (photobiomodulation, PBM) as a promising therapeutic technology. Among the priorities, a search of new wavelength ranges of laser radiation to enhance the laser prospects in treatment of autoimmune and cancer diseases commonly accompanied by disorders in the antioxidant system of the body. The laser wavelengths within 1265-1270 nm corresponds to the maximum oxygen absorption band. Therefore, PBM effects on a model organism within this spectrum range are of particular interest for preclinical research. Here, we report comprehensive biomolecular studies of the changes in the BALB/c nude mice skin after an exposure to the continuous laser radiation at the 1270 nm wavelength and energy densities of 0.12 and 1.2 J/cm2. Such regime induces both local and systemic PBM effects, presumably due to the short-term increase in ROS levels, which in turn activate the cell antioxidative system
ΠΠΎΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠ΅ ΡΠΎΠΊΡΠΈΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ΅ ΠΈΠ·ΡΡΠ΅Π½ΠΈΠ΅ Π°Π»ΠΎΡΠ°Π½ΠΈΠ±Π° β Π°Π»Π»ΠΎΡΡΠ΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠ° ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° ΡΠ°ΠΊΡΠΎΡΠ° ΡΠΎΡΡΠ° ΡΠΈΠ±ΡΠΎΠ±Π»Π°ΡΡΠΎΠ² 2 ΡΠΈΠΏΠ°
Background. Inhibition of fibroblast growth factor receptor type 2 (FGFR2) appears to be appropriate in patients with tumors expressing or amplifying FGFR2. The toxicity of allosteric FGFR2 inhibitors has not been previously studied.Purpose. Evaluation of the toxicity of the anticancer drug alofanib (RPT835), allosteric inhibitor of fibroblast growth factor receptor 2 type (FGFR2), in standard experimental in-vivo models in rodents and non-rodents.Material and methods. The general toxic effect of the alofanib was studied in an acute and chronic experiment on outbred animals (rats and rabbits) of both sexes. An experimental study was conducted in accordance with the ethical principles of handling laboratory animals.Results. The assumption that inhibition of FGFR2 provides a low level of toxicity has been proved. It was established that alofanib belongs to the 4 class of low-toxic chemical substances according to the classification of hazard levels of toxic effects of drugs and to the low-risk drugs by the value of the index of the therapeutic action, as well as to the 3 class (low-toxic drugs) according to the class of hazards for clinical application. Alofanib doesnΒ»t cause allergenic and immunotoxic effects as well as doesnΒ»t have pyrogenic properties. Increase of phosphates level (class-specific adverse effect of FGFR2 inhibitors) was statistically significant but less evident. During the study was noticed such an adverse effect as inhibition of spermatogenesis.Conclusion. Alofanib belongs to the classes of low-hazard and low-toxic chemicals and can be studied in a clinical study.ΠΠΊΡΡΠ°Π»ΡΠ½ΠΎΡΡΡ. ΠΠ½Π³ΠΈΠ±ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° ΡΠ°ΠΊΡΠΎΡΠ° ΡΠΎΡΡΠ° ΡΠΈΠ±ΡΠΎΠ±Π»Π°ΡΡΠΎΠ² 2 ΡΠΈΠΏΠ° (Π€Π Π€Π 2) ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»ΡΠ΅ΡΡΡ ΡΠ΅Π»Π΅ΡΠΎΠΎΠ±ΡΠ°Π·Π½ΡΠΌ Ρ Π±ΠΎΠ»ΡΠ½ΡΡ
Ρ ΠΎΠΏΡΡ
ΠΎΠ»ΡΠΌΠΈ, ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡΡΡΡΠΈΠΌΠΈ ΠΈΠ»ΠΈ Π°ΠΌΠΏΠ»ΠΈΡΠΈΡΠΈΡΡΡΡΠΈΠΌΠΈ Π€Π Π€Π 2. Π’ΠΎΠΊΡΠΈΡΠ½ΠΎΡΡΡ Π°Π»Π»ΠΎΡΡΠ΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠΎΠ² Π€Π Π€Π 2 ΡΠ°Π½Π΅Π΅ Π½Π΅ ΠΈΠ·ΡΡΠ°Π»Π°ΡΡ.Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ. ΠΡΠ΅Π½ΠΊΠ° ΡΠΎΠΊΡΠΈΡΠ½ΠΎΡΡΠΈ ΠΏΡΠΎΡΠΈΠ²ΠΎΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΠΎΠ³ΠΎ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ° Π°Π»ΠΎΡΠ°Π½ΠΈΠ± (RPT835), Π°Π»Π»ΠΎΡΡΠ΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠ° ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° ΡΠ°ΠΊΡΠΎΡΠ° ΡΠΎΡΡΠ° ΡΠΈΠ±ΡΠΎΠ±Π»Π°ΡΡΠΎΠ² 2 ΡΠΈΠΏΠ° (Π€Π Π€Π 2), Π² ΡΡΠ°Π½Π΄Π°ΡΡΠ½ΡΡ
ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Π»ΡΠ½ΡΡ
ΠΌΠΎΠ΄Π΅Π»ΡΡ
in vivo Π½Π° Π³ΡΡΠ·ΡΠ½Π°Ρ
ΠΈ Π½Π΅Π³ΡΡΠ·ΡΠ½Π°Ρ
.ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. ΠΠ±ΡΠ΅ΡΠΎΠΊΡΠΈΡΠ΅ΡΠΊΠΎΠ΅ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ° Π±ΡΠ»ΠΎ ΠΈΠ·ΡΡΠ΅Π½ΠΎ Π² ΠΎΡΡΡΠΎΠΌ ΠΈ Ρ
ΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΌ ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ΅ Π½Π° Π±Π΅ΡΠΏΠΎΡΠΎΠ΄Π½ΡΡ
ΠΆΠΈΠ²ΠΎΡΠ½ΡΡ
(ΠΊΡΡΡΠ°Ρ
ΠΈ ΠΊΡΠΎΠ»ΠΈΠΊΠ°Ρ
) ΠΎΠ±ΠΎΠ΅Π³ΠΎ ΠΏΠΎΠ»Π°. ΠΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Π»ΡΠ½ΠΎΠ΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ Π±ΡΠ»ΠΎ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΎ Π² ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²ΠΈΠΈ Ρ ΡΡΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΠΏΡΠΈΠ½ΡΠΈΠΏΠ°ΠΌΠΈ ΠΎΠ±ΡΠ°ΡΠ΅Π½ΠΈΡ Ρ Π»Π°Π±ΠΎΡΠ°ΡΠΎΡΠ½ΡΠΌΠΈ ΠΆΠΈΠ²ΠΎΡΠ½ΡΠΌΠΈ.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΡΠ΅Π΄ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ΠΈΠ΅ ΠΎ ΡΠΎΠΌ, ΡΡΠΎ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠΎΠ»ΡΠΊΠΎ ΠΎΠ΄Π½ΠΎΠ³ΠΎ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° Π€Π Π€Π 2 ΠΎΠ±Π΅ΡΠΏΠ΅ΡΠΈΡ Π½ΠΈΠ·ΠΊΠΈΠΉ ΡΡΠΎΠ²Π΅Π½Ρ ΡΠΎΠΊΡΠΈΡΠ½ΠΎΡΡΠΈ, ΠΏΠΎΠ΄ΡΠ²Π΅ΡΠ΄ΠΈΠ»ΠΎΡΡ. Π£ΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΡΠΎ Π°Π»ΠΎΡΠ°Π½ΠΈΠ± ΠΎΡΠ½ΠΎΡΠΈΡΡΡ ΠΊ 4 ΠΊΠ»Π°ΡΡΡ ΠΌΠ°Π»ΠΎΡΠΎΠΊΡΠΈΡΠ½ΡΡ
Ρ
ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΡ
Π²Π΅ΡΠ΅ΡΡΠ² ΠΏΠΎ ΠΊΠ»Π°ΡΡΠΈΡΠΈΠΊΠ°ΡΠΈΠΈ ΡΡΠ΅ΠΏΠ΅Π½ΠΈ ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΠΈ ΡΠΎΠΊΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΡ
ΡΡΠ΅Π΄ΡΡΠ² ΠΈ ΠΊ ΠΌΠ°Π»ΠΎΠΎΠΏΠ°ΡΠ½ΡΠΌ Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΠΌ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ°ΠΌ ΠΏΠΎ Π²Π΅Π»ΠΈΡΠΈΠ½Π΅ ΠΈΠ½Π΄Π΅ΠΊΡΠ° ΡΠΈΡΠΎΡΡ ΡΠ΅ΡΠ°ΠΏΠ΅Π²ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΊ 3 ΠΊΠ»Π°ΡΡΡ (ΠΌΠ°Π»ΠΎΡΠΎΠΊΡΠΈΡΠ½ΡΠΉ Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΠΉ ΠΏΡΠ΅ΠΏΠ°ΡΠ°Ρ) Π² ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²ΠΈΠΈ Ρ ΠΊΠ»Π°ΡΡΠΎΠΌ ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΠΈ Π΄Π»Ρ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΡ. ΠΠ»ΠΎΡΠ°Π½ΠΈΠ± Π½Π΅ ΠΎΠΊΠ°Π·ΡΠ²Π°Π΅Ρ Π°Π»Π»Π΅ΡΠ³ΠΈΠ·ΠΈΡΡΡΡΠ΅Π³ΠΎ ΠΈ ΠΈΠΌΠΌΡΠ½ΠΎΡΠΎΠΊΡΠΈΡΠ½ΠΎΠ³ΠΎ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ ΠΈ Π½Π΅ ΠΎΠ±Π»Π°Π΄Π°Π΅Ρ ΠΏΠΈΡΠΎΠ³Π΅Π½Π½ΡΠΌΠΈ ΡΠ²ΠΎΠΉΡΡΠ²Π°ΠΌΠΈ. Π£Π²Π΅Π»ΠΈΡΠ΅Π½ΠΈΠ΅ ΡΡΠΎΠ²Π½Ρ ΡΠΎΡΡΠ°ΡΠΎΠ² (ΠΊΠ»Π°ΡΡ-ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π½Π΅ΠΆΠ΅Π»Π°ΡΠ΅Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠ²Π»Π΅Π½ΠΈΡ Π€Π Π€Π ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠΎΠ²) Π±ΡΠ»ΠΎ ΡΡΠ°ΡΠΈΡΡΠΈΡΠ΅ΡΠΊΠΈ Π΄ΠΎΡΡΠΎΠ²Π΅ΡΠ½ΡΠΌ, Π½ΠΎ ΠΌΠ°Π»ΠΎΠ²ΡΡΠ°ΠΆΠ΅Π½Π½ΡΠΌ. Π ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΈ ΠΎΡΠΌΠ΅ΡΠ΅Π½ ΡΠ°ΠΊΠΎΠΉ ΠΏΠΎΠ±ΠΎΡΠ½ΡΠΉ ΡΡΡΠ΅ΠΊΡ ΠΊΠ°ΠΊ ΡΠ³Π½Π΅ΡΠ΅Π½ΠΈΠ΅ ΡΠΏΠ΅ΡΠΌΠ°ΡΠΎΠ³Π΅Π½Π΅Π·Π°.ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΠ»ΠΎΡΠ°Π½ΠΈΠ± ΠΎΡΠ½ΠΎΡΠΈΡΡΡ ΠΊ ΠΊΠ»Π°ΡΡΠ°ΠΌ ΠΌΠ°Π»ΠΎΠΎΠΏΠ°ΡΠ½ΡΠΌ ΠΈ ΠΌΠ°Π»ΠΎΡΠΎΠΊΡΠΈΡΠ½ΡΡ
Ρ
ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΡ
Π²Π΅ΡΠ΅ΡΡΠ² ΠΈ ΠΌΠΎΠΆΠ΅Ρ ΠΈΠ·ΡΡΠ°ΡΡΡΡ Π² ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΌ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΈ
The role of light desynchronosis in the development of stress-induced aging
The long-term change of the light mode for three months β light desynchronosis, disturbs the rhythm of the signals received from the external pacemaker. As a result of the study, it was found that a long-term change in the light mode and a violation of the rhythmicity of signals received from an external pacemaker contributes to the activation of ROS formation as triggers for bioenergetic processes in the cell. At the same time, changing the light mode disrupts the balance of oxygen in the cell and this is a provoking factor for the stress of the antioxidant cell system. The resulting tissue hypoxia in chronic light desynchronosis disrupts the bioenergetic potential of the cell, contributing to the development of pathophysiological processes and the death of neurons. Therefore, a violation of the balance of the pro-oxidant and anti-oxidant systems leads to destructive processes in the brain. A significant change in the concentration of the neurotrohic markers indicates destructive processes in the brain tissues. Summarizing the above, we conclude that light desynchronosis is directly involved in the ROS-dependent stress-induced aging of brain cells and in that way, to the progression of processes that lead to aging of the body