Background: Mentha mozaffarianii, an endemic species from the Labiatae family, is used in Iranian traditional medicine. This study evaluated the acute and repeated oral toxicity of the Mentha mozaffarianii essential oil (MMEO) in rats and mice. Methods: To assess the toxicity profile of the MMEO, we administered the essential oil to 48 rats and mice of both sexes by gavage in acute and repeated models. In acute toxicity, the animals were administered the MMEO (2000 mg/kg) and were monitored for 14 days. In the repeated toxicity, the MMEO was administered (100 mg/kg) daily for 4 weeks. On the 28th day, all the animals were scarified and blood and tissue samples were prepared. All the clinical, biochemical, and histopathological changes were assessed and compared with those in the controls. Statistical significance was determined by one-and two-way analyses of variance, followed by the Tukey test using GraphPad Prism 6. Results: In the acute test, there was no mortality; therefore, the oral LD50 value determined in the mice and rats of both sexes was greater than 2000 mg/kg. In the repeated test, the animals received the MMEO and there was no mortality. In the biochemical analysis, there were significant increases in blood glucose, cholesterol, ALT, AST, ALP, and TSH in the female rats and also in BUN in the male rats. The histopathological studies revealed evidence of microscopic lesions in the liver, kidney, stomach, and small intestine tissues of the MMEO group. Conclusion: The results indicated that the acute toxicity of the MMEO in the mice and rats was of a low order and it revealed slight tissue damage to several organs when given subchronically at a dose of 100 mg/kg.

Background: We aimed in this study to evaluate the acute and repeated dose toxicity of Kelussia odoratissima Mozaff (Kelussia) identified as a rare medicinal plant species which grows in western parts of Iran with potential nutraceutical applications. Materials and Methods: To determine the clinical, hematological, biochemical, necropsy and histopathological effects of the herb’ s essential oil, aerial parts of this plant were collected from Shahrekord in spring 2019. After careful evaluation and issuing the Herbarium Code Number, herb’ s dry powder was provided and the essential oil was prepared by Clevenger apparatus. Acute and repeated dose toxicity tests were performed by OECD 423 and 407 guidelines through intraperitoneal (i. p. ) injections to female rats. Results: Acute test didn’ t show any sign of toxicity in doses up to 2000 mg/kg and in delayed acute toxicity assessment no sign of toxic reaction was recorded. In repeated dose test all animals in two different dose groups (5 and 50 mg/kg) survived healthy according to the clinical, biochemical, hematological, necropsy and histopathological studies. Significant weight increase in high dose group (50 mg /kg/day) was accompanied with hepatotoxic reactions compared to vehicle control group (distilled water). Low dose group (5 mg/kg /day) showed significant biochemical changes in relevant nephrotoxicity related biomarkers which were not accompanied with histopathological evidence. Conclusion: The results of this study showed that oral long term administration of Kelussia essential oil could be considered as a safe herbal remedy in doses up to 5 mcg/kg/day for human medical and nutritional purposes.

Introduction: The genus Carduus belongs to Asteraceae family and is used to treat different human diseases, like cold, stomachache, and rheumatism. The current research investigated acute and repeated dose toxicity of Carduus pycnocephalus extract in mice. Materials and Methods: Acute and repeated-dose toxicity experiments were performed in female mice according to OECD 423 and 407 guidelines, respectively. Physical observations were made regularly and body weight was weekly measured. The organs weight, histopathology, and blood chemistry were then analyzed. Statistical analysis was done by the GraphPad Prism 8 software, and the results were presented as mean ±,SEM. P values below 0. 05 were considered significant. Results: No treatment-related mortalities were observed by oral administration of C. pycnocephalus extract up to the dose of 2000mg/kg. However, food consumption and water intake showed some variations in treated groups, and there were not any significant abnormalities related to treatment in treated groups in comparison to that in the control group in repeated-dose toxicity examination. Moreover, no significant alterations were noted in organ and body weight, food consumption, histopathology, and biochemical parameters in treated groups in comparison to the control group. Normal histological morphology was observed in all dose ranges and controls, except for the liver of high dose-treated samples which showed lymphocytic infiltrate and hepatocytes degeneration. Conclusion: LD50 of C. pycnocephalus extract could be above 2000mg/kg in acute toxicity experiment. Furthermore, with sub-chronical administration of the extract at a dose of 200 mg/kg, liver tissue was slightly damaged.

Background and objectives: Arctium lappa belonging to the Compositae (Asteraceae) family has been used as a medicinal and nutritional supplement in the world. The fruits, leaves and roots of the plant are well-known for their pharmaceutical effects. Toxicity of the fruit’ s extract in female rats was investigated in the present study. Methods: To assess the toxicity profile of Arctium lappa fruit extract (ALFE), it was administered to rats by gavage in acute and repeated models. The animals were divided into two groups: control and test groups. In the acute toxicity model, 1000 and 5000 mg/kg ALFE were administered to the animals. Toxic symptoms, body weight, death and abnormal behaviors were observed for 14 days. In the repeated toxicity model, ALFE (300 mg/kg) was daily administered for 4 weeks. Biochemical and histopathological changes were assessed and compared with the control group. Statistical significance was determined by one-way analyses of variance, followed by the Tukey test using GraphPad Prism 6. Results: No mortality was noticed in the acute test; therefore, the oral LD50 value determined in the female rats was greater than 5000 mg/kg. In the repeated test, the animals received ALFE (300 mg/kg) and no mortality was observed. The hematology and serum chemistry parameters showed no statistically significant changes. The histopathological studies revealed evidences of microscopic lesions in two main organs lungs and small intestine. Conclusion: The results indicated that the oral acute toxicity of ALFE in the rats was of a low order with LD50 being more than 5000 mg/kg. Moreover, they revealed slight tissue damage to several organs when sub-chronically administered at a dose of 300 mg/kg.

Iron oxide nanoparticles (IONPS) have different practical purposes in nanomedicine. These new applications of IONPS have raised risk of exposure of this nanomaterials to humans. Up to the present, all features of IONPS toxicity are not fully characterized after exposure to animals. The aim of the present study is to investigate the acute toxicity effects of IONPS in laboratory animals regarding pathotoxicological analysis and clinical aspects. Twenty four male Wistar rats were selected, and separated into four groups. The first, second, and the third groups received 50, 500, and 5000 mg/kg of IONPS solution orally for five days through gavage, respectively. Animal mortality, clinical sings and body weight were evaluated during the study. Fourteen days after the last administration, rats were euthanized for further investigation for histopathological evaluation. There were no death observed in all groups. High and middle dose of the IONPS caused symptoms like lethargy, ataxia, anorexia, isolation, and respiratory arrhythmia over the period of the study. The subjects of the low dose group showed no signs of toxicity. Specific histopathological complications, like hyaline cast in the kidneys, hyperemia and interstitial thickening in the lungs, hemorrhage in the heart and hepatic degeneration in the liver were observed in high dose group. Thus, it can be concluded that, toxicity of IONPS in rats is dose-dependent. This particular size of IONPS can induce serious pathological abnormalities and clinical symptoms in high dose.

Avicularin is a bioactive flavonoid that mainly found in blueberries, American cranberries, apples, and tea. Avicularin isolated from various plants including, Polygonum aviculare, Rhododendron aureum, and Taxillus kaempferi. Various preclinical studies already demonstrated antioxidant, anti-inflammatory, anti-depressant activity and neuroprotective action of avicularin. Furthermore, avicularin is a promising phytoconstituent with wide range of therapeutic potential in a variety of diseases. Hence, a toxicity study is urgently needed so that the appropriate dose can be used in animal studies to demonstrate its potential effect. The main aim of this research article is to find out maximum tolerated dose (MTD) and to observe if there’s any sign of toxicity in avicularin administered animals. Acute toxicity study was conducted as per OECD guideline (TG 423), a single dose of 300, 2000, 5000 mg/kg was given and the study was carried out for 14 days. In acute toxicity study, animals did not show any mortality or changes in behavioural pattern. Hence, it was concluded that, the maximum tolerated dose of avicularin is more than 5000 mg/kg. In a repeated-dose toxicity study, we have followed OECD guideline (TG 407) and rats were treated with 25, 50, and 100 mg/kg/day for 28 days. In Repeated toxicity study, animal showed no differences in hematologic and biochemical parameters. Histopathologic examination of all organs revealed normal histology. Hence, we can conclude from the findings that repeated avicularin exposure at 25, 50, and 100 mg/kg was determined to be safe in a 28-day toxicity study.

Objective(s): Quercus brantii galls (QBGs) are well-known in Iranian traditional medicine for treating various diseases. The aim of study was to assess the acute and repeated oral toxicity of the hydroalcoholic extract of QBG in female rats. Materials and Methods: The ethanolic extract of QBG was administered in rats by gavage in both acute and repeated dose models. In the acute section of the study, a single oral dose of 2000 mg/kg was administered to female rat which were observed for physical symptoms and behavioral changes for 14 days. In the repeated dose toxicity study, the QBG extract (50, 500, and 1000 mg/kg/day) was administered for a period of 28 days to rats. On 28th day of experiment, blood sampling of animals was done for hematological and biochemical analysis and then sacrificed for histopathological examination of the harvested tissues (liver, heart, kidney, lung, spleen, stomach, ovary and uterus). Results: A single oral administration of the QBG extract (2000 mg/kg) did not produce mortality or significant behavioral changes during 14 days of observation. In repeated oral toxicity models, the extract significantly increased (P<0. 05) the levels of mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), thyroid-stimulating hormone (TSH) and significantly decreased the levels of triiodothyronine (T3) and thyroxin (T4) in 500 and 1000 mg/kg dosage. The histopathological studies showed the absence of toxic effects of QBG (50 mg/kg dosage) and revealed evidence of microscopic lesions in the liver, kidney, stomach, heart, spleen, lung, uterus, and ovary in the 500-and 1000-mg/kg groups. Conclusion: The results indicate that the oral acute toxicity of QBG extract was of a low order with LD50 being more than 2000 mg/kg in rats. In addition, slight tissue damage was observed in some tissues in the 500 and 1000 mg/kg groups. It was found that prolonged use at higher doses i. e. 500 mg/kg/day of QBG extract should be avoided.