scholarly journals Assessment of in vivo chronic toxicity of chitosan and its derivates used as oral insulin carriers

2015 ◽  
Vol 4 (2) ◽  
pp. 281-290 ◽  
Author(s):  
Piyasi Mukhopadhyay ◽  
Sourav Bhattacharya ◽  
Arpita Nandy ◽  
Aditi Bhattacharyya ◽  
Roshnara Mishra ◽  
...  

In the present study, the chronic oral toxicity of chitosan derivates was investigated in the mice model.

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Kalay Hagazy ◽  
Gereziher G. Sibhat ◽  
Aman Karim ◽  
Gebretsadkan H. Tekulu ◽  
Gomathi Periasamy ◽  
...  

Objective. To evaluate the antimalarial effect of aqueous methanolic extract and solvent fractions of Meriandra dianthera leaves against Plasmodium berghei in mice model. Method. M. dianthera leaves were extracted with 80% methanol and dried. The dried crude extract was then defatted and further fractionated with chloroform, ethyl acetate, and butanol. Acute oral toxicity test was performed as per the Organization for Economic Cooperation and Development guideline 425. Peter’s 4-day suppressive test was used to determine the in vivo antimalarial activity of the extract and fractions. Result. The crude leaf extract of Meriandra dianthera showed parasite inhibition of 42.28% and 45.52% at doses of 400 and 600 mg/kg, respectively, as compared to the negative control. Moreover, the mice which received chloroform and aqueous fractions at the dose of 400 mg/kg/day showed significant (P<0.001) chemosuppression compared to the negative control. Both the extract and fractions were able to prevent P. berghei induced body weight loss and body temperature reduction and also increased the survival time of the mice as compared to the negative control. The aqueous methanolic leaf extract of M. dianthera showed no gross signs of toxicity or mortality in mice until a single oral dose of 2000 mg/kg. Conclusion. The extracts of M. dianthera leaves showed promising antimalarial activity, with no sign of toxicity and therefore may support its traditional use for the treatment of malaria.


2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Chatchai Chaotham ◽  
Songpol Chivapat ◽  
Anan Chaikitwattana ◽  
Wanchai De-Eknamkul

Plaunotol, an acyclic diterpenoid with highly effective antigastric ulcer properties, has been commercially isolated from leaves ofCroton stellatopilosusOhba. This Thai medicinal plant was traditionally used in the form of crude extracts, suggesting that it is possible to administer these plaunotol-containing extracts without toxicity. To confirm its safety, the oral toxicity of a partially purified plaunotol extract (PPE) was evaluatedin vivo. The PPE was simply prepared by 95% ethanol reflux extraction followed by hexane partition. The obtained extract was analyzed and found to contain 43% w/w of plaunotol and another compound, likely a fatty acid-plaunotol conjugate that is considered a major impurity. Oral administration of PPE to ICR mice and Wistar rats was conducted to evaluate acute and chronic toxicity of the plaunotol extract, respectively. The acute toxicity study demonstrated that PPE was practically nontoxic based on its high median lethal dose value (LD50=10.25 g/kg). The chronic toxicity studies also showed the absence of mortality and clinical symptoms in all rats treated with 11–1,100 mg/kg/day of PPE during a 6-month period. Histopathological and hematological analyses revealed that altered liver and kidney function and increased blood platelet number, but only at the high doses (550–1,100 mg/kg/day). These results suggest that PPE is potentially safe for further development as a therapeutic agent in humans.


2020 ◽  
Vol 9 (4) ◽  
pp. 484-492
Author(s):  
Sini Kang ◽  
Tony V Johnston ◽  
Seockmo Ku ◽  
Geun Eog Ji

Abstract B-FOS (butyl-fructooligosaccharide) is a newly synthesized prebiotic molecule, formed by the combination of FOS and butyrate by ester bonds. B-FOS has been reported to have the potential prebiotic effect of promoting intestinal flora diversity and enhancing butyrate production. The aim of this study was to investigate the potential acute and sub-chronic toxicity of B-FOS in Institute of Cancer Research (ICR) mice and Wistar rats to verify its biosafety. ICR mice were administered a single oral gavage of B-FOS at doses of 0, 500, 1000, and 2000 mg/kg body weight and observed for signs of acute toxicity for 14 days. Sub-chronic toxicity was evaluated by repeated oral administration of B-FOS at 2000 mg/kg for 28 days, in accordance with Organization for Economic Co-operation and Development (OECD) protocol test numbers 420 and 407. No mortality or abnormal clinical signs were observed during the experimental periods after B-FOS administration. Furthermore, no significant changes in body weight, organ weight, serum biochemical parameters, or tissue histology were observed after animal sacrifice. These in vivo results indicate that B-FOS does not exert any acute or sub-chronic toxicity at a dose of 2000 mg/kg, and this novel molecule can be regarded as a safe prebiotic substance for use in the food and nutraceutical industries.


Toxins ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 489
Author(s):  
Andrea Boente-Juncal ◽  
Sandra Raposo-García ◽  
Carmen Vale ◽  
M. Carmen Louzao ◽  
Paz Otero ◽  
...  

Palytoxin (PLTX) is one of the most poisonous substances known to date and considered as an emergent toxin in Europe. Palytoxin binds to the Na+-K+ ATPase, converting the enzyme in a permeant cation channel. This toxin is known for causing human fatal intoxications associated with the consumption of contaminated fish and crustaceans such as crabs, groupers, mackerel, and parrotfish. Human intoxications by PLTX after consumption of contaminated fishery products are a serious health issue and can be fatal. Different reports have previously explored the acute oral toxicity of PLTX in mice. Although the presence of palytoxin in marine products is currently not regulated in Europe, the European Food Safety Authority expressed its opinion on PLTX and demanded assessment for chronic toxicity studies of this potent marine toxin. In this study, the chronic toxicity of palytoxin was evaluated after oral administration to mice by gavage during a 28-day period. After chronic exposure of mice to the toxin, a lethal dose 50 (LD50) of 0.44 µg/kg of PLTX and a No-Observed-Adverse-Effect Level (NOAEL) of 0.03 µg/kg for repeated daily oral administration of PLTX were determined. These results indicate a much higher chronic toxicity of PLTX and a lower NOAEL than that previously described in shorter treatment periods, pointing out the need to further reevaluate the levels of this compound in marine products.


Processes ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1294
Author(s):  
Samuel Álvarez-Almazán ◽  
Gabriel Navarrete-Vázquez ◽  
Itzia Irene Padilla-Martínez ◽  
José Correa-Basurto ◽  
Diana Alemán-González-Duhart ◽  
...  

By activating PPAR-γ, thiazolidinediones normalize glucose levels in animal models of type 2 diabetes and in patients with this pathology. The aim of the present study was to analyze 219 new derivatives in silico and select the best for synthesis, to be evaluated for acute oral toxicity in female rats and for control of diabetes-related parameters in a rat model of streptozotocin-induced diabetes. The best compound was chosen based on pharmacokinetic, pharmacodynamic, and toxicological parameters obtained in silico and binding orientation observed by docking simulations on PPAR-γ. Compound 1G was synthesized by a quick and easy Knoevenagel condensation. Acute oral toxicity was found at a dose greater than 2000 mg/Kg. Compound 1G apparently produces therapeutic effects similar to those of pioglitazone, decreasing glycaemia and triglyceride levels in diabetic animals, without liver damage. Moreover, it did not cause a significant weight gain and tended to reduce polydipsia and polyphagia, while diminishing systemic inflammation related to TNF-α and IL-6. It lowered the level of endogenous antioxidant molecules such as reduced glutathione and glutathione reductase. In conclusion, 1G may be a candidate for further testing as an euglycemic agent capable of preventing the complications of diabetes.


Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1718
Author(s):  
Kaimin Lu ◽  
Jing Zhou ◽  
Jie Deng ◽  
Yangjun Li ◽  
Chuanfang Wu ◽  
...  

The incidence and prevalence of inflammatory bowel disorders (IBD) are increasing around the world due to bacterial infection, abnormal immune response, etc. The conventional medicines for IBD treatment possess serious side effects. Periplaneta americana (P. americana), a traditional Chinese medicine, has been used to treat arthritis, fever, aches, inflammation, and other diseases. This study aimed to evaluate the anti-inflammatory effects of oligosaccharides from P. Americana (OPA) and its possible mechanisms in vivo. OPA were purified and biochemical characterization was analyzed by HPGPC, HPLC, FT-IR, and GC–MS. Acute colitis mice model was established, the acute toxicity and anti-inflammatory activity were tested in vivo. The results showed OPA with molecular mass of 1.0 kDa were composed of 83% glucose, 6% galactose, 11% xylose, and the backbone was (1→4)-Glcp. OPA had potent antioxidant activities in vitro and significantly alleviated the clinical symptoms of colitis, relieved colon damage without toxic side effects in vivo. OPA exhibited anti-inflammatory activity by regulating Th1/Th2, reducing oxidative stress, preserving intestinal barrier integrity, and inhibiting TLR4/MAPK/NF-κB pathway. Moreover, OPA protected gut by increasing microbial diversity and beneficial bacteria, and reducing pathogenic bacteria in feces. OPA might be the candidate of complementary and alternative medicines of IBD with low-cost and high safety.


Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1860
Author(s):  
Patricia Diez-Echave ◽  
Izaskun Martín-Cabrejas ◽  
José Garrido-Mesa ◽  
Susana Langa ◽  
Teresa Vezza ◽  
...  

Limosilactobacillus reuteri INIA P572 is a strain able to produce the antimicrobial compound reuterin in dairy products, exhibiting a protective effect against some food-borne pathogens. In this study, we investigated some probiotic properties of this strain such as resistance to gastrointestinal passage or to colonic conditions, reuterin production in a colonic environment, and immunomodulatory activity, using different in vitro and in vivo models. The results showed a high resistance of this strain to gastrointestinal conditions, as well as capacity to grow and produce reuterin in a human colonic model. Although the in vitro assays using the RAW 264.7 macrophage cell line did not demonstrate direct immunomodulatory properties, the in vivo assays using a Dextran Sulphate Sodium (DSS)-induced colitic mice model showed clear immunomodulatory and protective effects of this strain.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Earnest Oghenesuvwe Erhirhie ◽  
Chidozie Ikegbune ◽  
Anthony Ifeanyi Okeke ◽  
Chukwunonso Chukwudike Onwuzuligbo ◽  
Ngozi Ukamaka Madubuogwu ◽  
...  

AbstractDevelopment of resistance by malaria parasites to conventional antimalarial drugs has rejuvenated the exploration of herbal medicine as alternatives. Also, the increasing rate of the use of herbal antimalarial remedies in combination with conventional antimalarial drugs (both synthetic and semi-synthetic) has inspired researchers to validate their herb-drug interaction effects. This review evaluated the interaction outcomes between herbal antimalarial drugs in combination with conventional antimalarial drugs. With the aid of electronic databases, Pubmed and Google scholar, articles related to this subject were sourced from English peer reviewed scientific journals published from 2003 to 2020. Search terms used include “antimalarial-herbal drugs interaction”, “antimalarial medicinal plant interactions with conventional antimalarial drugs”, “drug-herbal interactions, “antimalarial drugs and medicinal plants”. Synergistic, antagonistic and none effects were reported among 30 studies reviewed. Among 18 in vivo studies on P. berghei and P. yoelii nigerense infected mice model, 14 showed synergism, 3 showed antagonism and 1 involving three plants showed both effects. Among 9 in-vivo studies involving normal animal (non-infected), 2 showed antagonism, 2 showed synergism and 5 showed none-effects. Two (2) studies on human volunteers and one (1) in vitro quantitative study showed that Garcinia kola reduced plasma concentrations of quinine and halofantrine. Generally, majority of herbal antimalarial drugs showed synergistic effects with CAMDs. Vernonia amygdalina was the most studied plant compared to others. Consequently, herbal remedies that produced synergistic effects with conventional antimalarial drugs may be prospects for standardization and development of antimalarial-medicinal plant combination therapy that could curtail malaria resistance to conventional antimalarial therapies.


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