scholarly journals Improved up-and-down procedure for acute toxicity measurement with reliable LD50 verified by typical toxic alkaloids and modified Karber method

2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Yan-Yu Zhang ◽  
Yu-Feng Huang ◽  
Jie Liang ◽  
Hua Zhou

Abstract Background Up-and-down procedure (UDP) was recommended to replace traditional acute toxicity methods. However, it was limited due to the long experimental period (20–42 days). To improve UDP, an improved UDP method (iUDP) was developed by shortening observation time between sequence dosages. The aim of this study was to test the reliability of iUDP to provide a reliable method for the acute toxicity measurement of valuable or minor amount compounds. Methods Oral median lethal dose (LD50) of nicotine, sinomenine hydrochloride and berberine hydrochloride were measured both by iUDP and modified Karber method (mKM). Results LD50 of the three alkaloids measured by iUDP with 23 mice were 32.71 ± 7.46, 453.54 ± 104.59, 2954.93 ± 794.88 mg/kg, respectively. LD50 of the three alkaloids measured by mKM with 240 mice were 22.99 ± 3.01, 456.56 ± 53.38, 2825.53 ± 1212.92 mg/kg, respectively. The average time consumed by the two methods were 22 days and 14 days respectively. Total grams of the alkaloids used by the two methods were 0.0082 and 0.0673 (nicotine), 0.114 and 1.24 (sinomenine hydrochloride), 1.9 and 12.7 (berberine hydrochloride). Conclusion iUDP could replace mKM to detect acute toxicity of substances with comparable and reliable result. And it is suitable for valuable or minor amount substances.

2021 ◽  
Author(s):  
Yan-Yu Zhang ◽  
Yu-Feng Huang ◽  
Jie Liang ◽  
Hua Zhou

Abstract Background: Up-and-down procedure (UDP) was recommended to replace traditional acute toxicity methods. However, it was limited due to the long experimental period (20 - 42 days). To improve UDP, an improved UDP method (iUDP) was developed by shortening observation time between sequence dosages. The aim of this study was to test the reliability of iUDP to provide a reliable method for the acute toxicity measurement of valuable or minor amount compounds. Methods: Oral median lethal dosage (LD50) of nicotine, sinomenine hydrochloride and berberine hydrochloride were measured both by iUDP and modified Karber method (mKM). Results: LD50 of the three alkaloids measured by iUDP with 23 mice were 32.71 ± 7.46, 453.54 ± 104.59, 2954.93 ± 794.88 mg/kg, respectively. LD50 of the three alkaloids measured by mKM with 240 mice were 22.99 ± 3.01, 456.56 ± 53.38, 2825.53 ± 1212.92 mg/kg, respectively. The average time consumed by the two methods were 22 days and 14 days respectively. Total grams of the alkaloids used by the two methods were 0.0082 and 0.0673 (nicotine), 0.114 and 1.24 (sinomenine hydrochloride), 1.9 and 12.7 (berberine hydrochloride). Conclusion: iUDP could replace mKM to detect acute toxicity of substances with comparable and reliable result. And it was suitable for valuable or minor amount substances.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1660
Author(s):  
Svetlana Alipkina ◽  
Elena Kornienko ◽  
Denis Nalobin ◽  
Alexander Osmolovskiy

The different effects on animals of the thrombolytic protease complex of the new producer S. strictum 203 were studied. The tests of acute toxicity, immunotoxicity and allergenicity should conclude that the studied proteolytic complex is safe for medical usage. For the intravenous and the intraperitoneal routes of administration, the maximum tolerated dose and the median lethal dose were not determined.


2020 ◽  
pp. 31-32
Author(s):  
Mikhail A. Levchenko ◽  
◽  
Natalia A. Sennikova ◽  

Toxicological assessment is a mandatory research step in the development of new insecticidal drugs. At the All-Russian Research Institute of Veterinary Entomology and Arachnology, a prototype of the insecticidal bait Mukhnet IF was obtained with an active ingredient content of 0.06% ivermectin and 0.015% fipronil, which showed a highly effective effect against houseflies. This work presents the results of the study of acute oral toxicity of the above agent. For this, male white mice with a live weight of 16-26 g were selected. They were kept on a starvation diet for one day in individual houses with water. The drug was given in mg/kg body weight the next day. A total of 33 doses have been tested, ranging from 100 mg/kg to 40,000 mg/kg. The animals were observed for 14 days. According to the research results, it was revealed that at doses up to 20,000 mg/kg there were no signs of intoxication, but when tested at 25,000 mg/kg in some mice, these signs were noted, and at 30,000, 35,000 and 40,000 mg/kg deaths were recorded 20±10, 45±30 and 60±20%, respectively. It was not possible to test the drug over the last above dose due to incomplete eaten by mice. According to the degree of danger for warm-blooded animals, the drug belongs to the 4th class of low-hazard drugs (average lethal dose of 5000 mg/kg or more) in accordance with the classification of GOST 12.1.007-76. When analyzing the literature data on the toxicological characteristics of preparations containing ivermectin and chlorfenapyr, it was revealed that the insecticidal agent in its acute toxicity for warm-blooded animals is comparable to known analogues.


Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 654
Author(s):  
Vellingiri Manon Mani ◽  
Arockiam Jeyasundar Parimala Gnana Soundari ◽  
Balamuralikrishnan Balasubramanian ◽  
Sungkwon Park ◽  
Utthapon Issara ◽  
...  

Cervical cancer, as the most frequent cancer in women globally and accounts almost 14% in India. It can be prevented or treated with vaccines, radiation, chemotherapy, and brachytherapy. The chemotherapeutic agents cause adverse post effects by the destruction of the neighboring normal cells or altering the properties of the cells. In order to reduce the severity of the side effects caused by the chemically synthesized therapeutic agents, the current research developed an anti-cancer agent dimer of epicatechin (DoE), a natural bioactive secondary metabolite (BSM) mediated from an endophytic fungus Curvularia australiensis FC2AP. The investigation has initiated with the evaluation of inhibiting the angiogenesis which is a main activity in metastasis, and it was assessed through Hen’s Egg Test on Chorio Allantoic Membrane (HET-CAM) test; the BSM inhibited the growth of blood vessels in the developing chick embryo. Further the DoE was evaluated for its acute toxicity levels in albino mice, whereas the survival dose was found to be 1250 mg/kg and the lethal dose was 1500 mg/kg body weight of albino mice; hematological, biochemical, and histopathological analyses were assessed. The anti-inflammatory responses of the DoE were evaluated in carrageenan induced Wistar rats and the reduction of inflammation occurred in a dose-dependent manner. By fixing the effective dose for anti-inflammation analysis, the DoE was taken for the anti-cervical cancer analysis in benzo (a) pyrene induced female Sprague-Dawley rats for 60 days trial. After the stipulated days, the rats were taken for hematological antioxidants, lipid peroxidation (LPO), member bound enzymes, cervical histopathological and carcinogenic markers analyses. The results specified that the DoE has the capability of reducing the tumor in an efficient way. This is the first report of flavonoid-DoE production from an endophytic fungus C. australiensis has the anticancer potentiality and it can be stated as anti-cancer drug.


2002 ◽  
Vol 12 (2) ◽  
pp. 137-147 ◽  
Author(s):  
G. E. Kelly ◽  
J. K. Lindsey

2015 ◽  
Vol 96 (2) ◽  
pp. 208-213
Author(s):  
N Yu Alimzhanov ◽  
I Sh Chakeev ◽  
Sh Zh Zhorobekova ◽  
I O Kudaybergenova ◽  
B N Lepshin

Aim. To determine the acute toxicity and hazard class of nanosized low-esterified beet pectin.Methods. To study the acute toxicity of substances, Kerber’s method was used. Probit analysis for different values of lethal dose calculated by least squares method, as well as morphologic studies, statistical analysis (non-parametric methods - Wilcoxon-Mann-Whitney test) were used. Pectin toxicity was studies on 40 mature Wistar rats of both gender and body weight of 160-230 g.Results. Enteral administration of 12 000 mg/kg of pectin did not affect the general condition and did not lead to lethal outcome. The following values of lethal doses were calculated using probit analysis: LD16=34 990.6542056074≈35 g/kg, LD50=74 242.9906542057≈74 g/kg, LD84=113 495.327102804≈113 g/kg, LD100=133 121.495327103≈133 g/kg. Histological study of rat organ tissues that received 12 000 mg/kg of pectin showed no structural changes in tissues of examined organs. Study drug - nanosized low molecular weight pectin, might be referred to hazard class IV (low hazard substances) according to GOST 12.1.007-76. and classification K.K. Sidorov Pectin substance may be considered as practically nontoxic drug (LD50 >10,000 mg/kg), which corresponds to Class V compounds according to Hodge and Sterner classification and classification by K.K. Sidorov.Conclusion. The results indicate complete safety of nanosized forms of pectin, which opens up prospects for further studies of the biological properties of this substance.


2017 ◽  
Vol 4 (1) ◽  
pp. 42
Author(s):  
Ira Safitri ◽  
Inayah Inayah

Sapu Jagad (Isotoma longiflora (L) Presl.) plant has been empirically used as traditional medicine. Some studies showthat this plant has pharmacological effects as antibiotic, anticancer, and analgetic. It is of importance to conduct studyin finding out the safetiness of this plant as herbal medicine. Therefore, we conducted study to find out lethal dose ofits leaves on mice (Mus muculus) using acute toxicity test. Several doses have been given to certain groups to find outits effect including death. The extract has been given one time per oral. Then, we recorded the clinical signs and deathof mice until 14 days. The data was analyzed using probit analysis to measure LD50. This study shows that ethanolextract of Sapu Jagad leaves has LD50 12.610 mg/kgBW and toxicity of central nervous system proven by seizureending with death. As conclusion, this extract has toxicity especially to central nervous system.


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