Evaluation of the Genotoxic Potential againstH2O2-Radical-Mediated DNA Damage and Acute Oral Toxicity of Standardized Extract ofPolyalthia longifoliaLeaf

Medicinal plants have been used in medicoculturally diverse countries around the world, where it is a part of a time-honoured tradition that is respected even today.Polyalthia longifolialeaf extract has been previously reported as an efficient antioxidantin vitro. Hence, the genotoxic effects ofP. longifolialeaf were investigated by using plasmid relation, comet, andAllium cepaassay. In the presence of ∙OH radicals, the DNA in supercoil was start nicked into open circular form, which is the product of the single-stranded cleavage of supercoil DNA and quantified as fragmented separate bands on agarose gel in plasmid relation assay. In the plasmid relation and comet assay, theP. longifolialeaf extract exhibited strong inhibitory effects against H2O2-mediated DNA damage. A dose-dependent increase of chromosome aberrations was also observed in theAllium cepaassay. The abnormalities scored were stickiness, c-mitosis, bridges, and vagrant chromosomes. Micronucleated cells were also observed at the interphase. The results ofAllium cepaassay confirmed that the methanol extracts ofP. longifoliaexerted no significant genotoxic or mitodepressive effects at 100 μg/mL. Thus, this study demonstrated thatP. longifolialeaf extract has a beneficial effect against oxidative DNA damage. This experiment is the first report for the protective effect ofP. longifoliaon DNA damage-induced by hydroxyl radicals. Additionally in acute oral toxicity study, female rats were treated at 5000 mg/kg body weight ofP. longifolialeaf extract and observed for signs of toxicity for 14 days.P. longifolialeaf extract did not produce any treatment-related toxic effects in rats.

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Acute and sub-acute oral toxicity of aqueous whole leaf and green rind extracts of Aloe vera in Wistar rats

BMC Complementary Medicine and Therapies ◽

10.1186/s12906-021-03470-4 ◽

2022 ◽

Vol 22 (1) ◽

Author(s):

Florence Nalimu ◽

Joseph Oloro ◽

Emanuel L. Peter ◽

Patrick Engeu Ogwang

Keyword(s):

Toxicity Test ◽

Wistar Rats ◽

Leaf Extract ◽

Aloe Vera ◽

Female Rats ◽

Male Rats ◽

Aqueous Extracts ◽

Acute Oral Toxicity ◽

Oral Toxicity ◽

Leaf Extracts

Abstract Background Several local communities in Central, Western, Eastern, and Northern regions of Uganda have been using the whole leaf extracts of Aloe vera (L.) Burm. f. (Asphodelaceae) in the treatment of various ailments. Also, several commercial companies sell A. vera as soft drinks in Uganda. However, there are inadequate reports on the toxicities of such preparations. This paper reports the acute and sub-acute oral toxicity of aqueous extracts of whole leaf and green rind of A. vera in Wistar rats. Methods Acute oral toxicity test was carried out in female Wistar rats at doses of 175, 550, 1750, and 5000 mg/kg, p.o. The animals were observed for signs of toxicity for 14 days. Similarly, a sub-acute oral toxicity test was performed in both sexes of rats at doses of 200, 400, and 800 mg/kg, p.o. daily for 28 days. All the groups of animals were monitored for behavioral, morphological, biochemical, and physiological changes, including mortality and compared with respective controls. Body weights were measured weekly while the animals’ relative organ weights, hematological, biochemical, gross, and microscopic pathology were examined on day 29. Results There was no mortality or apparent behavioral changes at the doses tested in acute and sub-acute oral toxicity tests. Thus, the Median Lethal Dose (LD50) of green rind and whole leaf aqueous extracts was above 5000 mg/kg. Gross anatomy revealed that the rats’ relative spleen weight in green rind extract at 200 mg/kg significantly decreased compared to the control group. The creatinine levels in female rats that received green rind extract and the chloride ion levels in male rats administered whole leaf extract were significantly elevated. Conversely, Mean Corpuscular Hemoglobin Concentration (MCHC) levels significantly decreased at lower doses of the green rind extract compared to the control. Histopathology of the kidney revealed the renal interstitium’s inflammation at doses of 200 and 800 mg/kg of the whole leaf extract. Conclusion The findings demonstrated that A. vera green rind and whole leaf extracts are non-toxic at relatively high doses when used for a short duration. Prolonged use of the aqueous whole leaf extract might be associated with kidney toxicity.

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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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Phytochemical Study, Acute Toxicity and Fertility Potential Effect of Sarcocephalus latifolius (Smith) on the Histology of Wistar Rats Testicles

European Journal of Medicinal Plants ◽

10.9734/ejmp/2021/v32i230373 ◽

2021 ◽

pp. 62-69

Author(s):

Blahi Méa Adélaïde Nadia ◽

Affy Mataphouet Emmanuel ◽

Zougrou N’guessan Ernest ◽

Kouakou Koffi

Keyword(s):

Acute Toxicity ◽

Leaf Extract ◽

Female Rats ◽

Albino Rats ◽

Acute Oral Toxicity ◽

Oral Toxicity ◽

Phytochemical Study ◽

Aqueous Leaf Extract ◽

Fertility Potential ◽

Chemical Groups

Sarcocephalus latifolius is a popular medicinal plant used in treatment of many ailments basically in West Africa and particularly in Ivory Coast. Thereby, this study aims to find out the major chemical groups in the aqueous leaf extract of Sarcocephalus latifolius, its acute toxicity and its fertility potential. In this perspective, a phytochemical study to determine chemical groups was carried out. Furthermore, the acute oral toxicity study was conducted according to OECD guideline 423, using three female rats sequentially. As for the fertility study, it was performed on the histology of the testes of forty albino rats of 60 days of age weighing between 130 g and 170 g and treated for 30 and 60 days, at doses of 250; 500 and 1000 mg/kg body weight from the aqueous extract of Sarcocephalus latifolius. The phytochemical screaming of the aqueous leaf extract of Sarcocephalus latifolius revealed the presence of polyterpene sterols, polyphenols, flavonoids, quinonics and alkaloids. In addition, the acute oral toxicity assay did not reveal any signs of toxicity, morbidity or mortality at studied doses. Finally, the histology of testes of the albino rats treated with the plant extract showed a more intense spermatogenesis, seminiferous tubules and more developed interstitial tissue compared to control. To sum up Sarcocephalus latifolius, although rich in phytochemical compounds, might not be toxic in a single dose and might have androgenic effects.

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A Toxicological Evaluation of Mango Leaf Extract (Mangifera indica) Containing 60% Mangiferin

Journal of Toxicology ◽

10.1155/2019/4763015 ◽

2019 ◽

Vol 2019 ◽

pp. 1-14 ◽

Cited By ~ 12

Author(s):

Robin A. Reddeman ◽

Róbert Glávits ◽

John R. Endres ◽

Amy E. Clewell ◽

Gábor Hirka ◽

...

Keyword(s):

Leaf Extract ◽

Micronucleus Test ◽

Mangifera Indica ◽

Female Rats ◽

Oral Toxicity ◽

Toxicological Evaluation ◽

Male And Female Rats ◽

Toxicological Studies

A battery of OECD- and GLP-compliant toxicological studies was performed on mango leaf extract (Mangifera indica) containing 60% mangiferin (MLE). No evidence of genotoxicity was found in a bacterial reverse mutation test (Ames). While evidence of clastogenic activity was noted in an in vitro chromosomal aberration test, an in vivo mammalian micronucleus test showed no findings up to the limit dose (2000 mg/kg bw). A 90-day repeated dose oral toxicity study was conducted in rats using doses of 0 (vehicle control), 500, 1000, and 2000 mg/kg bw/day. Based on the lack of mortality or toxic effects in the 90-day study, the NOAEL for MLE in Han:Wist male and female rats was determined to be 2000 mg/kg bw/day, the highest dose tested.

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A New Symmetrical Thiazolidinedione Derivative: In Silico Design, Synthesis, and In Vivo Evaluation on a Streptozotocin- Induced Rat Model of Diabetes

Processes ◽

10.3390/pr9081294 ◽

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 ◽

...

Keyword(s):

Rat Model ◽

In Silico ◽

Female Rats ◽

Therapeutic Effects ◽

Acute Oral Toxicity ◽

Oral Toxicity ◽

In Vivo Evaluation ◽

Docking Simulations ◽

Ppar Γ

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.

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Beta-carotene enhances the recovery of lymphocytes from oxidative DNA damage.

Acta Biochimica Polonica ◽

10.18388/abp.1998_4300 ◽

1998 ◽

Vol 45 (1) ◽

pp. 183-190 ◽

Cited By ~ 21

Author(s):

L Fillion ◽

A Collins ◽

S Southon

Keyword(s):

Dna Damage ◽

Oxidative Damage ◽

Oxidative Dna Damage ◽

Enhanced Recovery ◽

Beta Carotene ◽

Epidemiological Studies ◽

Dietary Factors ◽

Causal Mechanism ◽

Strand Breaks

Epidemiological studies have revealed a strong correlation between high intake of fruit and vegetables and low incidence of certain cancers. Micronutrients present in these foods are thought to decrease free radical attack on DNA and hence protect against mutations that cause cancer, but the fine details of the causal mechanism have still to be elucidated. Whether dietary factors can modulate DNA repair--a crucial element in the avoidance of carcinogenesis--is an intriguing question that has not yet been satisfactorily answered. In order to investigate the effects of beta-carotene on oxidative damage and its repair, volunteers were given a single 45 mg dose and lymphocytes taken before and after the supplement were treated in vitro with H2O2. DNA strand breaks and oxidised pyrimidines were measured at intervals, to monitor the removal of oxidative DNA damage. We found inter-individual variations in response. In cases where the baseline plasma beta-carotene concentration was high, or where supplementation increased the plasma concentration, recovery from oxidative damage (i.e. removal of both oxidised pyrimidines and strand breaks) was relatively rapid. However, what seems to be an enhancement of repair might in fact represent an amelioration of the continuing oxidative stress encountered by the lymphocytes under in vitro culture conditions. We found that culture in a 5% oxygen atmosphere enhanced recovery of lymphocytes from H2O2 damage.

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In Vitro Studies on Pesticide-Induced Oxidative DNA Damage

Journal of the Turkish Chemical Society Section A Chemistry ◽

10.18596/jotcsa.67098 ◽

2016 ◽

Vol 3 (3) ◽

pp. 479

Author(s):

Özlem Demirci ◽

Bircan Çeken Toptancı ◽

Murat Kızıl

Keyword(s):

Dna Damage ◽

Oxidative Dna Damage ◽

In Vitro Studies

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Molecular Mechanisms of Zinc Oxide Nanoparticle-Induced Genotoxicity

Materials ◽

10.3390/ma10121427 ◽

2017 ◽

Vol 10 (12) ◽

pp. 1427 ◽

Cited By ~ 25

Author(s):

Agmal Scherzad ◽

Till Meyer ◽

Norbert Kleinsasser ◽

Stephan Hackenberg

Keyword(s):

Dna Damage ◽

Zinc Oxide ◽

Mammalian Cells ◽

Oxidative Dna Damage ◽

Molecular Mechanisms ◽

Consumer Products ◽

Zno Nps ◽

Cytotoxic Effects

Background: Zinc oxide nanoparticles (ZnO NPs) are among the most frequently applied nanomaterials in consumer products. Evidence exists regarding the cytotoxic effects of ZnO NPs in mammalian cells; however, knowledge about the potential genotoxicity of ZnO NPs is rare, and results presented in the current literature are inconsistent. Objectives: The aim of this review is to summarize the existing data regarding the DNA damage that ZnO NPs induce, and focus on the possible molecular mechanisms underlying genotoxic events. Methods: Electronic literature databases were systematically searched for studies that report on the genotoxicity of ZnO NPs. Results: Several methods and different endpoints demonstrate the genotoxic potential of ZnO NPs. Most publications describe in vitro assessments of the oxidative DNA damage triggered by dissoluted Zn2+ ions. Most genotoxicological investigations of ZnO NPs address acute exposure situations. Conclusion: Existing evidence indicates that ZnO NPs possibly have the potential to damage DNA. However, there is a lack of long-term exposure experiments that clarify the intracellular bioaccumulation of ZnO NPs and the possible mechanisms of DNA repair and cell survival.

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Induction of oxidative DNA damage and enhancement of cell proliferation in human lymphocytes in vitro by butylated hydroxyanisole

Carcinogenesis ◽

10.1093/carcin/16.3.507 ◽

1995 ◽

Vol 16 (3) ◽

pp. 507-512 ◽

Cited By ~ 15

Author(s):

P.A.E.L. Schilderman ◽

E. Rhijnsburger ◽

I. Zwingmann ◽

J.C.S. Kleinjans

Keyword(s):

Cell Proliferation ◽

Dna Damage ◽

Oxidative Dna Damage ◽

Human Lymphocytes ◽

Butylated Hydroxyanisole

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The Radiosensitizing Effect of Zinc Oxide Nanoparticles in Sub-Cytotoxic Dosing Is Associated with Oxidative Stress In Vitro

Materials ◽

10.3390/ma12244062 ◽

2019 ◽

Vol 12 (24) ◽

pp. 4062

Author(s):

Till Jasper Meyer ◽

Agmal Scherzad ◽

Helena Moratin ◽

Thomas Eckert Gehrke ◽

Julian Killisperger ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Zinc Oxide ◽

Zinc Oxide Nanoparticles ◽

Oxidative Dna Damage ◽

Clonogenic Survival ◽

Oxide Nanoparticles ◽

Radiosensitizing Effect ◽

Primary Fibroblasts

Radioresistance is an important cause of head and neck cancer therapy failure. Zinc oxide nanoparticles (ZnO-NP) mediate tumor-selective toxic effects. The aim of this study was to evaluate the potential for radiosensitization of ZnO-NP. The dose-dependent cytotoxicity of ZnO-NP20 nm and ZnO-NP100 nm was investigated in FaDu and primary fibroblasts (FB) by an MTT assay. The clonogenic survival assay was used to evaluate the effects of ZnO-NP alone and in combination with irradiation on FB and FaDu. A formamidopyrimidine-DNA glycosylase (FPG)-modified single-cell microgel electrophoresis (comet) assay was applied to detect oxidative DNA damage in FB as a function of ZnO-NP and irradiation exposure. A significantly increased cytotoxicity after FaDu exposure to ZnO-NP20 nm or ZnO-NP100 nm was observed in a concentration of 10 µg/mL or 1 µg/mL respectively in 30 µg/mL of ZnO-NP20 nm or 20 µg/mL of ZnO-NP100 nm in FB. The addition of 1, 5, or 10 µg/mL ZnO-NP20 nm or ZnO-NP100 nm significantly reduced the clonogenic survival of FaDu after irradiation. The sub-cytotoxic dosage of ZnO-NP100 nm increased the oxidative DNA damage compared to the irradiated control. This effect was not significant for ZnO-NP20 nm. ZnO-NP showed radiosensitizing properties in the sub-cytotoxic dosage. At least for the ZnO-NP100 nm, an increased level of oxidative stress is a possible mechanism of the radiosensitizing effect.

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