Oral Toxicological Studies ofPuerariaFlower Extract: Acute Toxicity Study in Mice and Subchronic Toxicity Study in Rats

The aim of this study was to investigate the acute and subchronic toxicity of a film formulation that combines κ-Carrageenan and konjac glucomannan for soft capsule application. For the acute toxicity study, a dose of 2000 mg/kg body weight (bw) of the film suspension was administered orally to rats. The animals were observed for toxic symptoms and mortality daily for 14 days. In a subchronic toxicity study, the film suspension, at doses of 10, 30 and 75 mg/kg bw for 28 days, were orally administered to rats. After 28 days, the rats were sacrificed for hematological, biochemical and histological examination. In the acute toxicity study, neither signs of toxicity nor death among the rats were observed for up to 14 days of the experimental period. The results of the subchronic toxicity study show that there were no significant changes observed in the hematology and organ histology. Some alterations to the relative organ weight and blood biochemistry were observed, but they were considered to be temporary effects and not an indication of toxic effects. The overall findings of this study indicate that the film formulation of κ-Carrageenan and konjac glucomannan is non-toxic up to a dose of 75 mg/kg bw, which could be considered a safe dose for soft capsule application.

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Safety assessment of subtilisin QK in rats

BMC Pharmacology and Toxicology ◽

10.1186/s40360-021-00506-w ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Shuai Xiao ◽

Dingbang Hu ◽

Ya Gao ◽

Yang Ai ◽

Sang Luo ◽

...

Keyword(s):

Acute Toxicity ◽

Adverse Effects ◽

Oral Dose ◽

Fibrinolytic Activity ◽

Toxicity Study ◽

Subchronic Toxicity ◽

Safety Pharmacology ◽

Sd Rats ◽

Acute Toxicity Study ◽

Safety Pharmacology Study

Abstract Background Subtilisin QK is a serine protease in the subtilisin family, and is fermented by Bacillus subtilis QK02. The fibrinolytic activity of subtilisin QK was measured by detecting low molecular weight degradation products using a spectrophotometric method developed by Japan Bio Science Laboratory Co., Ltd. Subtilisin QK powder can maintain its fibrinolytic activity for more than 24 months when it is stored at room temperature and protected from light. Our previous results showed that subtlisin QK directly degraded cross-linked fibrins in the fibrin plate assay and effectively inhibited thrombosis in the mouse thrombus model. The aim of this study was to determine the acute toxicity, potential subchronic toxicity, and safety pharmacology of subtilisin QK in Sprague–Dawley (SD) rats. Methods In the acute toxicity study, a single oral dose of 100,000 FU/kg was administered to 10 female and 10 male SD rats. In the 28-day subchronic toxicity, 60 female and 60 male SD rats were randomly assigned to four experimental groups (daily oral dose of 0, 2500, 7500 and 25,000 FU/kg). In the safety pharmacology study, 20 female and 20 male SD rats were randomly assigned to four experimental groups (single oral dose of 0, 500, 1500 and 5000 FU/kg). Results No death occurred and no adverse effects were observed in the acute toxicity study at a dose of 100,000 FU/kg. In the 28-day subchronic toxicity study, several hematological and blood biochemical parameters showed increases or decreases; however, due to the lack of a dose–response relationship, these differences were considered unrelated to treatment. In the safety pharmacology study, no adverse effects were observed on the central nervous of SD rats post-administration up to a dose of 5000 FU/kg subtilisin QK. Conclusion The results showed that oral consumption of subtilisin QK is of low toxicological concern. No adverse effects were observed at doses of 2500, 7500, and 25,000 FU/kg in the 28-day subchronic toxicity, and the no-observed-adverse-effect level (NOAEL) of subtilisin QK was 25,000 FU/kg.

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TOXICOLOGICAL EVALUATION OF AYURVEDIC FORMULATION: GOKSHURADI GUGGULU

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i9.19295 ◽

2017 ◽

Vol 10 (9) ◽

pp. 57

Author(s):

Gamit Kanan G ◽

Raval Manan A

Keyword(s):

Acute Toxicity ◽

Dose Level ◽

Hematological Parameters ◽

Toxicity Study ◽

Toxicological Evaluation ◽

Acute Toxicity Study ◽

Toxicological Studies ◽

Histopathological Studies

Objective: To evaluate toxicological studies of Ayurvedic formulation Gokshuradi Guggulu (GG) on male Wistar rats.Methods: Acute toxicity study was conducted as per the Organisation for Economic Co-operation and Development guidelines.Results: Results from the present study have elucidated that treatment with GS exerted no significant signs of toxicity at dose level 2000 mg/kg body wt. There was no mortality observed in all the groups. Behavioral, biochemical, and hematological parameters and histopathological studies were not significantly much altered as compared to control group.Conclusion: LD50 for GS was >2000 mg/kg. Thus, it is regarded as safe or non-toxic.

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Absence of Detectable Toxicity in Rats Fed Partially Hydrolyzed Guar Gum (K-13) for 13 Weeks

International Journal of Toxicology ◽

10.1080/109158197226928 ◽

1997 ◽

Vol 16 (6) ◽

pp. 611-623 ◽

Cited By ~ 5

Author(s):

Takatoshi Koujitani ◽

Hidetoshi Oishi ◽

Yuji Kubo ◽

Toshihiro Maeda ◽

Keiji Sekiya ◽

...

Keyword(s):

Acute Toxicity ◽

Guar Gum ◽

Toxicity Study ◽

Oral Toxicity ◽

Subchronic Toxicity ◽

Mutagenic Potential ◽

Reverse Mutation ◽

Acute Toxicity Study ◽

K 13 ◽

Partially Hydrolyzed Guar Gum

Toxicity studies were conducted to evaluate acute and subchronic oral toxicity and mutagenicity of partially hydrolyzed guar gum (K-13). In an acute toxicity study, mice and rats were treated with K-13 at a dose of 6000 mg/ kg. There were no deaths, so the LD50s were >6000 mg/ kg in both species. In a subchronic toxicity study, K-13 was given to rats as a dietary admixture at concentrations of 0.2. 1.0 and 5.0% for 13 weeks. There were no effects attributable to K-13 in any examinations. K-13 proved to have no mutagenic potential in a reverse mutation test using bacteria.

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CHEMICAL COMPOSITION OF ESSENTIAL OIL AND EVALUATION OF ACUTE AND SUB-ACUTE TOXICITY OF DOREMA AMMONIACUM D. DON. OLEO-GUM-RESIN IN RATS

African Journal of Traditional Complementary and Alternative Medicines ◽

10.21010/ajtcam.vi15.1.3 ◽

2017 ◽

Vol 15 (1) ◽

pp. 26

Author(s):

Azade Raeesdana ◽

Mohammad Hosein Farzaei ◽

Mohsen Amini ◽

Roja Rahimi

Keyword(s):

Chemical Composition ◽

Acute Toxicity ◽

Essential Oil ◽

Toxicity Study ◽

Control Group ◽

Histopathological Analysis ◽

Medicinal Uses ◽

Acute Toxicity Study ◽

Toxicological Studies ◽

Resin Solution

Background: Dorema Ammoniacum is a perennial herb which has been used in Persian Traditional Medicine for different indications, including gastrointestinal disorders and sciatica. Despite numerous medicinal uses, there is a lack of toxicological studies on Dorema Ammoniacum; therefore, the aim of the present study is to investigate its possible toxic effects as well as the determining chemical composition of its essential oil. Materials and Methods: Acute toxicity study was performed by administration of single increasing geometric doses of oleo-gum-resin solution (1250, 2500, and 5000 mg/kg) to Wistar rats. For sub-acute toxicity study, repeated doses of oleo-gum-resin solution (100, 200 and 500 mg/kg) were administered orally to rats for 4 weeks. At the end of the treatment, histopathological studies, hematological assessments, and biochemical parameters were performed. Results: GC-MS was performed to determine the chemical composition of the essential oil. Acute toxicity results demonstrated no mortality, and the Median Lethal Dose (LD50) was greater than 5000 mg/kg. Sub-acute treatment did not show any significant changes in biochemical and hematological parameters at any doses compared to the control group. Histopathological analysis of the organs revealed varying effects. At the level of the liver, vacuolar degeneration and mild inflammation at 200 and 500 mg/kg doses were observed. At the level of kidney, congestion of glomeruli and a widening of the urinary space at 500mg/kg were observed compared to the control group. The principle components of the essential oil were Cuperene (14.31%) and β-Funebrene (12.74%). Conclusion: The results suggest that the acute administration of the oleo-gum-resin of D. Ammoniacum is not accompanied with signs of toxicity; however, its administration over the long term might associate with renal toxicity and hepatotoxicity.

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PHARMACOGNOSTIC, ANTIOXIDANT AND ACUTE TOXICITY STUDY OF Ficus sycomorus (Linn) (Moraceae) ROOT AND STEM BARK

FUDMA Journal of Sciences ◽

10.33003/fjs-2020-0402-244 ◽

2020 ◽

Vol 4 (2) ◽

pp. 605-614

Author(s):

Murtala M. Namadina ◽

H. Haruna ◽

U. Sanusi

Keyword(s):

Acute Toxicity ◽

Radical Scavenging ◽

Stem Bark ◽

The Body ◽

Toxicity Study ◽

Bark Extract ◽

Root Extract ◽

Acute Toxicity Study ◽

Radical Scavenging Ability ◽

Phytochemical Components

Most of biochemical reactions in the body generates Reactive Oxygen Species (ROS), which are involved in the pathogenesis of oxidative stress-related disorders like diabetes, nephrotoxicity, cancer, cardiovascular disorders, inflammation and neurological disorders when they attack biochemical molecules like proteins, lipids and nucleic acid. Antioxidants are used to protect the cells or tissues against potential attack by ROS. Most medicinal plants possess a rich source of antioxidants such as flavonoids, phenols, tannins, alkaloids among others. These phytochemicals are currently pursued as an alternative and complimentary drug. In this study, phytochemical components, antioxidant and acute toxicity study of the methanol extract of stem bark and root of F. sycomorus were carried out using standard methods. Findings from this study revealed the presence of some diagnostic microscopical features such as calcium oxalate, starch, gum/mucilage, lignin, Aleurone grain, suberized/Cuticular cell wall and inulin but calcium carbonate was absent in stem bark but present in the powdered root. Quantitative physical constants include moisture contents (6.40% and 7.82%), ash value (7.20% and 9.30 %) in stem bark and root respectively. Carbohydrates, alkaloid, flavonoids, saponins, tannins, glycoside, steroid, triterpenes and phenols were present in all the extracts. They were found to exhibit potent 1,1,-diphenyl 2-picryl hydrazyl (DPPH) free scavenging activity. The DPPH radical scavenging ability of the extracts showed the following trend Ascorbic acid < stem bark extract˃ root extract. The LD50 of the methanolic stem bark and root extracts were found to be greater than 5000 mg /kg and is considered safe for use. Nonetheless, further

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In-vitro and in-vivo evaluation of antidiabetic activity of Withania coagulans extract

The Natural Products Journal ◽

10.2174/2210315509666190416155757 ◽

2019 ◽

Vol 09 ◽

Author(s):

Tejas Patel ◽

B.N. Suhagia

Keyword(s):

Blood Glucose ◽

Acute Toxicity ◽

Aqueous Extract ◽

Pancreatic Beta Cell ◽

Toxicity Study ◽

Acute Toxicity Study ◽

Withania Coagulans ◽

Study Results

Background: Diabetes mellitus is major issue to public health as its prevalence is rising day by day. Synthetic agents available for the diabetic treatment are expensive or produce undesirable side effect on chronic use and some of them are not suitable during pregnancy. Herbal medicines accepted widely due to side effects and low cost. Objective: The aim of present study was to evaluate the activity of Withania coagulans extract using In-vitro and In-vivo model. Methods: Different three types of Withania coagulans extract were prepared using aqueous (W1), Alcohol (W2) and hydro-alcoholic (50:50) mixture (W3). In-vitro Anti-diabetic activity of the all three extracts evaluated using RINm5F Pancreatic beta cells.Further, n-vivo anti-diabetic evaluation performed by administering 50 mg/kg (p.o) aqueous extract for 7 days in Streptozotocin (STZ)-induced mice. Body weight of the animals was also determined to perform acute toxicity study. Results: The results of in –vitro cell based study indicated that among all three extract, aqueous extract (W1) of Withania coagulans showed potential increase in inulin release. The EC50 of the W1 (249.6 µg/L) which is compared with standard (Glibenclamide) EC50. From the results of In-vitro study, W1 subjected for acute toxicity study and the acute toxicity study results indicated LD50 of 50mg/kg. Diabetic rats treated with W1 extract at oral dose of 50 mg/kg for 7 days showed 34.17% reduction in blood glucose in comparison to untreated diabetic (STZ-induced) rats. Blood glucose levels of Standard treated (Glibenclamide) and control untreated. Conclusion: In conclusion, results of pancreatic beta cell based study showed increase in insulin release by administration of extract. Further aqueous extract (W1) was potentially reduced blood glucose level in STZ induced diabetic mice.

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Safety Evaluation of Eucalyptus globulus Essential Oils through Acute and Sub-acute Toxicity and Skin Irritation in Mice and Rats

Current Chemical Biology ◽

10.2174/2212796814999200818095036 ◽

2020 ◽

Vol 14 (3) ◽

pp. 187-195

Author(s):

Berhan Mengiste ◽

Tizazu Zenebe ◽

Kassahun Dires ◽

Ermias Lulekal ◽

Awol Mekonnen ◽

...

Keyword(s):

Acute Toxicity ◽

Essential Oil ◽

Eucalyptus Globulus ◽

Biochemical Parameters ◽

Skin Irritation ◽

Toxicity Study ◽

Subacute Toxicity ◽

Acute Toxicity Study ◽

Limit Test ◽

Ointment Formulation

Background: The Eucalyptus globulus extractions have been used by the traditional healers to treat diseases in the study area. Our previous study revealed that the essential oil has antimicrobial and antifungal activity. This study determined phytochemical analysis, skin irritation, acute and subacute toxicity of Eucalyptus globulus essential oil in mice and rats. Methods: The phytochemicals were analyzed using GC-MS mass spectrometry. The acute toxicity study was determined at three dose levels of 1500 mg/kg, 1750mg/kg, and 2000 mg/kg. The essential oil limit test at a dose of 1000 mg/kg was administered to mice for 28 consecutive days for sub-acute toxicity study. The mice mortality, behavioral change, injury and other signs of illness were recorded once daily. Biochemical parameters were evaluated. Liver and kidney were analyzed for histopathological analyses. The 5% ointment formulation was applied to the rat skin to determine skin irritation effects. Results: The Eucalyptus globulus essential oil showed no effect on the mice at a dose of 1500mg/kg and below, but caused signs of toxicity and death at a dose of 1750mg/kg and above compared to the controls (p<0.05). The LD50 value was 1650 mg/kg. There was no significant difference (p > 0.05) in the body weights, gross abnormalities of the organs and biochemical parameters compared to the control at 1000 mg/kg subacute toxicity study. No histopathological changes were detected in the organs tested. The 5% ointment formulation did not show any abnormal skin reaction. Discussion: In the present study, the Eucalyptus globulus essential oil was comparable with other studies in terms of both chemical composition and its effects on sub-acute and topical application. Conclusion: This toxicity study demonstrated that Eucalyptus globulus essential oil is nontoxic at a relatively lower concentration.

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