scholarly journals Mechanism of antisurdant action of triazin-indole derivative at experimental acoustic trauma

2021 ◽  
Vol 16 (1) ◽  
pp. 13-19
Author(s):  
Vladimir Pastushenkov ◽  
◽  
Maxim Kuznecov ◽  
Vladimir Dvorjanchikov ◽  
Alexander Pastushenkov ◽  
...  

In our research performed using model of acoustic trauma at experimental animals (female of hybrids F1 of CBA and C57BL/6 lines) influence of triazin-indole at expression level of hypoxia induced factor (HIF) in Corti’s organ was studied at its therapy application. As a reference drug cytoflavin was used. Investigated drug in the form of 1 % solution was introduced into animals parenterally in dosage 5, 7, 10 mg/kg with 2 hr intervals after acoustic impact. Injection of cytoflavin as reference drag was performed in 1.7 ml/kg dosage. Level of HIF expression in the drug of Corti’s organ was estimated using immunohistochemical method. It was found out that triazin-indole derivative increases HIF expression in Corti’s cells and in neurons of spiral ganglion at acoustical traumatic impact depending on drug dosage increase. Maximal HIF expression in Corti’s cells and in ganglions were noted at therapeutic dose of the drug 10 mg/kg. In control group and in the group with application citoflavin in dose 1.7 ml/kg minimal HIF expression was observed. According to obtained results of performed investigation the authors concluded that antisurdant property of triazin-indole derivative is realized through the influence on HIF metabolism (probably, by blockage of prolyl hydroxylase) and enables to consider it as a target molecular during the drug application.

2021 ◽  
Vol 11 (3) ◽  
pp. 365-372
Author(s):  
Vladimir L. Pastushenkov ◽  
Leonid G. Buynov ◽  
Maksim S. Kuznetsov ◽  
Vladimir V. Dvorianchikov ◽  
Lev A. Glaznikov ◽  
...  

The effect of triazino-indole derivative (Trisan) on hypoxia-inducible factor (HIF) expression level in the organ of Corti, when administering it for therapeutic and preventive purposes, was investigated using an acoustic trauma model in experimental animals (female F1 hybrids of CBA and C57BL/6 lines). Cytoflavin was used as a comparator product. Study product Trisan (1% solution) was injected intravenously, intramuscularly and intraperitoneally, in the dose of 5, 7 and 10 mg/kg 2 h after the acoustic trauma for therapeutic purposes and in the dose of 5, 7 and 10 mg/kg for 3 days before the acoustic trauma for preventive purposes. IHC methods were used to investigate the organ of Corti. Trisan was observed to increase HIF expression in hair cells and neurons of the spiral ganglion in case of acoustic trauma. Depending on the dose, the increased HIF-1 expression in hair cells and spiral ganglion occurred both after therapeutic and preventive use of Trisan. Maximum HIF expression in hair cells and ganglion was noted at the therapeutic and preventive drug dose of 10 mg/kg. Following experimental results, we conclude that the otoprotective effect of triazino-indole derivative is realized via its effect on HIF metabolism, which makes it a target molecule for the drug.


2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Przemysław Baranowski ◽  
Bożena Karolewicz ◽  
Maciej Gajda ◽  
Janusz Pluta

This paper describes hitherto developed drug forms for topical ocular administration, that is, eye drops, ointments,in situgels, inserts, multicompartment drug delivery systems, and ophthalmic drug forms with bioadhesive properties. Heretofore, many studies have demonstrated that new and more complex ophthalmic drug forms exhibit advantage over traditional ones and are able to increase the bioavailability of the active substance by, among others, reducing the susceptibility of drug forms to defense mechanisms of the human eye, extending contact time of drug with the cornea, increasing the penetration through the complex anatomical structure of the eye, and providing controlled release of drugs into the eye tissues, which allows reducing the drug application frequency. The rest of the paper describes recommendedin vitroandin vivostudies to be performed for various ophthalmic drugs forms in order to assess whether the form is acceptable from the perspective of desired properties and patient’s compliance.


2017 ◽  
Vol 7 (2) ◽  
Author(s):  
Belde Culhaoglu ◽  
Selim S. Erbek ◽  
Seyra Erbek ◽  
Evren Hizal

Acoustic trauma is a common reason for hearing loss. Different agents are used to prevent the harmful effect of acoustic trauma on hearing. The aim of this study was to evaluate the potential preventive effect of <em>Nigella sativa</em> (black cumin) oil in acoustic trauma. Our experimental study was conducted with 20 Sprague Downey female rats (mean age, 12 months; mean weight 250 g). All of the procedures were held under general anesthesia. Following otoscopic examinations, baseline-hearing thresholds were obtained using auditory brainstem responses (ABR). To create acoustic trauma, the rats were then exposed to white band noise of 4 kHz with an intensity level of 107 dB in a soundproof testing room. On Day 1 following acoustic trauma, hearing threshold measurements were repeated. The rats were divided into two groups as the study group (n: 10) and the controls (n: 10). 2 mL/kg/day of <em>Nigella sativa</em> oil was given to the rats in the study group orally. On Day 4 following acoustic trauma, ABR measurements were repeated again. There was no difference between the baseline hearing thresholds of the rats before acoustic trauma (P&gt;0.005). After the acoustic trauma, hearing thresholds were increased and there was no significant statistically difference between the hearing thresholds of the study and control groups (P=0.979). At the 4<sup>th</sup> day following acoustic trauma, hearing thresholds of the rats in control group were found to be higher than those in the study group (P=0.03). Our results suggest that <em>Nigella sativa</em> oil has a protective effect against acoustic trauma in early period. This finding should be supported with additional experimental and clinical studies, especially to determine the optimal dose, duration and frequency of potential <em>Nigella sativa</em> oil therapy.


2021 ◽  
Vol 74 (2) ◽  
pp. 213-219
Author(s):  
Varvara A. Berezhna ◽  
Tetiana V. Mamontova ◽  
Antonina M. Gromova

The aim: To elucidate the possible involvement of M1 and M2 macrophages in the placentas of women, whose pregnancies were complicated by fetal growth restriction (FGR) and resulted in term births after 37 weeks of gestation and preterm births up to 37 weeks of gestation. Materials and methods: CD68+ and CD163+ macrophages were studied by immunohistochemical method, placental morphology in the placentas of 16 women whose pregnancies were complicated by FGR and resulted in term births at a gestational age after 37 weeks (1-st group, n = 7) or resulted in preterm births at a gestational age up to 37 weeks (2-nd group, n = 9). The control group consisted of 10 placentas of women with physiological pregnancies and births. Results: Women 2-nd group showed significantly low weight of the placenta, a short gestation period at the time of delivery, and a prolonged labor period than women of the control group (p <0.001; p <0.001; p <0.05, respectively). The level of CD68+ and CD163+ macrophages in the placentas of women 2-nd group was significantly higher than in woman 1-st group (p <0.001, p <0.001, respectively). A significant correlation was found between the expression level of CD68+ monocytes in the intervillous space and the weight of a newborn (r = – 0.765; p = 0.016) in women 2-nd group. Conclusions: These studies suggest that in the placentas of women whose pregnancies were complicated by FGR and resulted in preterm births, the increased activation of CD68+ macrophages of the pro-inflammatory pool may be associated with disorders of the vascular and stromal component of the villous chorion with the development of involutive and dystrophic changes. In general, this fact probably determines the progress of chronic placental insufficiency and aggravates the development of fetal growth restriction.


2019 ◽  
Vol 9 (1-s) ◽  
pp. 113-120
Author(s):  
Soumya S Dash ◽  
Smaranika Pattnaik

The aim of this study was to evaluate the antifungal efficacy of Kocuria marina (BMKo1) derived Lactic acid against Epidermophyton floccosum (MTCC-613) infections induced on male Swiss Albino mice model (Mus musculus).  For this purpose, the isolated strain was subjected to ‘flask fermentation’ and the Lactic acid produced as fermentation product, was quantified and analysed. Prior to preclinical test, healthy mice models of approximately 8 weeks old and 25-30 gm (weight) were subjected to intra-dermal administration for a period of 15 days to test for toxicity. Mortality, clinical signs, body weight changes were continually monitored. Then the mouse models were inoculated with 100 µl/ml (V/V) of E. floccosum (MTCC-613) spore suspensions following ‘Excision model’. After induction of the infection, the symptomatic mice groups were subjected to topical application of Kocuria lactic acid cream based formulation at a concentration of 1µl/ml (V/V). The naked eye observations were made on the infected lesions till the absolute deduction of infection of excised skin surfaces. The degrees of deduction of infection were converted into scores and the percentages (%) of deduction of infection were calculated and the average value was derived. There were inclusion of positive control (Fluconazole) and negative control (group with infection induced excision, but without any drug application) mice groups for the sake of comparison. Further, with absolute deduction of infection score observed in mice group, applied with Kocuria derived Lactic acid was akin to Fluconazole activity. However, the infection induced mice group was found to be with substantial increase of degree of infection. This study have curtain raised about the anti Epidermophyton infection activity of a cream based  Cell free Lactic acid derived from a non pathogenic strain of Kocuria marina on mouse models. Keywords: Kocuria marina, Epidermophyton floccosum, Lactic acid


2016 ◽  
Vol 6 (1) ◽  
pp. 40-48
Author(s):  
K. Jakubowska ◽  
A. Pryczynicz ◽  
V. Dymicka-Piekarska ◽  
D. Cepowicz ◽  
D. Jagodzińska ◽  
...  

Purpose: Growth differentiation factor-15 (GDF- 15) protein belongs to a transforming growth factor-β family which determines the growth and differentiation of cells. In cancers, GDF-15 influences on the proliferation, differentiation, viability, migration and invasiveness of cancer cells. The aim of our study was to evaluate the expression of GDF-15 in the tissue and its levels in sera of patients with colorectal cancer. Materials and methods: The level of GDF-15 in the sera of 55 patients diagnosed with colorectal cancer was determined using the ELISA method whereas expression of this protein was performed by immunohistochemical method. Results: The mean value of GDF-15 levels in the sera of patients with colorectal cancer was significantly higher than in healthy control group (p<0.001). The expression of GDF-15 in the tissue was weak, moderate and strong in 23.6%, 15.7% and 60.7% cases, respectively. Statistical analysis showed that the expression of GDF-15 correlated with patients’ age (p<0.005) and non-mucinous type of cancer (p<0.001). The high GDF-15 levels in the serum was associated with tumor size (p<0.01) and distant metastases (p<0.05). Conclusions: According to our results, we postulate that the level of GDF-15 in serum can be use to assess the metastatic behavior of colorectal cancer


2019 ◽  
Author(s):  
Agnès Job ◽  
Anne Kavounoudias ◽  
Chloé Jaroszynski ◽  
Assia Jaillard ◽  
Chantal Delon-Martin

ABSTRACTTinnitus mechanisms remain poorly understood. Our previous functional MRI (fMRI) studies demonstrated an abnormal hyperactivity in the right parietal operculum 3 (OP3) in acoustic trauma tinnitus and during provoked phantom sound perceptions without hearing loss, which lead us to propose a new model of tinnitus. This new model is not directly linked with hearing loss and primary auditory cortex abnormalities, but with a proprioceptive disturbance related to middle-ear muscles. In the present study, a seed-based resting-state functional MRI method was used to explore the potential abnormal connectivity of this opercular region between an acoustic trauma tinnitus group presenting slight to mild tinnitus and a control group. Primary auditory cortex seeds were also explored because they were thought to be directly involved in tinnitus in most current models. In such a model, hearing loss and tinnitus handicap were confounding factors and were therefore regressed in our analysis. Between-groups comparisons showed a significant specific connectivity between the right OP3 seeds and the potential human homologue of the premotor ear-eye field (H-PEEF) bilaterally and the inferior parietal lobule (IPL) in the tinnitus group. Our findings suggest the existence of a simultaneous premotor ear-eye disturbance in tinnitus that could lift the veil on unexplained subclinical abnormalities in oculomotor tests found in tinnitus patients with normal vestibular responses. The present work confirms the involvement of the OP3 subregion in acoustic trauma tinnitus and provides some new clues to explain its putative mechanisms.


2021 ◽  
Vol 5 (6) ◽  
pp. 16-19
Author(s):  
Chunpeng Wang ◽  
Xiaohui Liu ◽  
Shiwen Guo

Objective: The purpose of this study is to explore the role of sphingosine kinase 2 (SphK2) in the treatment of glioma, which is the most common primary tumor in the central nervous system. Methods: A total of 82 patients were included in this study, with 27 cases in the control group and 55 cases in the glioma group; the expressions of SphK2 and gp130 in the two groups were compared by immunohistochemical method, and the correlation between the two factors was analyzed. Results: Both SphK2 and gp130 were upregulated in the glioma group, and the two factors were significantly correlated. Conclusion: The high expression of SphK2 may play an important role in the occurrence, development, and diagnosis of glioma.


2019 ◽  
pp. 82-87
Author(s):  
B. V. Pristupa ◽  
I. O. Shyshkin ◽  
Ya. V. Rozhkovsky ◽  
V. O. Gelmboldt

In the last decade, high cariesprophylactic efficacy of ammonium hexafluorosilicates, including salts with substituted biologically active ammonium cations, has been demonstrated. Among the promising anti-caries agents are recently synthesized 2-, 3-, 4-carboxymethylpyridinium hexafluorosilicates, for whose cations anti-inflammatory activity is expected. The aim of the work is to assess the presence of anti-inflammatory activity in the series of 2-, 3-, 4-carboxymethylpyridinium hexafluorosilicates in the experiment. 2-, 3-, 4-Carboxymethylpyridinium hexafluorosilicates (I–III, respectively) were synthesized according to the previously proposed technique, carrageenan is a commercial preparation, reference drug is a indomethacin. Experiments on the anti-inflammatory activity of hexafluorosilicates were performed on 77 white Wistar male rats weighing 174–190 g using the carrageenan model of inflammation. The inflammatory reaction was reproduced by subplantary administration of 0.1 ml of a 0.2% solution of carrageenan, the studied compounds were administered orally in doses 1/10, 1/20, 1/50 from LD50 for the compound III. It was established that after administration of carrageenan, animals of the control group showed marked paw edema, which gradually increased and was maximal after 24 hours of observation. According to the data obtained, the indices for compounds I-III practically do not differ from those of the control group. This indicates that, despite the results of the PASS forecast and the presence of acetic acid residue, an anti-inflammatory pharmacofor, in compounds I-III, the compounds under study do not have an anti-inflammatory effect in the carrageenan model. 2-, 3-, 4-Carboxymethylpyridinium hexafluorosilicates do not show the expected anti-inflammatory activity in the carrageenan model of inflammation.


Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1993
Author(s):  
Nada M. Mostafa ◽  
Ahmed M. Mostafa ◽  
Mohamed L. Ashour ◽  
Sameh S. Elhady

Oxidative stress is usually associated with many neurodegenerative diseases. In this study, the gas chromatography–mass spectrometry (GC–MS) analysis of cold-pressed oil (CPO) from black pepper (Piper nigrum) fruits was performed and its neuroprotective effects were evaluated for the first time. The analysis of CPO revealed the presence of the lignan sesamin (39.78%), the alkaloid piperine (33.79%), the monoterpene hydrocarbons 3-carene (9.53%) and limonene (6.23%), and the sesquiterpene β-caryophyllene (10.67%). Black pepper hydrodistilled oil (HDO) was also comparatively analyzed by GC–MS to show the impact of oil isolation by two different methodologies on their components and class of compounds identified. HDO analysis revealed 35 compounds (99.64% of the total peak areas) mainly composed of monoterpene hydrocarbons (77.28%), such as limonene (26.50%), sabinene (21.36%), and β-pinene (15.53%), and sesquiterpene hydrocarbons (20.59%) represented mainly by β-caryophyllene (19.12%). Due to the low yield obtained for HDO (0.01% v/w), only CPO was chosen for the evaluation of its neuroprotective potential. Alzheimer-type dementia was induced in rats by scopolamine intraperitoneal injection (1.5 mg/kg/day) for seven days. CPO was administered orally (100 mg/kg) for a week before scopolamine administration and then concomitantly for another week. Donepezil (1 mg/kg, orally) was used as a reference drug. CPO administration significantly improved the rat behaviors as evaluated by the Morris water maze test, evident from prolongation in time spent in the platform quadrant (262.9%, compared to scopolamine) and increasing in the crossing time by 18.18% compared to the control group. The rat behavior tested by passive avoidance, showed prolongation in the step-through latency compared to control. Moreover, CPO significantly (p < 0.05) ameliorated the activities of antioxidant enzymes such as catalase, superoxide dismutase (SOD) and reduced malondialdehyde (MDA) equivalents by 22.48%, 45.41%, and 86.61%, respectively, compared to scopolamine. Furthermore, CPO administration decreased scopolamine-induced elevated acetylcholinesterase levels in rats’ hippocampi by 51.30%. These results were supported by histopathological and in silico molecular docking studies. Black pepper oil may be a potential antioxidant and neuroprotective supplement.


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