scholarly journals Changes of intestinal microbiota and ivabradine biotransformation in rats after alcohol introduction

2017 ◽  
Vol 6 (3) ◽  
pp. 47-51
Author(s):  
Boris Evgenyevich Tolkachev ◽  
Evgeny Igorevich Morkovin ◽  
Liliya Petrovna Knyshova ◽  
Anatoly Trofimovich Yakovlev ◽  
Andrey Valeryevich Strygin

The role of intestinal microbiota in progress of many pathological processes is discussed in recent publications. It was shown that the continuous intestinal dysbiosis, including the increased bacterial growth syndrome, affects the digestion and the biotransformation of xenobiotics. Intestinal microbiota provokes metabolic failures leading to severe diseases acting via several mechanisms. Alcohol is found to be a common dysbiotic factor and toxic agent affecting the systems of biotransformation. This study was to estimate the associations between the intestinal microbiota and the biotransformation of ivabradine, CYP3A4 substrate, in rats during the chronic alcohol intake. The study used 30 male Wistar rats divided into two groups - control and experimental, administrated 15% ethanol as a sole water supply during 40 days to model the chronic alcohol intake. The decrease of bifido- and lactobacterium spp. found in experimental group correlated with excretion and metabolic ratio of ivabradine metabolite and ivabradine in urine. These findings demonstrate the participation of intestinal microbiota in the metabolism of ivabradine after oral introduction.

2021 ◽  
Vol 10 (10) ◽  
pp. 2072
Author(s):  
Phoebe Lin ◽  
Scott M. McClintic ◽  
Urooba Nadeem ◽  
Dimitra Skondra

Blindness from age-related macular degeneration (AMD) is an escalating problem, yet AMD pathogenesis is incompletely understood and treatments are limited. The intestinal microbiota is highly influential in ocular and extraocular diseases with inflammatory components, such as AMD. This article reviews data supporting the role of the intestinal microbiota in AMD pathogenesis. Multiple groups have found an intestinal dysbiosis in advanced AMD. There is growing evidence that environmental factors associated with AMD progression potentially work through the intestinal microbiota. A high-fat diet in apo-E-/- mice exacerbated wet and dry AMD features, presumably through changes in the intestinal microbiome, though other independent mechanisms related to lipid metabolism are also likely at play. AREDS supplementation reversed some adverse intestinal microbial changes in AMD patients. Part of the mechanism of intestinal microbial effects on retinal disease progression is via microbiota-induced microglial activation. The microbiota are at the intersection of genetics and AMD. Higher genetic risk was associated with lower intestinal bacterial diversity in AMD. Microbiota-induced metabolite production and gene expression occur in pathways important in AMD pathogenesis. These studies suggest a crucial link between the intestinal microbiota and AMD pathogenesis, thus providing a novel potential therapeutic target. Thus, the need for large longitudinal studies in patients and germ-free or gnotobiotic animal models has never been more pressing.


2017 ◽  
Vol 10 (4) ◽  
pp. 269-276
Author(s):  
B S Sukovatykh ◽  
A Y Grigoryan ◽  
A I Bezhin ◽  
T A Pankrusheva ◽  
Yu Yu Blinkov ◽  
...  

Relevance. Purulent complications occur in 35-45% of patients with surgical diseases, lethality rate from these conditions achieves 25%. The purpose of the study. To investigate the wound process while treating the purulent wounds with immobilized forms of miramistin and benzalkonium chloride in gel of sodium salt of carboxymetylcellulose. Materials and methods. There were analysed results of experimental study of the wound process on 108 male Wistar rats. Experimental animals were divided into 3 groups, each group included 36 rats. In a comparison group ‘Levomekol’ ointment was used for treatment. In the first experimental group treatment was done by the ointment with the following composition: 0,01% solution of miramistin — 100 g, metronidazol –1,0 g, sodium salt of carboxymetylcellulose — 4,0 g, while in the second experimental group ointment composition included benzalkonium chloride 0,02 g, metronidazol — 1,0 g, sodium salt of carboxymetylcellulose — 4,0 g, purified water — up to 100,0 g. The wound process was evaluated by planimetric, microbiological and histological methods of investigation. Results and its discussion. The reduction of wound area in the first experimental group was higher than in a comparison group on the 3rd day of the experiment by 9,7%, on the 5th day — by 7,6%, on the 10th and 15th days — by 10,5%, while in the second experimental group the change was 37,2%, 27,3%, 13,8% and 6,9% respectively. In the first experimental group microbial contamination of the wound was less than in a comparison group by 5,8х106, on the 5th day — by 3,1х105, on the 10th day — by 6,1х104, while in the second experimental group on the 3rd day there were no differences, on the 5th day — by 6,3х105, on the 10th day — 1,1х104. Histological investigations of the wound biopsies on the 10th day of experiment showed that in a comparison group the bottom of the wound was covered by granulation tissue without signs of epithelization, there was full coverage of the wound with a newly formed epithelium in experimental groups. Conclusions. The use of prolonged quaternary ammonium antiseptics in treatment of purulent wounds is pathogenetically justified and efficient.


2020 ◽  
Vol 21 (13) ◽  
pp. 4815 ◽  
Author(s):  
Ekaterina P. Mochalova ◽  
Svetlana P. Belova ◽  
Tatiana Y. Kostrominova ◽  
Boris S. Shenkman ◽  
Tatiana L. Nemirovskaya

Unloading leads to skeletal muscle atrophy via the upregulation of MuRF-1 and MAFbx E3-ligases expression. Reportedly, histone deacetylases (HDACs) 4 and 5 may regulate the expression of MuRF1 and MAFbx. To examine the HDAC-dependent mechanisms involved in the control of E3-ubiquitin ligases expression at the early stages of muscle unloading we used HDACs 4 and 5 inhibitor LMK-235 and HDAC 4 inhibitor Tasqinimod (Tq). Male Wistar rats were divided into four groups (eight rats per group): nontreated control (C), three days of unloading/hindlimb suspension (HS) and three days HS with HDACs inhibitor LMK-235 (HSLMK) or Tq (HSTq). Treatment with LMK-235 diminished unloading-induced of MAFbx, myogenin (MYOG), ubiquitin and calpain-1 mRNA expression (p < 0.05). Tq administration had no effect on the expression of E3-ligases. The mRNA expression of MuRF1 and MAFbx was significantly increased in both HS and HSTq groups (1.5 and 4.0 folds, respectively; p < 0.05) when compared with the C group. It is concluded that during three days of muscle unloading: (1) the HDACs 4 and 5 participate in the regulation of MAFbx expression as well as the expression of MYOG, ubiquitin and calpain-1; (2) the inhibition of HDAC 4 has no effect on MAFbx expression. Therefore, HDAC 5 is perhaps more important for the regulation of MAFbx expression than HDAC 4.


2020 ◽  
Vol Volume 13 ◽  
pp. 4543-4560
Author(s):  
Toyin Dorcas Alabi ◽  
Charon de Villiers ◽  
Stefan S. du Plessis ◽  
Thomas K. Monsees ◽  
Nicole L. Brooks ◽  
...  

2016 ◽  
Vol 36 (7) ◽  
pp. 734-743 ◽  
Author(s):  
GE Adeleke ◽  
OA Adaramoye

N-nitrosodimethylamine (NDMA) is a toxicant found in foods and drinking water. Several synthetic agents used in alleviation of NDMA toxicity have been associated with serious side effects. Therefore, a safe and less toxic agent is desirable. In this study, betulinic acid (BA), a triterpenoid antioxidant, is proposed as a better and alternative agent to modulate NDMA-induced toxicity. Twenty-four Wistar rats were assigned into four groups of six rats each and treated with normal saline (control), BA (25 mg/kg), NDMA (5 mg/kg) and (BA + NDMA). BA was given by oral gavage for 14 consecutive days, while NDMA was administered intraperitoneally on days 7 and 12. Results showed that administration of NDMA significantly ( p < 0.05) elevated the activities of serum alanine aminotransferase (ALT), aspartate aminotransferase and gamma-glutamyl transferase by 51%, 48% and 81%, respectively. Also, NDMA intoxication significantly ( p < 0.05) increased the levels of serum urea and creatinine by 64% and 82%, respectively, and decreased urinary creatinine by 67%. In addition, administration of NDMA significantly ( p < 0.05) increased the levels of hepatic and renal DNA fragmentation by 44% and 61%, respectively, relative to control. The number of micronucleated polychromatic erythrocytes (mnPCEs) in NDMA-treated rats (11.1 ± 2.6 mnPCE/1000PCE) was significantly higher than control (4.3 ± 1.1 mnPCE/1000 PCE). Immunohistochemistry revealed strong expressions of Bcl-2 and nuclear p53 in NDMA-intoxicated rats. Interestingly, pretreatment with BA significantly ( p < 0.05) ameliorated NDMA-induced changes in serum biochemical indices, mnPCEs, DNA fragmentation and expressions of Bcl-2 and p53 proteins. These findings suggest that BA protects against NDMA-induced toxicity via anti-oxidative and anti-apoptotic activities.


2007 ◽  
Vol 21 (8) ◽  
pp. 843-850 ◽  
Author(s):  
A.M. Myint ◽  
S. O'Mahony ◽  
M. Kubera ◽  
Y.K. Kim ◽  
C. Kenny ◽  
...  

2016 ◽  
Vol 244 ◽  
pp. 187-194 ◽  
Author(s):  
Nachimuthu Maithilikarpagaselvi ◽  
Magadi Gopalakrishna Sridhar ◽  
Rathinam Palamalai Swaminathan ◽  
Bobby Zachariah

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