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. 

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 A 90-Day Oral Toxicity of Hydroethanolic Root Extract of Carissa spinarum in Wistar Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Komlan M. Dossou-Yovo ◽  
Aboudoulatif Diallo ◽  
Povi Lawson-Evi ◽  
Yendubé T. Kantati ◽  
Tchin Darré ◽  
...  
Keyword(s):  
Body Weight ◽  
Biochemical Parameters ◽  
Wistar Rats ◽  
Hematological Parameters ◽  
Relative Weight ◽  
Control Group ◽  
Root Extract ◽  
Weight Changes ◽  
Oral Toxicity ◽  
Significant Difference

Background. Herbal medication is a worldwide and ancient practice, mostly in developing countries, where a large part of the population is involved in this practice. Hence, studies must be conducted to evaluate their safety and efficiency to avoid or prevent toxicological risks due to their usage. In Togo, Carissa spinarum is a medicinal plant belonging to Apocynaceae family, used as an aphrodisiac or to heal some ailments including malaria, sickle cell anemia, hypertension, pain, and asthma. Notwithstanding its several ethnomedicinal benefits, just a few toxicological data associated with its chronic use are available. Objective. Therefore, this study aims to assess the toxicity of an ethanolic root extract of Carissa spinarum in Wistar rats. Methods. The 90-day oral toxicity process following OECD TG 408 guidelines is used. Male Wistar rats received Carissa spinarum root hydroethanolic extract at 500 and 1000 mg/kg for 90 days by oral gavage. Body weight changes, hematological and blood biochemical parameters, organ weight changes, malondialdehyde as a lipoperoxidation marker expressed according to tissue proteins, and histopathology of vital organs were assessed. Results. No signs of toxicity or mortality were observed during the 90 days experiment. Hematological parameters have not shown any treatment-related abnormalities. According to biochemical parameters, an increase in the chloride ion level was observed at 1000 mg/kg p < 0.01 . There was no significant difference between the treated groups and the control group concerning the malondialdehyde concentration, body weight, and organ relative weight. No changes in necropsy and histopathology of vital organs associated with extract treatment were observed. Conclusion. The results indicated that an ethanolic root extract of Carissa spinarum does not cause adverse effects, which can lead to Wistar rats’ death after 90-day oral administration at 500 and 1000 mg.

Acute and sub-chronic toxicity of the aqueous extract of Ficus vogelii (Miq.) Miq. stem bark in rats

2021 ◽  
Vol 10 (2) ◽  
pp. 89-97
Author(s):  
EL Lappa ◽  
◽  
C Bogning Zangueu ◽  
EL Nguemfo ◽  
JJ Kojom Wanche ◽  
...  
Keyword(s):  
Body Weight ◽  
Aqueous Extract ◽  
Chronic Toxicity ◽  
Hematological Parameters ◽  
Lethal Dose ◽  
Relative Weight ◽  
Stem Bark ◽  
The Body ◽  
Female Rats ◽  
Male Rats

Ficus vogelii is a medicinal plant mainly found in tropical Africa and reported to treat inflammatory complaints. This study aims to evaluate the acute and sub-chronic toxicity of the aqueous extract of Ficus vogelii stem bark in wistar rats. For acute study, aqueous extract at a single dose of 5000 mg/kg body weight was administered to female rats and observed for 14 days. In the sub-chronic study, the extract was administered daily to both sex rats at the doses of 100, 200, 400, and 600 mg/kg body weight for 28 consecutive days. Body weight was measured weekly, while hematological, biochemical, and histopathological parameters were analyzed after euthanize. Aqueous extract of Ficus vogelii at all tested doses didn’t produced any mortality or significant change on the body weight and relative weight of rats on acute and sub-chronic studies. The lethal dose 50 was estimated greater than 5000 mg/kg (DL50˃5000 mg/kg). Hematological parameters were recorded non-significant in all treated rats. Aqueous extract at 600 mg/kg significantly changed transaminases and alkaline phosphatase activities, these changes were reversible in satellites. The concentrations of bilirubin was increased at 200 and 600 mg/kg in male rats, at 100, 400 mg/kg in female rats. The levels of lipids markers didn’t changed, except the significant decrease of LDL-cholesterol. Histological examination didn’t showed any change in the architecture of the liver and kidney of rats treated compared to control. Thus aqueous extract of Ficus vogelii stem bark didn’t produced adverse effects in rats after oral acute and sub-chronic treatment.

scholarly journals Thirteen-Week Oral Toxicity Study of HVC1 in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Kyungjin Lee ◽  
Ho-Young Choi
Keyword(s):  
Hematological Parameters ◽  
Clinical Signs ◽  
Ethanol Extract ◽  
New Drugs ◽  
Control Group ◽  
High Dose ◽  
Sprague Dawley ◽  
Weight Changes ◽  
Oral Toxicity ◽  
Blood Biochemical

Studies on the safety of herbal medicine are essential for the development of new drugs. The aim of this study was to evaluate the no-observed-adverse-effect-level (NOAEL) of HVC1 (Gamisamhwangsasim-tang, a 30% ethanol extract of a mixture of Pruni Cortex, Scutellariae Radix, Coptidis Rhizoma, and Rhei Rhizoma) and identify its target organs after oral administration to Sprague-Dawley (SD) rats repeatedly for 13 weeks. Three test groups were treated with HVC1 at a dose of either 500 (low-dose), 1,000 (middle-dose), or 2,000 (high-dose) mg/kg/day. Another group received high-dose HVC1 and was observed for 4 weeks following treatment to examine recovery from the effects of the extract. All treatment groups were compared to a vehicle control group. During the study, mortality, clinical signs, body weight changes, food consumption, abnormal lesions in the eye, urinary parameters, hematological parameters, blood coagulation time, blood biochemical parameters, changes in organ weight, gross findings, and histopathological changes were examined. No systemic toxicity related to HVC1 was observed in any group, and it was concluded that the NOAEL of HVC1 was 2,000 mg/kg/day. No target organ was identified.

In vivo hepatotoxicity of chemically modified nanocellulose in rats

2019 ◽  
Vol 39 (2) ◽  
pp. 212-223 ◽  
Author(s):  
CA Otuechere ◽  
A Adewuyi ◽  
OL Adebayo ◽  
IA Ebigwei
Keyword(s):  
Body Weight ◽  
Relative Weight ◽  
High Dose ◽  
Hydroxyl Groups ◽  
Oral Toxicity ◽  
Tissue Samples ◽  
Liver Histopathology ◽  
Biological Functionality ◽  
Oxide Synthase

Chemical modification of cellulose is currently attracting attention as researchers attempt to take advantage of the abundance of hydroxyl groups on its surface to introduce extra biological functionality. However, the possible deleterious effect of exposure to functionalized nanocellulose (CSN) remains a concern. Therefore, this study aims to explore the potential mechanisms of hepatotoxicity of CSN modified with oxalate ester (NCD) in rats. A 7-day repeated oral toxicity study of NCD at the doses of 50 and 100 mg kg−1 body weight was conducted, and plasma and liver tissue samples were assayed using biochemical analysis, liver histopathology, and protein expression. NCD, at both doses, did not significantly ( p > 0.05) alter the relative weight of liver, alkaline phosphatase activity, and lipid peroxidation levels of the animals. However, NCD at the dose of 100 mg kg−1 body weight significantly elevated aspartate aminotransferase, alanine aminotransferase, and myeloperoxidase activities. NCD also enhanced the immunohistochemical expression of inducible nitric oxide synthase and Bcl-2-associated X protein in the liver of rats. Histological observations revealed necrosis and severe cellular infiltration at the high-dose treatment. Our study provides an experimental basis for the safe application of NCDs.

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 Hepatotoxic and Nephrotoxic Effect of Ethanol Leaf Extract of Scoparia Dulcis (Linn) in Wistar Rats

2021 ◽  
Vol 2 (4) ◽  
pp. 20-27
Author(s):  
Olubodun A. Adebiyi ◽  
Danladi A. Ameh ◽  
Elewechi Onyike ◽  
Dorcas B. James
Keyword(s):  
Body Weight ◽  
Wistar Rats ◽  
Leaf Extract ◽  
Hematological Parameters ◽  
Relative Weight ◽  
Animal Group ◽  
Scoparia Dulcis ◽  
Significant Difference ◽  
Liver And Kidney ◽  
G Ratio

Scoparia dulcis (Linn) is a widespread herbal medicine; it bears an enormous number of pharmacological activities. The present study was undertaken to find out the chronic toxicity profile of oral administration of Scoparia dulcis ethanol leaf extract (SDELE) on the liver and the kidney of wistar rats. The animals were grouped into four and administered varying doses of SDELE (100 mg/kg, 200 mg/kg, 400 mg/kg body weight and 0.2 ml distilled water respectively) for a period of fourteen weeks (100 days). The acute toxicity, body weight, relative organ weight, hematological parameters, biochemical markers for liver and kidney damage were monitored and histopathology of the liver and kidney of the rat were carried out. The LD50 of SDELE was found to be 1131 mg/kg body weight. There was a significant (p<0.05) reduction in weight of the rat administered 400 mg/kg and 200 mg/kg when compared with the control though there was no significant difference (p>0.05) in the relative weight of the organs. There was also a significant increase (p<0.05) in the lymphocytes, serum level of aspartate amino transferase (ASP), alanine amino transferase (ALT), alkali phosphatase (ALP), total protein, A/G ratio, creatinine, urea, uric acid, total cholesterol, triacylglycerol, low density lipoprotein cholesterol and potassium ions while there was a significant decrease in HDL-cholesterol and sodium ions in the animal group administered 400 mg/kg body weight of the extract. Histopathology of the liver and kidney revealed haemorrhage and vascular congestion at 200 mg/kg doses and renal damage at 400 mg/kg body weight doses respectively. However, there was no significant difference (p>0.05) in any of the parameters studied in the group administered 100 mg/kg body weight dose when compared with the controlled group. Ethanol leaf extracts of Scoparia dulcis showed hepatotoxic and nephrotoxic tendencies and should be used with caution especially when employed in the treatment of chronic diseases

scholarly journals Evaluation of Acute and Subacute Toxicities of Psidium guajava Methanolic Bark Extract: A Botanical with In Vitro Antiproliferative Potential

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Hermione T. Manekeng ◽  
Armelle T. Mbaveng ◽  
Samuel A. Ntyam Mendo ◽  
Armel-Joseph D. Agokeng ◽  
Victor Kuete
Keyword(s):  
Body Weight ◽  
Lethal Dose ◽  
Relative Weight ◽  
Psidium Guajava ◽  
Toxicity Study ◽  
Female Rats ◽  
Bark Extract ◽  
Control Group ◽  
High Dose ◽  
Subacute Toxicity

The methanol crude extract of the bark of Psidium guajava (guava) previously displayed interesting cytotoxic effects on a panel of human cancer cell lines. In the present work, we plan to determine the toxicological effects of this guava botanical in Wistar rats. Acute oral toxicity of the extract was carried out by administration of a single dose of 5000 mg/kg body weight to female rats in 14 days. Subacute toxicity was conducted by oral administration of the extract at daily doses of 250 mg/kg, 500 mg/kg, and 1000 mg/kg body weight, respectively, while rats in the control group received no extract. After 28 days of treatment, animals were sacrificed for hematological and biochemical studies. In the acute toxicity study, no mortality or signs of toxicity were recorded; hence, the median lethal dose (LD50) of the Psidium guajava bark extract is greater than 5000 mg/kg body weight. For the subacute toxicity study, significant variations in body weight, relative weight of organs, and biochemical parameters were observed in the animals treated at different doses of the plant extract compared to control animals. Histopathological analyses showed minor liver inflammation in females treated at the highest dose (1000 mg/kg). These results suggest that intake of a single high dose of the Psidium guajava bark extract is nontoxic, but repeat administration could exhibit mild organ toxicity.

scholarly journals EFFICACY OF IVERMECTIN AGAINST GASTROINTESTINAL NEMATODIASIS AND ECTOPARASITES IN CROSSBRED CATTLE IN BANGLADESH

2017 ◽  
Vol 14 (2) ◽  
pp. 191-197
Author(s):  
M. Ahammed ◽  
M. A. Ali ◽  
M. A. Ehsan ◽  
M. Mostafa
Keyword(s):  
Body Weight ◽  
Treatment Period ◽  
Hematological Parameters ◽  
Research Work ◽  
Live Weight ◽  
Treated Group ◽  
Post Treatment ◽  
Control Group ◽  
Crossbred Cattle ◽  
Group A

The experiment was carried out to determine the efficacy of Ivermectin (Ivomec® S/C Formulation) against gastrointestinal nematodiasis and ectoparasites including stephanofilaria on crossbred cattle, to determine the effect of drug on certain hematological parameters like hemoglobin (Hb) content, packed cell volume (PCV) and erythrocyte sedimentation rate (ESR)in crossbred cattle and to determine the effect of the drug on live weight. A total of 100 cattle were selected randomly and examined for presence of both endo and ectoparasites including stephanofilaria. Gastrointestinal nematodiasis were detected by examination of fecal samples and ectoparasites as well as stephanofilaria were detected by physical examination. Out of 100 cattle, 20 were found to suffer from both endo and ectoparasites. These 20 cattle were selected finally for the research work. Then these cattle were divided into two groups, group A (treated group, n=15) and group B (control group, n=5). Ivermectin was injected subcutaneously to the cattle of group A @ 200µm/kg body weight (1ml/50 kg body weight). The therapeutic efficacy of the drug against gastrointestinal nematodiasis was determined by investigation of fecal egg count reduction and the efficacy was 100% against the common nematodes in crossbred cattle on day 7, 14, 21 and 28 of post treatment period. Ticks within a markable area (25 square inches) were counted on day 0 and lice infestation was marked as infected on day 0. Ivermectin showed 100% effectiveness at the 7, 14, 21 and 28 day of post treatment period against both tick and lice infestation. The efficacy of the drug against stephanofilariasis (humpsore) was determined by reduction of diameter of the sore on the day 14, 42 and 56 of post treatment period. All the sores were completely healed up by the 56 days. During the study of hematological parameters it was seen that Hb and PCV were increased whereas ESR values were decreased on post treatment days. In this study the mean live weight of the cattle of treated group was increased after treatment with ivermectin and increased body weight was 5.13% on the 28th day of post treatment period. From the above findings it may be concluded that ivermectin was 100% effective against gastrointestinal nematodes common in crossbred cattle. Effectiveness of the drug against external parasites was 100%. In this study hematological parameters were changed significantly after treatment with ivermectin, body weight of animal treated with ivermectin was increased and no adverse effect of the drug was found in this study.

scholarly journals Effect of Diclofenac Sodium in Broilers

2015 ◽  
Vol 13 (1) ◽  
pp. 19-24
Author(s):  
R Akter ◽  
MAW Sarker
Keyword(s):  
Body Weight ◽  
Serum Creatinine ◽  
Diclofenac Sodium ◽  
Post Treatment ◽  
Control Group ◽  
High Dose ◽  
Broiler Chicks ◽  
Serum Urea ◽  
Group A ◽  
Group B

This study was conducted to determine the effects of diclofenac sodium in broiler chicks during the period from 20th July /2012 to 1st september/2012. The broiler chicks were divided into four groups A, B, C and control with ten day old bird in each. Group A was treated with @ 5mg/kg body weight, group B was treated with @ 10mg/kg body weight and Group C was treated with 20 mg/kg body weight given orally mixing with drinking water. Histopathological, hematological and biochemical tests were performed on 42th days of age to evaluate diclofenac-induced changes between control and treated groups. Mortality rate and pathomorphological changes were observed in dead birds. The acute toxicity was assessed by observing the clinical signs and symptoms, mortality, alterations in blood biochemistry, and necropsy findings. The birds of Group A showed only mild symptoms of diarrhea and 30% mortality. In Group B, 60% and Group 70% of birds died in between 24 and 36 h post-treatment showing the symptoms of segregatory behavior, lethargy, terminal anorexia, and severe bloody diarrhea. Observation of hematological parameters like TEC, Hb, PCV and ESR on 42th days of age showed significant (p<0.01) decrease in treatment group compare to control group. Observation of biochemical parameters (serum urea, serum creatinine) on 42th days of age showed significantly increased (p<0.01) serum urea and serum creatinine indicating nephrotoxicity in broilers. At 12 and 24 h post-treatment this returned to the normal levels. The dead birds of the high-dose group also showed similar pattern of biochemical changes at 12 and 24 h post-treatment and revealed extensive visceral gout with characteristic histopathological lesions in liver, kidney, heart, spleen and intestine on post-mortem. The results indicate that diclofenac sodium has hepatotoxic, nephrotoxic, and visceral gout inducing potentials in broilers (cob-500), especially at higher dose.DOI: http://dx.doi.org/10.3329/bjvm.v13i1.23710Bangl. J. Vet. Med. (2015). 13 (1): 19-24

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