Telomere attrition may be a more realistic toxicity test for both low and high dose exposure

2021 ◽  
pp. 103788
Author(s):  
Ayse Basak ENGIN ◽  
Michael D. COLEMAN
Keyword(s):  
Toxicity Test ◽  
High Dose ◽  
Telomere Attrition

scholarly journals SUBCHRONIC TOXICITY TEST OF COMBINATION ETHANOL EXTRACT OF DETAM 1 SOYBEAN (GLYCINE MAX L. MERR) AND JATI BELANDA (GUAZUMA ULMIFOLIA LAMK) TOWARD FUNCTION, WEIGHT, AND HISTOPATHOLOGICAL OF WISTAR RAT LIVER

2016 ◽  
Vol 9 (5) ◽  
pp. 197
Author(s):  
Meilinah Hidayat ◽  
Sijani Prahastuti ◽  
Estherolita Dewi ◽  
Dewi Safitri ◽  
Siti Farah Rahmawati ◽  
...  
Keyword(s):  
Liver Function ◽  
Toxicity Test ◽  
Low Dose ◽  
Ethanol Extract ◽  
Good Effect ◽  
Control Group ◽  
High Dose ◽  
Subchronic Toxicity ◽  
Treatment Groups ◽  
Significant Difference

ABSTRACTObjective: As an antiobesity therapy, combination extracts of Detam 1 soybean and Jati Belanda will be consumed for a long time; therefore, theirtoxicities to the liver need to be investigated. To determine the effect of subchronic toxicity test of combination of ethanol extract of Detam 1 soybean(EEDS) and ethanol extract of Jati Belanda (EEJB) on liver function with parameters: Alanine transaminase (ALT), macroscopic, and histopathologicalof liver.Methods: This study was conducted on 120 Wistar rats (60 males and 60 females), 90 days (treatment group) and 120 days (satellite group). Ratswere divided into six treatment groups (3 test materials, 1 control, and 2 satellites); each group included 10 males and 10 females.Results: ALT levels of treatment groups (low dose, medium, and high), both males and females were lower than the control group (p<0.05). Thetreatment groups demonstrated a good effects effect on liver function. Liver weight of all groups showed no significant difference compared with thecontrol group (p>0.05). Results of histopathological score interpretation of male and female liver rats of low dose groups were not disturbed; middledose groups were slightly disturbed and high dose groups were damaged. Satellite high doses of male groups were disrupted, while female groupswere not.Conclusion: The combination of EEDS and EEJB has a good effect on liver function, did not lead to change organ weight and at low doses did not causerenal histopathology damage in rats after 90 days administration.Keywords: Combination of soybean Jati Belanda, Toxicity subchronic test, Function, Weight, Histopathology, Liver.

​Safety Evaluation of Andrographolide-nanosuspensions

2021 ◽  
Author(s):  
Haigang Wu ◽  
Jia Liu ◽  
Zhaowei Ye ◽  
Jinni Liu ◽  
Li Huang ◽  
...  
Keyword(s):  
Toxicity Test ◽  
Dose Group ◽  
In Vitro Release ◽  
Liver Cells ◽  
Precipitation Method ◽  
Hepatic Veins ◽  
High Dose ◽  
Interstitial Tissue ◽  
Renal Tubules ◽  
Cell Counts

Background: Andrographolide (ANDRO) is a hydrophobic drug, which faces the problem of limited absorption due to poor water solubility. The current research prepared andrographolide nanosuspensions (ANDRO-NS) and examined in vivo toxicity for mice. Methods: ANDRO-NS were prepared by anti-solvent precipitation method, transmission electron micrographs, granularity analysis and in vitro release were used to characterize the ANDRO-NS, we evaluate the safety of the ANDRO-NS by using the acute toxicity test, local irritation test and chronic toxicity test. Result: The particle size of ANDRO-NS was (568.51±13.74 nm). The LD50 for ANDRO-NS was 548.91 mg/kg after oral administration to KM mice with a 95% CI of 468.19-645.03 mg/kg. The white blood cell counts and hemoglobin levels for the experimental groups were lower than controls receiving only saline. Serum aspartate transaminase, creatinine and blood urea nitrogen levels were greater than controls after 7 and 14 days of once-daily administration. After 14 days of administration, the platelet counts as well asalanine transaminase levels were, in addition, Histological observations indicated that interstitial kidney tissues were wider than controls and showed episodic bleeding after 7 days of administration. The highest dose administered also resulted in the dilation and blood engorgement of the central hepatic veins with some severed hepatic cords. Mice receiving the lowest dose of ANDRO-NS we administered appeared healthy and similar to controls receiving saline only. Following 14 days of administration, we found significant vacuolar degeneration of renal tubular epithelial cells and glomerular atrophy for the high-dose group as well as edema and necrosis in liver cells. The medium-dose group displayed kidney interstitial tissue widening with scattered bleeding, inflammatory cell infiltration and hepatocyte edema. The low-dose group displayed dilated renal tubules and irregularly-arranged liver cells as well as bleeding in the hepatic sinusoids. Therefore, short-term administration of andrographolide suspensions resulted in inflammation and time- and dose-dependent toxic effects on the kidneys and liver.

scholarly journals 14-Day Repeated Intraperitoneal Toxicity Test of Ivermectin Microemulsion Injection in Wistar Rats

2020 ◽  
Vol 7 ◽  
Author(s):  
Zhen Dong ◽  
Shou-ye Xing ◽  
Ji-yu Zhang ◽  
Xu-zheng Zhou
Keyword(s):  
Toxicity Test ◽  
Wistar Rats ◽  
Histopathological Examination ◽  
Clinical Chemistry ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Toxic Injury ◽  
Male And Female Rats ◽  
Initial Stage

To evaluate the safety of ivermectin microemulsion injection, 100 Wistar rats were injected intraperitoneally at 0.38 g/kg, 0.19 g/kg, and 0.1 g/kg for 14 days. The 14-day repeated toxicity test of ivermectin microemulsion injection was systematically evaluated by clinical observation, organ coefficient, hematological examination, clinical chemistry examination, and histopathological examination. The results showed that no rats died during the test. At the initial stage of treatment, the rats in the high dose group had mild clinical reaction, which disappeared after 4 days. Clinical chemistry showed that the high dose of ivermectin microemulsion could cause significant changes in ALT and LDH parameters in male rats; high and medium doses could increase the liver coefficients of male and female rats. The toxic target organ may be the liver as indicated by histopathological findings. No significant toxic injury was found in the heart, liver, spleen, lung, kidney, brain, ovary, and testes of all groups of rats. No drug-related toxic effects were found at low doses, and thus the NOVEL of ivermectin microemulsion injection was 0.19 g/kg.

THE HEMATOLOGIC PROFILE IN THE ACUTE TOXICITY TEST OF COGON GRASS ROOTS ETHANOL EXTRACT IN WISTAR RATS

2020 ◽  
pp. 72-75
Author(s):  
VANESSA AYU SUMIRAT ◽  
IRMA MELYANI PUSPITASARI ◽  
NENI ANGGRAENI ◽  
MAS RIZKY ANGGUN ADIPURNA SYAMSUNARNO
Keyword(s):  
Acute Toxicity ◽  
Toxicity Test ◽  
Wistar Rats ◽  
Ethanol Extract ◽  
Female Rats ◽  
Control Group ◽  
High Dose ◽  
Acute Toxicity Test ◽  
Grass Roots ◽  
Hematologic Profile

Objective: This study aimed to investigate the hematologic profile of Wistar rats in the acute toxicity test of Cogon grass roots ethanol extract (CGEE). Methods: Cogon grass roots were dissolved in 70% ethanol. An acute toxicity test was conducted based on The National Agency of Drug and Food Control of the Republic of Indonesia. Five female rats in the treatment group were administered a single high dose of 5000 mg/kg body weight (BW) of CGEE in 200 μl of 0.5% carboxymethyl cellulose (CMC), and the 5 female rats in the control group were administered 200 μl of 0.5% CMC. After 14 d, blood samples were collected, and 18 hematologic parameters were measured with a hematology analyzer. Statistical analyses were performed to compare the parameters between the two groups with the independent t-test for normally distributed data and the Mann Whitney test for non-normally distributed data. Results: None of the hematologic parameters in the treatment group significantly differed from those in the control group after 14 d of observation (P>0.05). Conclusion: A single high dose of 5000 mg/kg BW of CGEE did not change the hematologic profile of Wistar rats. These results indicate that CGEE does not have an acute hemotoxic effect, at least for hematologic parameters.

scholarly journals The Climbing Performance, Neuromuscular Transmitter (ACHE) Activity, Reproductive Performance and Survival of Drosophila melanogaster Fed Diet with Mangifera indica Cold Aqueous Leaf Extract

2019 ◽  
pp. 1-11
Author(s):  
Etuh Monday Alexander ◽  
John Chinyere Aguiyi ◽  
Iorjiim Walter Mdekera ◽  
Ochala Sunshine Ogwu ◽  
Oyeniran Oluwatosin Imoleayo ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Acute Toxicity ◽  
Toxicity Test ◽  
Leaf Extract ◽  
Mangifera Indica ◽  
High Dose ◽  
Slight Reduction ◽  
Distilled Water ◽  
Phytochemical Screening ◽  
Aqueous Leaf Extract

Objective: To screen the toxic effect of Mangifera indica aqueous leaf extract in Drosophila melanogaster. Materials and Methods: Phytochemical screening was carried out. 20 Adult flies were exposed to 7.5 mg, 15 mg,  30 mg, 45 mg and 100 mg /10 g diet for acute toxicity (168hrs) while 50 flies were exposed to 2.5 mg, 5 mg and 10 mg/10 g diet for sub chronic (28 days). All concentrations were prepared in 1000µl of distilled water and replicated three (3) times. Diet+1000µl of Distilled water served as control. Fecundity/developmental toxicity, Climbing and AChE activities were carried out by exposing flies to the sub-chronic concentrations for 5 days. Results: Phytochemical screening revealed the presence of alkaloids, phenols, flavonoids, tannins, saponins and terpenoids. The acute toxicity test showed 100% mortality at 100 mg/ 10 g diet and 168hrs LC50 was 72.4 mg/10 g diet. The sub chronic toxicity test showed decrease in flies survival along concentration with a least survival at 10 mg/10 g diet. There was a slight reduction and elevation in the Climbing and AChE activities respectively but not statistically significant (p>0.05) compared to control. At 5 mg and 10 mg/10 g diet there was a delay in the development with few emerged flies. Conclusion: From the Results, it can be concluded that Mangiferaindica aqueous leaf extract may be toxic at high dose from 72.4 mg/10 g diet and might have an adverse effect on the development and survival of flies at sub chronic concentration as low as 2.5 mg/10g diet.

Influence of High-Dose Verapamil on Beagle Lens Proteins (Chronic Toxicity Test)

1986 ◽  
Vol 18 (4) ◽  
pp. 215-223 ◽  
Author(s):  
J. Bours ◽  
O. Hockwin ◽  
W. Schnitzlein ◽  
G. Löhnert
Keyword(s):  
Toxicity Test ◽  
Chronic Toxicity ◽  
High Dose ◽  
Lens Proteins ◽  
Chronic Toxicity Test

scholarly journals IMPACT OF Pleurotus tuber-regium (Rumph. ex Fr.) EXTRACT-LOADED NANOPARTICLES ON THYROID PROFILE OF RATS

2021 ◽  
Vol 14 (3) ◽  
pp. 62-66
Author(s):  
Sukumar Dandapat ◽  
Keyword(s):  
Silver Nanoparticles ◽  
Acute Toxicity ◽  
Toxicity Test ◽  
Assay Method ◽  
Control Group ◽  
High Dose ◽  
Acute Toxicity Test ◽  
Animal Group ◽  
Thyroid Profile ◽  
The Impact

Aim. The aim of this study was to investigate the impact of Pleurotus tuber-regium extract loaded silver nanoparticles (SNPs) on thyroid profile of rats. Methods. Acute toxicity test was performed following up and down procedure and the analysis of thyroid profile was performed following chemiluminescence assay method. Results. Acute toxicity test showed no mortality and no behavioral changes in rats treated with 2000 mg kg-1 of SNPs. High dose (400 mg kg-1) of SNPs showed high hyper thyroid activity by increasing T3 = 38.20±4.06 ng dL-1; T4 = 4.40±0.32µg dL-1; and by decreasing TSH = 0.73±0.06µIU mL-1 compared to control group (T3 = 30.20±1.02 ng dL-1; T4 = 2.94±0.08µg dL-1; TSH = 0.87±0.01µIU mL-1) and animal group treated with 200 mg kg-1 dose of SNPs (T3 = 35.69±1.13 ng dL-1; T4 = 3.82±0.24µg dL-1; TSH = 0.80±0.02µIU mL-1). Conclusions. Pleurous tuber-regium extract loaded silver nanoparticles are non toxic and can be used in drug delivery as well as in the formulation of drugs used in hypothyroidism.

Electron Beam Damage of Biomolecules Assessed by Energy Loss Spectroscopy

1978 ◽  
Vol 36 (3) ◽  
pp. 61-69
Author(s):  
M. Isaacson ◽  
M.L. Collins ◽  
M. Listvan
Keyword(s):  
Electron Microscopy ◽  
Radiation Damage ◽  
Structural Integrity ◽  
Analytical Electron Microscopy ◽  
High Dose ◽  
Dose Rates ◽  
Special Cases ◽  
Analytical Electron ◽  
Atom Migration ◽  
Beam Damage

Over the past five years it has become evident that radiation damage provides the fundamental limit to the study of blomolecular structure by electron microscopy. In some special cases structural determinations at very low doses can be achieved through superposition techniques to study periodic (Unwin & Henderson, 1975) and nonperiodic (Saxton & Frank, 1977) specimens. In addition, protection methods such as glucose embedding (Unwin & Henderson, 1975) and maintenance of specimen hydration at low temperatures (Taylor & Glaeser, 1976) have also shown promise. Despite these successes, the basic nature of radiation damage in the electron microscope is far from clear. In general we cannot predict exactly how different structures will behave during electron Irradiation at high dose rates. Moreover, with the rapid rise of analytical electron microscopy over the last few years, nvicroscopists are becoming concerned with questions of compositional as well as structural integrity. It is important to measure changes in elemental composition arising from atom migration in or loss from the specimen as a result of electron bombardment.

Electron-diffraction studies in synthetic polymer materials

1983 ◽  
Vol 41 ◽  
pp. 362-365
Author(s):  
D.T. Grubb
Keyword(s):  
Electron Diffraction ◽  
Synthetic Polymer ◽  
Polymer Materials ◽  
Crystallographic Structure ◽  
High Dose ◽  
Electron Dose ◽  
Dose Rates ◽  
First Case ◽  
Diffraction Patterns ◽  
The Many

Diffraction studies in polymeric and other beam sensitive materials may bring to mind the many experiments where diffracted intensity has been used as a measure of the electron dose required to destroy fine structure in the TEM. But this paper is concerned with a range of cases where the diffraction pattern itself contains the important information.In the first case, electron diffraction from paraffins, degraded polyethylene and polyethylene single crystals, all the samples are highly ordered, and their crystallographic structure is well known. The diffraction patterns fade on irradiation and may also change considerably in a-spacing, increasing the unit cell volume on irradiation. The effect is large and continuous far C94H190 paraffin and for PE, while for shorter chains to C 28H58 the change is less, levelling off at high dose, Fig.l. It is also found that the change in a-spacing increases at higher dose rates and at higher irradiation temperatures.

Microprobe analysis of inclusion bodies related to two benzofuran derivatives

1987 ◽  
Vol 45 ◽  
pp. 672-673
Author(s):  
T. L. Benning ◽  
P. Ingram ◽  
J. D. Shelburne
Keyword(s):  
Inclusion Bodies ◽  
Uranyl Acetate ◽  
Multiple Organ ◽  
High Dose ◽  
En Bloc ◽  
Tissue Samples ◽  
Transmission Electron ◽  
Organ Systems ◽  
Dense Inclusion ◽  
Melanin Complex

Two benzofuran derivatives, chlorpromazine and amiodarone, are known to produce inclusion bodies in human tissues. Prolonged high dose chlorpromazine therapy causes hyperpigmentation of the skin with electron-dense inclusion bodies present in dermal histiocytes and endothelial cells ultrastructurally. The nature of the deposits is not known although a drug-melanin complex has been hypothesized. Amiodarone may also cause cutaneous hyperpigmentation and lamellar lysosomal inclusion bodies have been demonstrated within the cells of multiple organ systems. These lamellar bodies are believed to be the product of an amiodarone-induced phospholipid storage disorder. We performed transmission electron microscopy (TEM) and energy dispersive x-ray microanalysis (EDXA) on tissue samples from patients treated with these drugs, attempting to detect the sulfur atom of chlorpromazine and the iodine atom of amiodarone within their respective inclusion bodies.A skin biopsy from a patient with hyperpigmentation due to prolonged chlorpromazine therapy was fixed in 4% glutaraldehyde and processed without osmium tetroxide or en bloc uranyl acetate for Epon embedding.

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