Ensemble machine learning to evaluate the in vivo acute oral toxicity and in vitro human acetylcholinesterase inhibitory activity of organophosphates

The objective of this work was to evaluate the antiplasmodial activity and toxicity of the extract and fractions obtained from the bark of Aspidosperma nitidum. The ethanol extract obtained from the powdered bark of plants was acid-base partitioned and phytochemically analyzed. The antiplasmodial activity, in vivo antimalarial activity and in vitro cytotoxicity were acessed. The selectivity index (SI) was calculated. The acute oral toxicity and pathological effects, of the ethanol extract was evaluated in mice. The major constituent of the ethanol extract was suggestive of a β-carboline chromophore. The alkaloid and neutral fractions contained compounds with an aspidospermine core as the major constituent. The ethanol extract (IC50 = 3.60 µg/mL), neutral fraction (IC50 = 3.34 µg/mL) and alkaloid fraction (IC50= 2.32 µg/mL) showed high activity against P. falciparum (W2 strain). The ethanol extract and the alkaloid fraction reduced 80% of the parasitemia of P. berghei (ANKA)-infected mice (dose of 500 mg/kg) in the 5th day, which was not sustainable at the 8th day. A similar result was obtained for chloroquine. The ethanol extract (CC50 = 410.65 µg/mL; SI = 114.07), neutral fraction (CC50 = 452.53 µg/mL; SI = 135.49), and alkaloid fraction (CC50 =346.73 µg/mL; SI 149.45) demonstrated low cytotoxicity and high SI. The ethanol extract (5000 mg/kg; gavage) presented low acute oral toxicity, with no clinical or anatomopathological modifications being observed (in comparison to the control group). In vitro studies with a chloroquine-resistant clone of P. falciparum confirmed the antiplasmodial activity of the A. nitidum ethanol extract, and its fractions had low cytotoxicity for HepG2 cells. In vivo studies with P. berghei–infected mice and acute toxicity studies corroborated these results.

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Acute, subacute oral toxicity and Ames test of Py-mulin: an antibacterial drug candidate

BMC Pharmacology and Toxicology ◽

10.1186/s40360-021-00543-5 ◽

2022 ◽

Vol 23 (1) ◽

Author(s):

Yuan Fan ◽

Yunxing Fu ◽

Yuhang Zhou ◽

Yu Liu ◽

Baocheng Hao ◽

...

Keyword(s):

Ames Test ◽

Clinical Chemistry ◽

Toxicity Study ◽

Female Rats ◽

Drug Candidate ◽

Antibacterial Drug ◽

Acute Oral Toxicity ◽

Oral Toxicity

Abstract Background Py-mulin is a new pleuromutilin derivative with potent antibacterial activities in vitro and in vivo, suggesting this compound may lead to a promising antibacterial drug after further development. The present study is aimed to evaluate the acute and subacute oral toxicity, and the genotoxicity with the standard Ames test according to standard protocols. Methods Acute oral toxicity of Py-mulin was determined using Kunming mice. The 28-day repeated dose oral toxicity study in SD rats was performed according to OECD guideline No. 407. The bacterial reverse mutation (Ames test) was carried out using four Salmonella typhimurium (S. typhimurium) strains TA97, TA98, TA100 and TA1535 with and without S9 metabolic activation. Results The LD50 values in acute oral toxicity were 2973 mg/kg (female mice) and 3891 mg/kg (male mice) calculated by the Bliss method. In subacute toxicity study, 50 mg/kg Py-mulin did not induce any abnormality in body weight, food consumption, clinical sign, hematology, clinical chemistry, organ weight, and histopathology in all of the treatment groups. However, high doses of Py-mulin (100 and 300 mg/kg) displayed slightly hepatotoxicity to female rats. Furthermore, Py-mulin did not significantly increase the number of revertant colonies of four standard S. typhimurium strains with the doses of 0.16–1000 μg/plate in the Ames study. Conclusions Based on our findings, our study provides some information for the safety profile of Py-mulin.

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Synthesis, crystal structure, in vitro anticancer and in vivo acute oral toxicity studies of tetramethylene linked bis-benzimidazolium salts and their respective dinuclear Ag(I)–NHC complexes

Journal of Coordination Chemistry ◽

10.1080/00958972.2016.1230670 ◽

2016 ◽

Vol 69 (22) ◽

pp. 3367-3383 ◽

Cited By ~ 7

Author(s):

Tabinda Fatima ◽

Rosenani A. Haque ◽

Mohd. R. Razali ◽

Ashfaq Ahmad ◽

Muhammad Adnan Iqbal ◽

...

Keyword(s):

Crystal Structure ◽

Acute Oral Toxicity ◽

Oral Toxicity ◽

Toxicity Studies ◽

Benzimidazolium Salts

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Acute, Multiple-Dose Dermal and Genetic Toxicity of Nu-3: A Novel Antimicrobial Agent

Journal of Biomedicine and Biotechnology ◽

10.1155/2010/362524 ◽

2010 ◽

Vol 2010 ◽

pp. 1-8

Author(s):

Juan Sun ◽

Yanxin Hu ◽

Shanping Cao ◽

Guozhong Zhang ◽

Lun-Quan Sun ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Multiple Dose ◽

Hematological Parameters ◽

Acute Oral Toxicity ◽

Antimicrobial Compound ◽

Oral Toxicity ◽

Genetic Toxicity ◽

Toxicological Profile

Nu-3 [butyl-phosphate--thymidine--phosphate-butyl] is a modified nucleotide that has been shown to have antimicrobial activity against a range of bacteria includingPseudomonas aeruginosa. However, data on the toxicological profile of Nu-3 are still lacking. In the present study, the toxicity of Nu-3 was evaluated by the following studies: acute oral toxicity, dermal and mucous membrane irritation, multiple-dose toxicity and genotoxicity in vivo and vitro. The acute oral toxicity test in mice showed that Nu-3 had an of 2001mg/kg body weight. The irritation tests on rats revealed that Nu-3 was not irritant, with an irritation scoring of 0. The multiple-dose toxicity study in rats showed that Nu-3 did not cause significant changes in histology, selected serum chemistry, and hematological parameters compared to the controls. Rats administrated with multiple-doses of Nu-3 showed no visible toxic symptoms. Both in vitro and in vivo, Nu-3 exhibited no notable genetic toxicity. Overall, the data suggest that Nu-3 is hypotoxic or nontoxic antimicrobial compound that warrants being further developed for treatingPseudomonas aeruginosainfection.

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Evaluation of the glycemic effect ofCeratonia siliquapods (Carob) on a streptozotocin-nicotinamide induced diabetic rat model

PeerJ ◽

10.7717/peerj.4788 ◽

2018 ◽

Vol 6 ◽

pp. e4788 ◽

Cited By ~ 5

Author(s):

Mousa A. Qasem ◽

Mohamed Ibrahim Noordin ◽

Aditya Arya ◽

Abdulsamad Alsalahi ◽

Soher Nagi Jayash

Keyword(s):

Blood Glucose ◽

Inhibitory Effect ◽

Diabetic Control ◽

Acute Oral Toxicity ◽

Oral Toxicity ◽

Β Cells ◽

Pancreatic Β Cells ◽

Sd Rats

BackgroundCeratonia siliquapods (carob) have been nominated to control the high blood glucose of diabetics. In Yemen, however, its antihyperglycemic activity has not been yet assessed. Thus, this study evaluated thein vitroinhibitory effect of the methanolic extract of carob pods against α-amylase and α-glucosidase and thein vivoglycemic effect of such extract in streptozotocin-nicotinamide induced diabetic rats.Methods2,2-diphenyl-1-picrylhydrazyl (DPPH) and Ferric reducing antioxidant power assay (FRAP) were applied to evaluate the antioxidant activity of carob.In vitrocytotoxicity of carob was conducted on human hepatocytes (WRL68) and rat pancreatic β-cells (RIN-5F). Acute oral toxicity of carob was conducted on a total of 18 male and 18 femaleSprague-Dawley(SD) rats, which were subdivided into three groups (n = 6), namely: high and low dose carob-treated (CS5000 and CS2000, respectively) as well as the normal control (NC) receiving a single oral dose of 5,000 mg kg−1carob, 2,000 mg kg−1carob and 5 mL kg−1distilled water for 14 days, respectively. Alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, total bilirubin, creatinine and urea were assessed. Livers and kidneys were harvested for histopathology.In vitroinhibitory effect against α-amylase and α-glucosidase was evaluated.In vivoglycemic activity was conducted on 24 male SD rats which were previously intraperitoneally injected with 55 mg kg−1streptozotocin (STZ) followed by 210 mg kg−1nicotinamide to induce type 2 diabetes mellitus. An extra non-injected group (n = 6) was added as a normal control (NC). The injected-rats were divided into four groups (n = 6), namely: diabetic control (D0), 5 mg kg−1glibenclamide-treated diabetic (GD), 500 mg kg−1carob-treated diabetic (CS500) and 1,000 mg kg−1carob-treated diabetic (CS1000). All groups received a single oral daily dose of their treatment for 4 weeks. Body weight, fasting blood glucose (FBG), oral glucose tolerance test, biochemistry, insulin and hemostatic model assessment were assessed. Pancreases was harvested for histopathology.ResultsCarob demonstrated a FRAP value of 3191.67 ± 54.34 µmoL Fe++and IC50of DPPH of 11.23 ± 0.47 µg mL−1.In vitro,carob was non-toxic on hepatocytes and pancreatic β-cells. In acute oral toxicity, liver and kidney functions and their histological sections showed no abnormalities. Carob exerted anin vitroinhibitory effect against α-amylase and α-glucosidase with IC50of 92.99 ± 0.22 and 97.13 ± 4.11 µg mL−1, respectively. In diabetic induced rats, FBG of CS1000 was significantly less than diabetic control. Histological pancreatic sections of CS1000 showed less destruction of β-cells than CS500 and diabetic control.ConclusionCarob pod did not cause acute systemic toxicity and showedin vitroantioxidant effects. On the other hand, inhibiting α-amylase and α-glucosidase was evident. Interestingly, a high dose of carob exhibits anin vivoantihyperglycemic activity and warrants further in-depth study to identify the potential carob extract composition.

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Antioxidant, Anti-Inflammatory, Acute Oral Toxicity, and Qualitative Phytochemistry of The Aqueous Root Extract of Launaea cornuta (Hochst. Ex Oliv. & Hiern.)

Journal of Evidence-Based Integrative Medicine ◽

10.1177/2515690x211064585 ◽

2021 ◽

Vol 26 ◽

pp. 2515690X2110645

Author(s):

Evans Kapanat Akimat ◽

George Isanda Omwenga ◽

Gervason Apiri Moriasi ◽

Mathew Piero Ngugi

Keyword(s):

Plant Extract ◽

Ex Vivo ◽

Radical Scavenging ◽

Root Extract ◽

Dependent Manner ◽

Acute Oral Toxicity ◽

Oral Toxicity ◽

Anti Inflammatory

The root and leaf extracts of Launaea cornuta have been locally used in traditional medicine for decades to manage inflammatory conditions and other oxidative-stress-related syndromes; however, their pharmacologic efficacy has not been scientifically investigated and validated. Accordingly, we investigated the in vitro antioxidant activity, anti-inflammatory ( in vitro, ex vivo, and in vivo) efficacy, acute oral toxicity, and qualitative phytochemical composition of the aqueous root extract of L. cornuta. The ferric-reducing antioxidant power (FRAP) and the 2,2-diphenyl-2-pycrylhydrazyl (DPPH) radical scavenging test methods were used to determine the studied plant extract’s antioxidant activity. Besides, the anti-inflammatory efficacy of the studied plant extract was investigated using in vitro (anti-proteinase and protein denaturation), ex vivo (membrane stabilization), and in vivo (carrageenan-induced paw oedema in Swiss albino mice) methods. The studied plant extract demonstrated significant in vitro antioxidant effects, which were evidenced by higher DPPH radical scavenging and FRAP activities, in a concentration-dependent manner ( p < 0.05). Generally, the studied plant extract exhibited significant in vitro, ex vivo, and in vivo anti-inflammatory efficacy, respectively, and in a concentration/dose-dependent manner compared with respective controls ( p < 0.05). Moreover, the studied plant extract did not cause any observable signs of acute oral toxicity, even at the cut-off dose of 2000 mg/Kg BW (LD50 > 2000 mg/Kg BW), and was thus considered safe. Additionally, qualitative phytochemistry revealed the presence of various antioxidant- and anti-inflammatory-associated phytochemicals, which were deemed responsible for the reported pharmacologic efficacy. Further studies to characterise bioactive molecules and their mode(s) of pharmacologic efficacy are encouraged.

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ACUTE TOXICITY TESTING OF NEWLY DISCOVERED POTENTIAL ANTIHEPATITIS B VIRUS AGENTS OF PLANT ORIGIN

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i11.20717 ◽

2017 ◽

Vol 10 (11) ◽

pp. 210 ◽

Cited By ~ 1

Author(s):

Subaiea Gm ◽

Aljofan M ◽

Devadasu Vr ◽

Alshammari Tm

Keyword(s):

Acute Toxicity ◽

Antiviral Activity ◽

Toxicity Testing ◽

Acute Oral Toxicity ◽

Isoquinoline Alkaloids ◽

Oral Toxicity ◽

B Virus ◽

Low Cytotoxicity

Objective: Our previous studies indicate that alkaloids could be developed as potential antihepatitis B agents. In the present study, we investigated the in vitro antihepatitis B virus (HBV) activity and in vivo acute oral toxicity of three isoquinoline alkaloids [-(-) Canadine, Corydadine, and Berberine] obtained from Fumaria and Corydalis species. The compounds were selected based on their therapeutic indexes calculated previously in vitro.Methods: The antiviral activity and cytotoxicity of selected isoquinoline alkaloids were evaluated in vitro in HepG2 cells. In vivo, acute oral toxicity was performed in female mice following the Organization for Economic Cooperation and Development test guideline-423 (acute toxicity class method).Results: The selected agents have shown high antiviral activity against HBV and low cytotoxicity in vitro. The results obtained from an acute oral toxicity study revealed that the LD50 of all the test compounds was >2000 mg/kg when administered orally to mice. All the tested compounds fall under the category 5 (unclassified) according to the Globally Harmonized System, with a LD50 value >2000 mg/kg when orally administered to mice.Conclusion: The results of the study revealed that OR-13 and MNAD can be studied further and can be developed as antihepatitis B drugs.

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