Ascorbigen — Rifabutin Toxicity Modifier

2020 ◽  
Vol 65 (9-10) ◽  
pp. 13-20
Author(s):  
E. R. Pereverzeva ◽  
M. I. Treshchalin ◽  
I. D. Treshchalin
Keyword(s):  
Body Weight ◽  
Body Weight Gain ◽  
Hematological Parameters ◽  
Combined Treatment ◽  
Gastrointestinal Toxicity ◽  
Histological Evaluation ◽  
Hematological Toxicity ◽  
Blood Biochemical ◽  
Combined Use ◽  
Male Wistar Rats

Relevance. Indications for rifabutin use are constantly expanding. It is used in the treatment of extremely complex nosological forms of infectious diseases. However, side effects of the medication, such as gastrointestinal toxicity and myelosuppression, in many cases do not allow the completion of treatment and weaken the patient-s adherence to therapy. This determines the need to find means to reduce the toxic properties of rifabutin.Objective. The aim of the study was to investigate the possibility of correction of gastrointestinal and hematological toxicity of rifabutin with ascorbigen.Material and Methods. The study was performed in male Wistar rats. The drugs were administered per os at therapeutic doses (50 mg/kg daily for 15 days). Ascorbigen was administered 30 minutes before rifabutin. Body weight dynamics, hematological parameters, blood biochemical parameters, electrocardiography, and urinalysis were performed for all animals during the study. Five animals in each group were euthanized on the 1st and 30th days after the end of the treatment course. The internal organs were subjected to histological evaluation.Results. It has been shown that combined treatment with rifabutin and ascorbigen leads to a weakening of the damaging effect of the antibiotic on the mucous membrane of the gastrointestinal tract and accelerates the processes of restoration of its structure. Clinically, this is expressed in the normalization of body weight gain of animals. The combined use of rifabutin with ascorbigen reduces the depth of cytopenia. The number of leukocytes in the peripheral blood of the rats was restored faster. There were no signs of atrophy of spleen-s lymphoid tissue. The administration of ascorbigen before rifabutin has a protective effect on the tissues of the kidneys and testes.Conclusion. Oral administration of ascorbigen 30 minutes before rifabutin significantly reduces the gastrointestinal toxicity and hematotoxicity of rifabutin and prevents the development of spermatogenesis disorders. This allows us to recommend it for combined use in order to improve tolerance to anti-TB treatment.

scholarly journals Experimental evaluation of toxic properties of LCTA-2034 by the oral routeof administration

2018 ◽  
Vol 17 (3) ◽  
pp. 81-88 ◽  
Author(s):  
M. I. Treschalin ◽  
I. D. Treschalin ◽  
V. A. Golibrodo ◽  
A. E. Shchekotikhin ◽  
E. R. Pereverzeva
Keyword(s):  
Body Weight ◽  
Therapeutic Dose ◽  
Clinical Laboratory ◽  
Hematological Parameters ◽  
Relative Weight ◽  
Oral Route ◽  
Post Treatment ◽  
Histological Evaluation ◽  
High Dose ◽  
Blood Biochemical

Introduction.New antitumor multitarget drug LCTA-2034, obtained in Gause Institute of New Antibiotics, has demonstrated high activity against prognostically significant transplantable mice tumors by the oral application.Objective.To investigate the toxicological properties of LCTA-2034 by the oral route of administration on rats.Materials and methods.Toxicological study of LCTA-2034 was performed on 30 male Wistar rats. Drug substance dissolved in potable water. 2 % solution was administrated per os at the 1 and 5 therapeutic dose (15 × 20 mg/kg or 15 × 100 mg/kg with 24-h interval). During the study dynamics of body weight, hematological parameters, blood biochemical parameters, electrocardiography and urinalysis were performed for all animals. Five animals in each group were sacrificed 1 and 30 days post treatment. The internal organs were subjected to histological evaluation.Results.The results of the study demonstrate that the treatment with low dose of LCTA-2034 does not produce any changes in majority of examined clinical-laboratory parameters with the exception of urinalysis revealed hematuria on day 1 post treatment. Microscopic pathology observation showed structure abnormalities of varying severity in liver, kidneys, heart, stomach, jejunum, ileum, spleen and thymus. Administration of high dose of LCTA-2034 caused mortality of 2 rats in group. The rest of the rats were observed a body weight lag, decrease of total leukocyte and erythrocyte count, hemoglobin and hematocrit level, relative weight of the thymus. Erythrocytes and nitrates were found in urine both on day 1 and on day 30 post treatment. In groups treated with high dose of the drug in addition to the listed above organs damage of the structure of lymph nodes, pancreas, ileum and brain was detected. Conclusion. Revealed toxic properties of LCTA-2034 depended on dose. Multiple administration of 1 therapeutic dose of the drug produces transient toxic effects completely reversible within 30 days. 

Practical Application of Microcapsulation for Toxicity Studies Using Bromodichloromethane as a Model Compound

1989 ◽  
Vol 8 (6) ◽  
pp. 1177-1187
Author(s):  
Y. Aida ◽  
M. Ando ◽  
K. Takada ◽  
J Momma ◽  
H. Yoshimoto ◽  
...  
Keyword(s):  
Body Weight ◽  
Olive Oil ◽  
Body Weight Gain ◽  
Male Rats ◽  
Toxicity Tests ◽  
Bile Duct Proliferation ◽  
Volatile Chemicals ◽  
Feeding Study ◽  
Toxicity Studies ◽  
Male Wistar Rats

Gelatin-starch syrup (food grade) microcapsulation was applied for toxicology studies of bromodichloromethane (BDCM). BDCM concentrations were stable for 120 days in the microcapsules and for 9 months when incorporated in the powder diet. BDCM concentration in the blood following the administration of microcapsules in olive oil suspension was retained at higher levels than when BDCM was administered as olive oil solution. Subsequently, the microcapsules were mixed in powder diet and were given at concentrations of microcapsulated BDCM of 0, 0.024, 0.072, and 0.215% to groups of 7 male Wistar rats for 1 month. For comparison, BDCM dissolved in olive oil was administered by gavage to groups of 7 male rats for 1 month at dosage levels adjusted to those in the feeding study (0, 20, 60, and 180 mg/kg body weight). Suppression of body weight gain was seen in the high-dosage groups in both the feeding and the gavage studies and was more severe in the former. Similar histopathologic lesions in the liver were shown in both studies, including vacuolization, swelling, and single necrosis of liver cells. Hepatic cord irregularity and bile duct proliferation were observed in the feeding study but not the gavage study. Serum biochemical changes, such as decreases in glucose, triglyceride, and cholinesterase levels, which reflected the histopathologic findings in the liver, were also observed in both studies. Accordingly, the microcapsulation process was proved to pose no qualitative toxic effects on toxicity of BDCM in short-term toxicity studies. It is concluded that the application of microcapsulation is useful for toxicity tests of volatile chemicals when incorporated into food.

scholarly journals TOXICOLOGICAL PROPERTIES OF BIOMODIFIED ENZYME DRUG - L-ASPARAGINASE WAS79

2015 ◽  
Vol 14 (4) ◽  
pp. 53-58
Author(s):  
E. R. Pereverzeva ◽  
I. D. Treschalin ◽  
E. V. Voznyakovskaya ◽  
M. I. Treschalin ◽  
T. B. Pereverzeva ◽  
...  
Keyword(s):  
Body Weight ◽  
Liver Toxicity ◽  
Clinical Chemistry ◽  
Hematological Parameters ◽  
Internal Organs ◽  
Blood Biochemical ◽  
Pancreatic Toxicity ◽  
Urinary Parameters ◽  
Microscopic Pathology ◽  
Dose Dependent

Toxicological study of L-asparaginase Was79, obtained by modification of native enzyme Wolinella succinogenes in Research Institute of Genetics and Selection, was performed in male and female inbred rats. L-asparaginase was injected intraperitoneally at the 1 and 10 therapeutic dose (15x1200 IU/kg or 15x12000 IU/kg with 24-h interval). Dynamics of body weight, hematological parameters, blood biochemical parameters, electrocardiography and urinalysis were performed for all animals. Five animals in each group were sacrificed 1 and 15 days post treatment. At necropsy, the organs were inspected macroscopically. The mass coefficients of heart, kidneys, liver, spleen and thymus were calculated. The pathomorphological evaluation was performed for internal organs. The results of the study demonstrate that the treatment with L-asparaginase Was79 did not produce any changes in body weight, hematology, blood biochemical or urinary parameters. Hematological, renal, gastrointestinal, and pancreatic toxicity of L-asparaginase have been documented only by microscopic pathology observation. Liver toxicity, revealed in the histopathological findings, was supported by the results of clinical chemistry. Marked elevation of ALT and alkaline phosphatase in serum was found in both treated groups. Most of these abnormalities were reversible and dose-dependent.

scholarly journals Η μελέτη της αντιοξειδωτικής και αντιφλεγμονώδους δράσης μορίων (U-74389G και σιλδεναφίλης) σε πειραματικό πρότυπο χημικής αιμορραγικής κολίτιδας σε επίμυες

2014 ◽  
Author(s):  
Γεώργιος-Αντώνιος Μαργώνης
Keyword(s):  
Body Weight ◽  
Combined Treatment ◽  
Damage Index ◽  
Mucosal Damage ◽  
Group 4 ◽  
Tnf Α ◽  
Male Wistar Rats ◽  
Experimental Rat Model ◽  
Anti Inflammatory ◽  
Group 5

BACKGROUND: Crohn disease is still incurable. Compounds with anti-inflammatory and/or antioxidativeeffects are tested in various preclinical models of the disease. Our aim was to investigate theeffects of sildenafil and lazaroid U-74389G in an experimental rat model oftrinitrobenzenesulfonic acid-induced colitis.MATERIALS AND METHODS:Trinitrobenzenesulfonic acid was instilled into the colon of all male Wistar rats except for therats belonging to the first group. For 6 days, the animals in group 3 were administered dailysildenafil orally, the rats in group 4 were administered daily U-74389G intravenously, and therats in group 5 were coadministered daily sildenafil orally and intravenous U-74389G. Therats in groups 1 and 2 were not administered any treatment. During the study, the weightswere recorded as a marker of clinical condition. The colon damage was evaluated usingmacroscopic colon mucosal damage index (CMDI), microscopic (Geboes score), andbiochemical methods (tissue tumor necrosis factor [TNF]-αΝandΝmalondialdehydeΝ[εϊχ]ΨέRESULTS:Sildenafil reduced TNF-αΝtissueΝlevelsΝandΝincreasedΝbodyΝweightέΝU-74389G reduced TNF-α,Νthe macroscopic index of mucosal damage score (CMDI) and increased body weight. Thecombined treatment with sildenafil and U-74389G reduced tissue levels of both TNF-αΝandΝMDA, lowered CMDI and microscopic Geboes score, and increased body weight. CONCLUSIONS:U-74389G demonstrated a significant anti-inflammatory activity related to its ability to reducecolonic TNF-α,ΝωεϊIΝscore, and improve weight change. We confirmed that sildenafil hasanti-inflammatory capacity by reducing colonic TNF-αΝandΝbyΝimprovingΝbodyΝweightέΝόinally,Νthe combined treatment showed superior effects by reducing colonic TNF-α,ΝcolonicΝεϊχ,ΝCMDI score, Geboes score, and by improving weight.

scholarly journals Effects of Purified Jatropha curcas Seed Oil-Based Diet on Growth Performance and Hematological Parameters of Albino Rats

2015 ◽  
Vol 4 (1) ◽  
Author(s):  
A Maiyaki-Musa
Keyword(s):  
Body Weight ◽  
Growth Performance ◽  
Jatropha Curcas ◽  
Seed Oil ◽  
Body Weight Gain ◽  
Hematological Parameters ◽  
Control Diet ◽  
Test Group ◽  
Albino Rats ◽  
Test Diet

The effect of inclusion of Jatropha curcas seed oil, as a source of oil in the feed of animal, on growth performance, hematological parameters and histology was investigated. Feed intake, average body weight gain and mortality were also monitored. Milled Jatropha curcas seeds were subjected to oil extraction using batch method. Hematological parameters were determined using standard operating procedures. Twenty weanling albino rats with mean weights ranging from 41.57± 7.90 g, were divided into two groups. The first group was placed on soybean oil-based (control) diet (4% oil) while the second group was placed on Jatropha curcas seed oil-based diet (4% oil), for four weeks. There was a significant higher difference (P<0.05) in the growth performance of rats fed the control diet when compared with the test group. The animals placed on the control diet showed significantly higher (P<0.05) body weight when compared with the test diet during the last week of experimentation and this might be due to the low digestibility of the Jatropha curcas seed oil-based diet. The result also shows a higher percentage mortality in the group fed the test diet when compared with those fed the control diet. Hematological parameters did not differ significantly (P>0.05) in both the control and test diets respectively but a significantly higher difference in neutrophils of those fed the control diet when compared with those fed test diet. This may signify that continuous ingestion of Jatropha curcas seed oil may reduce the body’s immunity against infections. The histological assessment of liver, kidney, heart and small intestine revealed no visible lesion. Overall, the result showed that Jatropha curcas seed oil has the potential of been a source of oil in animal diet if complete detoxification can be achieved.

scholarly journals A Combination of Apple Vinegar Drink with Bacillus coagulans Ameliorates High Fat Diet-Induced Body Weight Gain, Insulin Resistance and Hepatic Steatosis

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2504
Author(s):  
Raquel Urtasun ◽  
Joana Díaz-Gómez ◽  
Miriam Araña ◽  
María José Pajares ◽  
María Oneca ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Bacillus Coagulans ◽  
Normal Diet ◽  
High Fat ◽  
Blood Biochemical ◽  
Traditional Remedy

Obesity is a worldwide epidemic characterized by excessive fat accumulation, associated with multiple comorbidities and complications. Emerging evidence points to gut microbiome as a driving force in the pathogenesis of obesity. Vinegar intake, a traditional remedy source of exogenous acetate, has been shown to improve glycemic control and to have anti-obesity effects. New functional foods may be developed by supplementing traditional food with probiotics. B. coagulans is a suitable choice because of its resistance to high temperatures. To analyze the possible synergic effect of Vinegar and B. coagulans against the metabolic alterations induced by a high fat diet (HFD), we fed twelve-week-old C57BL/6 mice with HFD for 5 weeks after 2 weeks of acclimation on a normal diet. Then, food intake, body weight, blood biochemical parameters, histology and liver inflammatory markers were analyzed. Although vinegar drink, either alone or supplemented with B. coagulans, reduced food intake, attenuated body weight gain and enhanced glucose tolerance, only the supplemented drink improved the lipid serum profile and prevented hepatic HFD-induced overexpression of CD36, IL-1β, IL-6, LXR and SREBP, thus reducing lipid deposition in the liver. The beneficial properties of the B. coagulans-supplemented vinegar appear to be mediated by a reduction in insulin and leptin circulating levels.

Evaluation of the effectiveness of ironcontaining drugs in the complex therapy of antenatal hypotrophy of piglets

2021 ◽  
Vol 1 (6) ◽  
pp. 13-17
Author(s):  
R. V. Rogov ◽  
◽  
Zh. Yu. Muradyan ◽  
I. G. Ryazanov ◽  
◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Clinical Study ◽  
Body Weight Gain ◽  
Hematological Parameters ◽  
Live Weight ◽  
The Body ◽  
Treatment Regimens ◽  
Complex Therapy ◽  
Experimental Group

In the conditions of the pig breeding complex, the effectiveness of two treatment regimens for antenatal hypotrophy of piglets was studied. Two groups of piglets were formed, where the ironcontaining drug «Ursoferran – 200» was used in complex therapy in the 1st experimental group, and «Ferropen-200»in the 2nd experimental group. In a clinical study, hypotrophic piglets showed characteristic symptoms of the disease. In the experiment, the live weight of piglets was measured at the time of farrowing and on the 3rd, 7th, 14th and 21st days of life. The hematological parameters were studied. The most pronounced therapeutic effect was observed in the 1st experimental group, where the body weight gain was higher by 8,3% than in the 2nd experimental group.

scholarly journals Blood Biochemical and Immunological Responses to Garlic Oil Administration in Growing Rabbits Diet

2017 ◽  
Vol 10 (1) ◽  
pp. 217
Author(s):  
M. R. EL-Gogary ◽  
A. M. Mansour ◽  
E. A. El-Said
Keyword(s):  
Body Weight ◽  
Antioxidant Status ◽  
Plasma Lipids ◽  
Body Weight Gain ◽  
Blood Parameters ◽  
Coliform Bacteria ◽  
Feed Conversion ◽  
Immunological Responses ◽  
Garlic Oil ◽  
Blood Biochemical

The effect of dietary supplementation garlic oil on performance and blood parameters of New Zealand White rabbits has been studied. The garlic oil was added at graded levels of 0.0, 0.25, 0.5 and 0.75 g/kg for T1 (control), T2, T3 and T4, respectively. A total of thirty six male rabbits, 7 weeks of age and with an initial weigh of 950 g were used. There were four treatments, each with three replicates (n = 3) in randomly divided design. The parameters investigated were growth performance, carcass yield, glucose, plasma lipids profile, immunoglobulin’s G (IgG, IgA and IgM), antioxidant status and testosterone hormone. The results showed that feeding diet supplemented with garlic oil had insignificant effect on body weight, body weight gain, feed intake, feed conversion ratio, triglycerides, cholesterol, LDL and HDL. Rabbits fed the 0.5 g/kg garlic oil diet had significantly increased IgG level, hence improved immune responses and Testosterone hormone of rabbits. The colony forming units of coliform bacteria showed a significantly lower number compared with control. The present results indicate that supplemented of garlic oil at 0.5 g/kg of diet has a positive effect on HDL, immunoglobulin’s G, antioxidant status and testosterone hormone in addition to its antibacterial effect.

scholarly journals Effects of indigenous medicinal plant Tulsi (Ocimum sanctum) leaves extract as a growth promoter in broiler

2015 ◽  
Vol 2 (1) ◽  
pp. 97-102
Author(s):  
Firoj Alom ◽  
Mahbub Mostofa ◽  
M Nurul Alam ◽  
M Golam Sorwar ◽  
Jashim Uddin ◽  
...  
Keyword(s):  
Body Weight ◽  
Treatment Group ◽  
Body Weight Gain ◽  
Hematological Parameters ◽  
Vaccination Schedule ◽  
Ocimum Sanctum ◽  
Control Group ◽  
Broiler Chicks ◽  
Growth Promoter ◽  
Live Body Weight

The study was conducted to determine the efficacy of Tulsi (Ocimum sanctum ) leaves extract as a growth promoter in broiler. Thirty (30) day-old broiler chicks were purchased from Kazi hatchery and after seven days of acclimatization in the poultry shed of Pharmacology department randomly divided into two groups I0 and I1. No vaccination schedule was practiced and no antibiotics were added in rations. Group was supplemented with Tulsi (Ocimum sanctum) leaves extract @ 2ml/litre in drinking water. Weekly observations were recorded for live body weight gain upto 5th weeks and blood test was performed at 17th and 35th day’s age of broiler to observe the hematological changes between control (Group) and treatment (Group) group. The treatment group (Group A) recorded statistically non- significant for live body weight at 1st and 2nd weeks than that of control group (Group B) but found statistically significant at 3rd (p<0.01), 4th (P<0.05) and 5th (P<0.01) weeks of age and the Hematological parameters (TEC, PCV, Hb and ESR) showed statistically significant (p<0.01) difference as compared to control group.Res. Agric., Livest. Fish.2(1): 97-102, April 2015

Knocking down the diencephalic thyrotropin-releasing hormone precursor gene normalizes obesity-induced hypertension in the rat

2007 ◽  
Vol 292 (5) ◽  
pp. E1388-E1394 ◽  
Author(s):  
María S. Landa ◽  
Silvia I. García ◽  
Mariano L. Schuman ◽  
Adriana Burgueño ◽  
Azucena L. Alvarez ◽  
...  
Keyword(s):  
Body Weight ◽  
Body Weight Gain ◽  
Strong Association ◽  
Green Fluorescence Protein ◽  
Antisense Oligodeoxynucleotide ◽  
Arterial Blood ◽  
Induced Hypertension ◽  
Male Wistar Rats ◽  
Antisense Sequence ◽  
Systolic Arterial Blood Pressure

We recently showed that diencephalic TRH may mediate the central leptin-induced pressor effect. Here, to study the role of TRH in obesity-induced hypertension (OIH), we used a model of OIH produced by a high-fat diet (HFD, 45 days) in male Wistar rats. After 4 wk, body weight and systolic arterial blood pressure (SABP) increased in HFD animals. Plasma leptin was correlated with peritoneal adipose tissue. Then, we treated OIH animals with an antisense oligodeoxynucleotide and small interfering (si)RNA against the prepro-TRH. Antisense significantly decreased diencephalic TRH content and SABP at 24 and 48 h posttreatment. Similar effects were observed with siRNA against prepro-TRH but for up to 4 wk. Conversely, vehicle, an inverted antisense sequence and siRNA against green fluorescence protein, produced no changes. SABP decrease seems to be owing to an inhibition of the obesity-enhanced sympathetic outflow but not to an alteration in thyroid status. Using a simple OIH model we demonstrated, for the first time, that central TRH participates in the hypertension induced by body weight gain probably through its well-known action on sympathetic activity. Thus the TRH-leptin interaction may contribute to the strong association between hypertension and obesity.

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