Oral toxicity evaluation of probiotic strains isolated from Finger millet [Eleusine coracana (L.) Gaertn.] in Wistar rat models (in vivo)

This study evaluates the oral toxicity of five probiotic strains recently isolated from fermented flour of finger-millet (Eleusine coracana) varieties of Sri Lanka. Probiotic strains; Lactobacillus plantarum MF405176, Lactobacillus fermentum MF033346, Lactococcus lactis subspecies lactis MF480428, Enterococcus faecium MF480431and Pediococcus acidilactici MF480434 were evaluated for acute and sub-chronic oral toxicity in Wistars. Three individual doses (108 CFU/g, 1010 CFU/g and 1012 CFU/g) of each probiotic strain at single oral dose of 5000 mg/kg bw were orally administered to rats and observations were done till 14th day. Since no animals demonstrated signs of toxicity as a result of the administrated probiotics strains, repeated dose sub-chronic oral toxicity study was conducted by oral administration of three doses (108 CFU/g, 1010 CFU/g, 1012 CFU/g) of each probiotic strain at 1000 mg/kg bw/day for consecutive 90 days. Administration of probiotic strains to rats did not caused mortality in any of the tested doses. No changes in animal behavior, feed or water intake and negative effects on body weight observed. Probiotic feeding did not cause changes in analyzed biochemical and hematological parameters attributed to toxicity. Bacteremia, bacterial translocation and histopathological changes in rat organs were not observed. No significant difference in liver enzymes observed in treatment groups compared to control. In conclusion, all tested probiotic strains are nonpathogenic therefore could be considered as safe for human consumption.

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Extruded breakfast meal from malted finger millet (Eleusine coracana) and watermelon (Citrullus lanatus) seed flour: in-vivo nutritional qualities study

Bulletin of the National Research Centre ◽

10.1186/s42269-021-00533-x ◽

2021 ◽

Vol 45 (1) ◽

Author(s):

Joseph Oghenewogaga Owheruo ◽

Timilehin David Oluwajuyitan ◽

Beatrice Olawunmi Ifesan ◽

Matthew Kolawole Bolade

Keyword(s):

Finger Millet ◽

Citrullus Lanatus ◽

Breakfast Meal ◽

Formulated Diets ◽

Cell Counts ◽

Formulated Diet ◽

Significant Difference ◽

Nutritional Qualities ◽

Flour Blends

Abstract Background The study aimed at evaluating the in-vivo nutritional qualities of extruded breakfast meal produced from flour blends of malted finger millet and watermelon seed. Results The proximate compositions of the flour blends revealed that there was progressive increase in protein (12.83–15.14) %, with increase in the watermelon substitution. The protein quality evaluation of the extrudate showed that the protein efficiency ratio ranged from 0.64 to 89.75, while the biological values were between (87.82–89.75)%. The relative organs weight of rats fed with extruded breakfast meal showed that, the weights of the kidney and liver of rats fed with extruded breakfast meal were significantly lower compared with rats fed with goldenmorn. The hematological indices showed that the packed cell volume and the red blood cell counts of rats fed with the formulated diets were significantly lower compared with those fed with goldenmorn but significantly higher than rats fed with basal. Meanwhile, the values of the white blood cells count for the formulated diet shows no significant difference compared with rats fed with goldenmorn. Conclusions Evidently, the growth performance of the rats fed with the extruded breakfast meal revealed that the formulated diets promote growth status of the animals with relatively low effect on organs of experimental rat used in this study. Hence, formulated diet may serve as alternative to expensive commercial breakfast meal.

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In-vivo Antiplasmodial Effect of Dihydroartemisinin-Piperaquine-Nitrofurantoin on Plasmodium berghei- Infected Mice

Journal of Advances in Medical and Pharmaceutical Sciences ◽

10.9734/jamps/2021/v23i930256 ◽

2021 ◽

pp. 12-20

Author(s):

Udeme O. Georgewill ◽

Festus Azibanigha Joseph ◽

Elias Adikwu

Keyword(s):

Plasmodium Berghei ◽

Blood Cells ◽

Hematological Parameters ◽

White Blood Cells ◽

Positive Control ◽

Negative Control ◽

Antiplasmodial Activity ◽

Significant Difference ◽

Tract Infections

Nitrofurantoin (NT) used for the treatment of urinary tract infections may have antiplasmodial activity. Dihydroartemisinin-piperaquine (DP) is an artemisinin based combination therapy used for the treatment of malaria. This study evaluated the antiplasmodial effect of dihydroartemisinin-piperaquine-nitrofurantoin (DP-NT) on mice infected with Plasmodium berghei. Adult Swiss albino mice (30-35 g) of both sexes were used. The mice were randomly grouped, inoculated with Plasmodium berghei, and treated orally with DP (1.7/13.7 mg/kg), NT (57.1 mg/kg) and DP-NT (1.71/13.7/ 57.1 mg/kg), respectively using curative, prophylactic and suppressive tests. The negative control was orally treated with normal saline (0.3 mL), while the positive control was orally treated with chloroquine CQ (10mg/kg). After treatment, blood samples were collected and evaluated for percentage parasitemia, inhibitions and hematological parameters. Liver samples were evaluated for histological changes. The mice were observed for mean survival time (MST). Treatment with DP-NT decreased parasitemia levels when compared to individual doses of DP and NT with significant difference observed at p<0.05. DP-NT prolonged MST when compared to individual doses of DP and NT with significant difference observed at p<0.05. The decrease in packed cell volume, red blood cells, hemoglobin and increase in white blood cells in parasitized mice were significantly restored by DP-NT when compared to individual doses of DP and NT with difference observed at p<0.05. DP-NT eradicated liver Plasmodium parasite. NT remarkably increased the antiplasmodial activity of DP. DP-NT may be used for the treatment of malaria.

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

Journal of Toxicology ◽

10.1155/2021/5570206 ◽

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.

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Toxicological Evaluation of a Mixture of Astragalus membranaceus and Panax notoginseng Root Extracts (InnoSlim®)

Journal of Toxicology ◽

10.1155/2019/5723851 ◽

2019 ◽

Vol 2019 ◽

pp. 1-14 ◽

Cited By ~ 1

Author(s):

Timothy S. Murbach ◽

Róbert Glávits ◽

John R. Endres ◽

Gábor Hirka ◽

Adél Vértesi ◽

...

Keyword(s):

Micronucleus Test ◽

Panax Notoginseng ◽

Astragalus Membranaceus ◽

Human Consumption ◽

Oral Toxicity ◽

Toxicological Evaluation ◽

Root Extracts ◽

Dose Oral ◽

History Of

Astragalus spp. and Panax spp. have a long history of traditional human use. A blend, InnoSlim®, of highly purified and fractionated root extracts from Astragalus membranaceus and Panax notoginseng has now been developed for human consumption; however, the unique constituent content of this blend has not been specifically evaluated with respect to safety. Therefore, the toxicological potential of the blend was formally investigated in a series of studies—genetic toxicity was evaluated in a bacterial reverse mutation test followed by an in vivo mammalian micronucleus test, and general toxicity was evaluated in a 28-day repeated-dose oral toxicity study in rats. No evidence of mutagenicity was observed in the bacterial tester strains used, and no evidence of in vivo chromosomal damage resulting in increased frequency of micronucleated cells was observed in male Crl:NMRI BR mice. No mortality or toxic effects were observed, and no target organs were identified, in male and female Han:WIST rats exposed to 0, 400, 800, or 1200 mg/kg bw/day of the blend by gavage for 28 consecutive days. The highest dose—1200 mg/kg bw/day—was determined to be the NOAEL. Based on these results, extrapolation towards a safe human consumption level can be explored.

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Manufacturing process influences properties of probiotic bacteria

British Journal Of Nutrition ◽

10.1017/s0007114510004496 ◽

2010 ◽

Vol 105 (6) ◽

pp. 887-894 ◽

Cited By ~ 78

Author(s):

Łukasz Grześkowiak ◽

Erika Isolauri ◽

Seppo Salminen ◽

Miguel Gueimonde

Keyword(s):

Human Subjects ◽

Lactobacillus Rhamnosus ◽

Clinical Intervention ◽

Probiotic Strain ◽

Adhesion Properties ◽

Influence Model ◽

Intestinal Mucus ◽

Probiotic Strains ◽

Micro Organisms

Production and manufacturing methods and the food carrier may influence the properties of probiotic strains, and have an impact on the outcome of clinical intervention studies. The aim of the present study was to establish whether the properties of a specific probiotic strain,Lactobacillus rhamnosusGG, may differ depending on the product and source of the strain. In total, fifteen differentL. rhamnosusisolates, among them fourteen labelled asL.rhamnosusGG, were isolated from specific probiotic products. The micro-organisms were phenotypically and genotypically characterised. Their adhesion properties were compared using the human intestinal mucus model, and the ability of the isolates to influence model pathogen adhesion to human colonic mucus was assessed. AllL. rhamnosusisolates used were confirmed as members of the speciesL. rhamnosus. Except the reference strain OL, allL.rhamnosusisolates showed randomly amplified polymorphic DNA, enterobacterial repetitive intergenic consensus and pulsed-field gel electrophoresis profiles identical to that ofL. rhamnosusGG (ATCC 53103). AllL.rhamnosusisolates showed similar tolerance to acid and were able to bind to human colonic mucus. However, pathogen exclusion by inhibition and competition varied significantly among the differentL. rhamnosusisolates and pathogens tested. The results suggest that different sources of the same probiotic may have significantly altered strain properties. This should be considered inin vivostudies on human subjects and also for quality control of probiotic products.

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Acute and Subchronic Toxicity Study ofEuphorbia hirtaL. Methanol Extract in Rats

BioMed Research International ◽

10.1155/2013/182064 ◽

2013 ◽

Vol 2013 ◽

pp. 1-14 ◽

Cited By ~ 31

Author(s):

Kwan Yuet Ping ◽

Ibrahim Darah ◽

Yeng Chen ◽

Subramaniam Sreeramanan ◽

Sreenivasan Sasidharan

Keyword(s):

Body Weight ◽

Toxicity Study ◽

Morphological Alteration ◽

Control Group ◽

Sprague Dawley ◽

Oral Toxicity ◽

Methanolic Extracts ◽

Sprague Dawley Rats ◽

Significant Difference

DespiteEuphorbia hirtaL. ethnomedicinal benefits, very few studies have described the potential toxicity. The aim of the present study was to evaluate thein vivotoxicity of methanolic extracts ofE. hirta. The acute and subchronic oral toxicity ofE. hirtawas evaluated in Sprague Dawley rats. The extract at a single dose of 5000 mg/kg did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 14-day observation period. Therefore, the LD 50 of this plant was estimated to be more than 5000 mg/kg. In the repeated dose 90-day oral toxicity study, the administration of 50 mg/kg, 250 mg/kg, and 1000 mg/kg/day ofE. hirtaextract per body weight revealed no significant difference (P>0.05) in food and water consumptions, body weight change, haematological and biochemical parameters, relative organ weights, and gross findings compared to the control group. Macropathology and histopathology examinations of all organs including the liver did not reveal morphological alteration. Analyses of these results with the information of signs, behaviour, and health monitoring could lead to the conclusion that the long-term oral administration ofE. hirtaextract for 90 days does not cause sub-chronic toxicity.

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Safety Evaluation of Bifidobacterium lactis BL-99 and Lacticaseibacillus paracasei K56 and ET-22 in vitro and in vivo

Frontiers in Microbiology ◽

10.3389/fmicb.2021.686541 ◽

2021 ◽

Vol 12 ◽

Author(s):

Hongyun Lu ◽

Wen Zhao ◽

Wei-Hsien Liu ◽

Ting Sun ◽

Hanghang Lou ◽

...

Keyword(s):

Safety Evaluation ◽

Toxicity Tests ◽

Human Consumption ◽

Oral Toxicity ◽

Bifidobacterium Lactis ◽

Consumer Concerns ◽

Healthy Diets ◽

Dose Dependent

Probiotics have been reported to play a major role in maintaining the balance of microbiota in host. Consumption of food with probiotics has increased with consumer concerns regarding healthy diets and wellness. Correspondingly, safety evaluation of probiotics for human consumption has become increasingly important in food industry. Herein, we aimed to test the safety of Bifidobacterium lactis BL-99 and Lacticaseibacillus paracasei K56 and ET-22 strains in vitro and in vivo. In results, these strains were found to be negative for mucin degradation and platelet aggregation test. Additionally, the three strains were susceptible to eight antibiotics. In accordance with bacterial reversion mutation (Ames) assay, the tested strains had no genetic mutagenicity. Finally, it was confirmed that there were no dose-dependent mortality and toxicity throughout multidose oral toxicity tests in rats. Our findings demonstrated that B. lactis BL-99 and L. paracasei K56 and ET-22 can achieve the generally recognized as safe (GRAS) status as probiotics in the future.

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Absence of Mutagenicity, Genotoxicity, and Subchronic Oral Toxicity of Touchi Extract

International Journal of Toxicology ◽

10.1080/10915810701620374 ◽

2007 ◽

Vol 26 (5) ◽

pp. 465-473 ◽

Cited By ~ 4

Author(s):

Hiroyuki Fujita ◽

Tomohide Yamagami

Keyword(s):

Micronucleus Test ◽

Clinical Signs ◽

Water Extract ◽

Human Consumption ◽

Mouse Bone Marrow ◽

Oral Toxicity ◽

Subchronic Toxicity ◽

Toxicological Studies ◽

Chinese Food

Touchi, a traditional Chinese food used mainly for seasoning is obtained by first steaming soybeans followed by fermentation with Aspergillus oryzae (koji). A series of toxicological studies was conducted to evaluate the mutagenic and genotoxic potential and subchronic toxicity of a water extract of Touchi, a known inhibitor of α-glucosidase activity. Touchi extract (TE) did not induce reverse mutations in Salmonella typhimurium strains TA98, TA1537, TA100, TA1535, and Escherichia coli WP2uvrA at concentrations up to 5000 μg/plate, in either the absence or presence of exogenous metabolic activation. No deaths occurred and no abnormal clinical signs were observed in any animal in any group in an in vivo micronucleus test, and TE was devoid of clastogenic activity when administered orally to mice at doses up to 2000 mg/kg/day. Thus, TE was evaluated as negative in the bacterial reverse mutation and mouse bone marrow micronucleus tests under the conditions of these assays. To evaluate its subchronic toxicity, SPF rats were administered TE at doses of 0,250,1000, and 2500 mg/kg/day via oral gastric intubation. No treatment-related toxic changes were seen in clinical signs, body weight, food consumption, urinalysis, hematology, blood chemistry, necropsy, organ weight, or histopathology. The no observed adverse effect level for TE was thus considered to be more than 2500 mg/kg/day in both males and females. These results are consistent with Touchi’s status as a traditional Chinese food derived from fermented soybeans and its purported long history of use. Specifically, these data are consistent with the expected safety of human consumption of TE up to at least 5 g/day.

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Safety Assessment of Acer tegmentosum Maxim. Water Extract: General Toxicity Studies in Sprague–Dawley Rats and Beagle Dogs With Re-evaluation of Genotoxic Potentials

Frontiers in Pharmacology ◽

10.3389/fphar.2021.687261 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jin-Sung Park ◽

Euna Kwon ◽

Yun-Soon Kim ◽

Sang-Moo Kim ◽

Dae-Sun Kim ◽

...

Keyword(s):

Acute Toxicity ◽

Clinical Signs ◽

Water Extract ◽

Deciduous Tree ◽

Human Consumption ◽

Beagle Dogs ◽

Sprague Dawley ◽

Oral Toxicity

Acer tegmentosum Maxim., commonly known as Manchurian stripe maple, is a deciduous tree belonging to the family of Aceraceae and has been traditionally used in folk medicine for its remedial effects in liver diseases and traumatic bleedings. With a growing body of experimental evidence for its pharmacological efficacies, such as neuroprotective, hepatoprotective, antioxidant, and anti-inflammatory activities, A. tegmentosum has gradually gained popularity as a health supplement and functional food. However, the large part of essential toxicity information still remained lacking despite the possibility of mutagenic potentials as previously suggested, posing safety concerns for human consumption. In this study, we evaluated 90-day repeated oral toxicity of A. tegmentosum Maxim. water extract (ATWE) in SD rats with acute toxicity assessment in beagle dogs, and reevaluated genotoxicity using a combination of in vitro and in vivo assays. During the oral study period, ATWE did not cause toxicity-related clinical signs and mortality in rodents without adverse effects observed in the analysis of hematology, serum biochemistry, and histopathology, establishing >5,000 mg/kg BW as the NOAEL. In addition, doses up to 5,000 mg/kg BW did not cause acute toxicity in beagle dogs. When assessed for genotoxicity using bacterial reverse mutation, chromosome aberration, and micronucleus formation, ATWE showed lack of mutagenicity and clastogenicity. These results demonstrated that AWTE was safe in the present preclinical study for systemic toxicity and genotoxicity at the tested doses, providing a guideline for safe use in humans.

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Bacteriocin production as a mechanism for the antiinfective activity of Lactobacillus salivarius UCC118

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0700440104 ◽

2007 ◽

Vol 104 (18) ◽

pp. 7617-7621 ◽

Cited By ~ 497

Author(s):

Sinéad C. Corr ◽

Yin Li ◽

Christian U. Riedel ◽

Paul W. O'Toole ◽

Colin Hill ◽

...

Keyword(s):

Foodborne Pathogen ◽

Antimicrobial Effect ◽

Probiotic Strain ◽

Bacteriocin Production ◽

Human Origin ◽

Lactobacillus Salivarius ◽

Immunity Protein ◽

Probiotic Strains ◽

Stable Mutant

The mechanisms by which probiotic strains enhance the health of the host remain largely uncharacterized. Here we demonstrate that Lactobacillus salivarius UCC118, a recently sequenced and genetically tractable probiotic strain of human origin, produces a bacteriocin in vivo that can significantly protect mice against infection with the invasive foodborne pathogen Listeria monocytogenes. A stable mutant of Lb. salivarius UCC118 that is unable to produce the Abp118 bacteriocin also failed to protect mice against infection with two strains of L. monocytogenes, EGDe and LO28, confirming that bacteriocin production is the primary mediator of protection against this organism. Furthermore, Lb. salivarius UCC118 did not offer any protection when mice were infected with a strain of L. monocytogenes expressing the cognate Abp118 immunity protein AbpIM, confirming that the antimicrobial effect is a result of direct antagonism between Lb. salivarius and the pathogen, mediated by the bacteriocin Abp118.

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