scholarly journals Two-Week Repeated Oral Dose Toxicity Study of Mantidis Ootheca Water Extract in C57BL/6 Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
Hye-Sun Lim ◽  
Yun Soo Seo ◽  
Seung Mok Ryu ◽  
Byeong Cheol Moon ◽  
Goya Choi ◽  
...  

Background. Mantidis Ootheca (MO), described as the ootheca of Hierodula patellifera Serville, 1839, Tenodera angustipennis (Saussure, 1869), or Statilia maculate (Thunberg, 1784) in Korean Herbal Pharmacopoeia, is an important herbal material that has been traditionally used for treating several medical conditions including renal failure, spermatorrhea, and pediatric enuresis in Korea. Objective. The present study investigated the potential subacute toxicity of MO water extract during a 2-week repeated oral administration of doses of 0, 50, 150, or 450 mg/kg/day to C57BL/6 male mice by gavage. Methods. The following parameters were examined during the study period: mortality, clinical signs, body weight, hematology, serum biochemistry, gross findings, organ weight, and histopathology. All the mice were euthanized at the end of the treatment period. Results. No treatment-related changes in mortalities, clinical signs, body weight, gross finding, and organ weight change were detected after 14 days of oral MO extract administration. In addition, no meaningful MO extract treatment-related changes were observed in the hematological, serum biochemical, and histopathological parameters compared with the normal control group following treatment with doses of up to 450 mg/kg/day. Conclusion. Based on these findings, we concluded that treatment of mice with the water extract of MO did not result in significant toxicity and, therefore, it could be considered safe for further pharmacological studies.

2020 ◽  
Vol 44 (2) ◽  
pp. 103-112
Author(s):  
Hiewa O. Dyary

Brown truffle (Terfezia claveryi) is a wild fungi species collected and consumed by humans in Iraq, especially during the raining season, from February to April. However, the toxicological effects of this fungus have not been studied in humans. This study tested the subacute toxicity of brown truffle’s methanolic extract on a rat model. Daily oral doses of 200, 400, and 800 mg/kg were administered to adult Sprague-Dawley rat groups of both sexes for 14 days. There were no behavioral changes, no alterations in body weight, organ weight, and body weight gain (p>0.05) in the treated rats, compared to the untreated control group. The hematological and serum biochemical parameters did not show significant (p>0.05) differences from the control. Microscopic examinations of the brain, lungs, liver, spleen, kidney, and heart tissues revealed no pathological lesions in treated rats’ organs. These results imply that the administration of methanolic extract of T. claveryi to rats does not result in observable toxicity


2021 ◽  
Author(s):  
Yongchun Li ◽  
Hui Zhang ◽  
Shanshan Chen ◽  
Liutao Zhao ◽  
Jie Wu ◽  
...  

Abstract Qing Hao Gan Cao (QHGC), a Chinese medicinal formula containing Artemisia annua and Glycyrrhizae Radix et Rhizoma, has been used to treat sunstroke and as an antiviral agent for more than 800 years. It has not previously been subject to a toxicological safety evaluation in acute and subacute (28 days) studies. Therefore, the acute and subacute toxicity of an aqueous extract of QHGC were evaluated in vivo. For the QHGC preparation, the botanical raw materials were crushed into pieces and mixed in the ratio of 10:1 in distilled water for 12 h, then boiling three times for 2 h each time. The three decoctions were mixed and filtered, then spray-dried with hot air at 160°C for 30 min, and stored at room temperature. For the acute toxicity test, 72.0 g/kg of QHGC extract was administered by gavage to male and female mice. Body weight, general observations, and autopsy results were recorded. No mortality or toxicity signs were observed during the studies. For the subacute toxicity test, 4.0, 8.0, or 16.0 g/kg/day of QHGC extract was administered to rats for 28 days. General observations and mortality, body weight, biochemical and hematological parameters, organ weight, and pathological morphology were analyzed. The acute and subacute toxicity studies did not show significant changes in body weight, general observations, hematology and biochemical parameters, organ weight, and liver, spleen, stomach, duodenum, testis, ovary, lung, heart, and kidney histopathological analyses. The consumption of QHGC aqueous extract can be considered safe within the conditions of this study.


Toxins ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 531 ◽  
Author(s):  
Eliane Dallegrave ◽  
Eliane Taschetto ◽  
Mirna Bainy Leal ◽  
Flavia Techera Antunes ◽  
Marcus Gomez ◽  
...  

Phα1β, a purified peptide from the venom of the spider Phoneutria nigriventer, and its recombinant form CTK 01512-2 are voltage-dependent calcium channel (CaV) blockers of types N, R, P/Q, and L with a preference for type N. These peptides show analgesic action in different pain models in rats. The aim of this study was to evaluate the acute intrathecal toxicity of the native and recombinant Phα1β toxin in Wistar rats. Clinical signs, serum biochemistry, organ weight, and histopathological alterations were evaluated in male and/or female rats. Dyspnea was observed in males, hyporesponsiveness in females, and Straub tail and tremors in both genders. There were no significant differences in male organ weight, although significant differences in the female relative weight of the adrenal glands and spleen have been observed; these values are within the normal range. Serum biochemical data revealed a significant reduction within the physiological limits of species related to urea, ALT, AST, and FA. Hepatic and renal congestion were observed for toxin groups. In renal tissue, glomerular infiltrates were observed with increased glomerular space. These histological alterations were presented in focal areas and in mild degree. Therefore, Phα1β and CTK 01512-2 presented a good safety profile with transient toxicity clinical signals in doses higher than used to obtain the analgesic effect.


2018 ◽  
Vol 7 (5) ◽  
pp. 412-418
Author(s):  
Mohd Urooj ◽  
◽  
Mohammad Ahmed Khan ◽  
G. Thejaswini ◽  
Munawwar Husain Kazmi ◽  
...  

Jawarish Shahi (JS) is a compound polyherbal Unani pharmacopoeial formulation indicated for Khafqan (Palpitation), Nafkh-e-Shikam (Flatulence) and Waswas (Insanity; false perception and hallucinations). Jawarish Shahi contains herbs like Halela (Terminalia chebula), Amla (Emblica officinalis), Kishneez (Coriandrum sativum), Elaichi Khurd, (Elettaria cardamomum), and Bed Mushk (Salix caprea). The present study was carried out as per OECD 408 guidance to evaluate 90 days repeated oral dose toxicity in male and female Sprague Dawley rats. The study was performed at dose levels 1028 and 2000 mg/kg bw. No adverse effects were reported with respect to body weight, feed intake, behavior and clinical signs indicative of systemic toxicity. The expected growth pattern was observed in body weight and feed intake as compared to control group at both dose levels in male and female rats. There were few significant alterations with respect to hematology, and clinical biochemistry, however the results were within normal range thus considered toxicologically insignificant. The microscopic examination of different organ/tissue showed that no histopathological changes were observed. The findings of the study showed that No Observed Adverse Effect Level (NOAEL) for JS is greater than 2000 mg/kg body weight


2000 ◽  
Vol 19 (4) ◽  
pp. 257-264 ◽  
Author(s):  
B. M. Ryan ◽  
R. Henrich ◽  
R. I. Freudenthal

Fyrolflex resorcinolbis-diphenylphosphate (RDP) is a nonhalogenphosphate ester product that is widely used as a flame retardant for petrochemicalplastics and high-temperature lubricant additive applications. The potential developmental toxicity of RDP was evaluated in rabbits. Groups of 27 sperm-positive New Zealand white rabbits (Hazelton Research Products Inc., Denver, PA) were administered graded concentrations of 50, 200, or 1000 mg/kg/day of RDP in corn oil. A vehicle control group of equal size was administered corn oil alone. Rabbits were dosed daily (1.5 ml/kg) on gestationdays 6 to 28 and sacrificed on gestationday 29. The fetuses were removed by cesarean section and examined for gross external, visceral, cephalic, and skeletal anomalies. No treatment-related clinical signs of toxicity were observed. No treatment-related effects in maternal food consumption, body weight, body weight gain, or on uterus, liver, kidney, and spleen weights were detected. Fetal viability and body weight, as well as developmental end points were also unaffected by treatment. Accordingly, exposure of pregnant rabbits to doses ranging from 50 to 1000 mg/kg/day of RDP during the periods of major organogenesis and histogenesis did not result in any biologically significant toxic or teratogenic/developmental effect in the dams or fetuses.


1979 ◽  
Vol 91 (3) ◽  
pp. 553-563 ◽  
Author(s):  
H. K. Kley ◽  
H. G. Solbach ◽  
J. C. McKinnan ◽  
H. L. Krüskemper

ABSTRACT The concentration of sex hormones and their binding in the plasma were measured in male patients (20–40 years old), who weighed 140–170 % (I), 170–200 % (II) and > 200 % (III) of their ideal weight. Correlated to body weight, there is a reduction in the total concentration of testosterone, which, in the very obese patients, amounts to 41 % (in group I: 85 % in group II: 68 % P < 0.001) of that found in an age-matched healthy control group of subjects of "normal" body weight (90–115 % of the ideal body weight; n: 20). Androstenedione values show only a trend downwards (from 0.94 to 0.72 ng/ml plasma), while the oestrogen values increase significantly; oestrone increases by a factor of 1.09 (I), 1.43 (II; P < 0.001) and 1.69 (III; P < 0.001) and oestradiol by 1.13, 1.43 P < 0.001) and 1.76 (P < 0.001), respectively. Despite the fall in testosterone there are no clinical signs of hypogonadism, as SHBG (from 5.1 ± 0.8 in the controls to 2.4 ± 0.6 ×10−8 Mol/l in the very obese patients of group III) and the protein-bound fraction of testosterone also decrease. As a result the concentration of free testosterone remains constant (120 pg/ml), except in the very obese (93 pg/ml). Because of the different affinity of the binding proteins for testosterone and oestradiol the ratio of free oestradiol: free testosterone shifts less strongly in favour of the feminizing hormone (11.1 × 10−3 in group III as compared to 4.1 × 10−3 in the controls), than is suggested by the total hormone concentrations. A disturbance in the gonadal function of the pituitary gland or the testes is not present, since the concentration of LH is normal and the testicular response to HCG in very obese patients adequate (increase of testosterone by a factor of 3.11 as compared to 2.23 in the controls). The cause of the decrease in testosterone and SHBG is unknown, while the increase of plasma oestrogens is likely to be due to the increased conversion of androgens to oestrogens in the adipose tissue, which clearly plays an important role for plasma concentrations of sex hormones in obese patients.


2003 ◽  
Vol 22 (1) ◽  
pp. 9-23 ◽  
Author(s):  
Abdelwahab Omri ◽  
Brian J. Agnew ◽  
Girishchandra B. Patel

Archaeosomes, liposomes made from polar ether lipids of archaea, show promise for vaccine and drug delivery applications. The potential toxicity of intravenously (14,70, or 140 mg/kg/day for 5 consecutive days) and orally (gavaged at 55,275, or 550 mg/kg/day for 10 consecutive days) administered unilamellar archaeosomes, prepared from the total polar lipids (TPLs) extracted from several species of archaea, was assessed in female BALB/c mice. Liposomes prepared from an ester phospholipid composition were included for comparative purposes. Control groups of mice were administered 0.1 ml phosphate-buffered saline (PBS) by either route. Animals were monitored at least once daily for temperature, body weight, and clinical signs of adverse reactions. One day after the last dose, the mice were sacrificed. Blood was collected for selected biochemical/enzyme analyses, and the major organs (heart, lungs, liver, spleen, kidneys) were weighed and examined macroscopically. In addition, the spleens were examined histologically. At the two lower dosages of intravenously administered vesicles, there were no significant indications of toxicity, as compared with the PBS-administered control group. At the highest intravenous dose of 140 mg/kg/day, archaeosomes prepared from the TPL of the extreme halophiles, Halobacterium salinarum and Natronobacterium magadii, indicated potential toxicity, as evidenced by clinical signs (hyperactivity and/or piloerection), drop in body temperature, and loss in body weight. Spleens from mice administered some archaeosomes types, primarily at the highest intravenous dose tested, were enlarged, had increased organ weight, and microscopic examination revealed mild to moderate expansion of the red pulp with increased numbers of hematopoietic cells, but no changes in the white pulp. There were similar clinical signs at one or more of the higher oral doses of the ester liposomes and some of the archaeosome types; however, no other apparent toxicity was observed. Based on this limited mouse study. archaeosomes were generally well tolerated after intravenous or oral delivery at the dosages so indicated in this study.


2001 ◽  
Vol 20 (5) ◽  
pp. 297-305 ◽  
Author(s):  
Tomoo Kuge ◽  
Takashi Shibata ◽  
Michael S. Willett ◽  
Patricia Turck ◽  
Karl A. Traul

Seirogan, an herbal medicine containing wood creosote (tablets, 10.0% w/w), has been developed and marketed for almost a century in various countries for the control of acute diarrhea and treatment of associated symptoms, such as abdominal cramping. Wood creosote (CAS no. 8021–39–4) is a mixture of simple phenolic compounds, including guaiacol and creosol and related compounds, and is chemically distinct from, and should not be confused with, coal tar creosote, a known carcinogen. In the current study, the oncogenic potential of wood creosote was assessed in a 96/103-week oral gavage study in Sprague-Dawley rats. Groups of 60 rats/sex received wood creosote at dose levels of 20, 50, or 200 mg/kg body weight [bw]/day. An additional group of rats received the vehicle, 0.5% carboxymethylcellulose in deionized, distilled water, at the same dose volume as the treatment groups (10 ml/kg) and served as the controls. Treatment-related decreases in survival, body weight, and food consumption, as well as increased incidences of clinical signs that included rales, decreased activity, and salivation, were noted at 200 mg/kg bw/day when compared with the control group. There was an increased incidence of reddened and edematous lungs in rats from the 200 mg/kg bw/day group that died during the study. The lung findings were suggestive of test article aspiration during dose administration or agonal aspiration preceding and possibly resulting in death, especially because these observations were not seen in animals that survived to scheduled sacrifice. Additionally, phenols are generally recognized as having corrosive properties. There were no changes in clinical pathology and no increases in neoplastic or non-neoplastic lesions, excluding the lung findings, related to treatment with wood creosote at any dose level. Although the results of this study indicate that the maximum tolerated dose of wood creosote was met or exceeded at 200 mg/kg bw/day, there was no evidence of oncogenicity at any dose level. The lack of any evidence of oncogenicity supports the safety profile of the active ingredient in Seirogan, wood creosote.


2014 ◽  
Vol 13 (1) ◽  
pp. 66
Author(s):  
B. M. Jwad

Thirty Wistar albino rats of both sex, 1-1.25 months old (average body weight 250 – 300gm) were used. Animals were randomly divided into three groups. 1st group (acute group) n=10 given 0.5 ml. contain 500 mg/kg/body weight NaF, as single toxic dose via stomach tube. 2nd group (chronic group) n=10 given 0.5 ml. contain 150 mg/kg/body weight NaF via stomach tube daily for 60 days. 3rd group (control group) n=10 given 0.5 ml. physiological saline via a stomach tube. Clinical signs were reported during the course of the study, and then sacrificed after 3 and 7 days in 1st group, and 30 and 60 days in the 2nd group, then post-mortem examination was done, and any gross lesions were reported. Blood collected was done for biochemical examination (T3, T4, and TSH.) using special biochemical kits. Pieces of thyroid were taken, fixed in 10% formalin for 72 hours, and then all the specimens were processed and the histopathological changes were observed under light microscope. The pathological results showed hemorrhage appear in the capsular region of the thyroid gland with vacuolation in the cytoplasm of cell of a colloid with neutrophils infiltration in the lumen, as well as edema with fume cytoplasm and marked vacuolation of the cytoplasm of a colloid cell, also granulomatous lesion seated in gland parenchyma. That causes alteration of biochemical test T3, T4 and TSH in acute and chronic toxic doses.


2020 ◽  
Vol 13 (2) ◽  
Author(s):  
Sarah Hussain ◽  
Mariam Kadhem

The experiment was conducted to investigate the protective effect of Petroselinum crispum leave extracted against gentamicin-induced nephrotoxicity in male rabbits by studying the body weight, clinical signs, haematological and biochemical parameters, gross lesion and histopathological changes. Twenty four rabbits male were used and divided into 4 groups. Group 1: rabbits served as a negative control, received distilled water 1 ml(orally). Group 2: rabbits served as a positive control group, received gentamicin at a dose of 80 mg/kg/day intramuscular for 15 days. Group 3: rabbits received gentamicin at a dose of 80 mg/kg/day then after one hour treated with ethanolic extract of Petroselinum crispum at dose 125 mg/kg orally for 15 days. Group 4: rabbits received gentamicin at a dose of 80 mg/kg/day then after one hour treated with ethanolic extract of Petroselinum crispum at dose 250 mg/kg orally for 15 days.The results of the gentamicin treated group( positive control group) showed clinical signs such as loss of body weight, loss of appetite and rough hair with hematuria. The body weight a significantly declined (p≤ 0.05) compared other groups. There was a significant decrease (p≤ 0.05) in WBC count, lymphocyte, GSH, SOD, CAT, and GPX levels, while it recorded a significant increase (p≤0.05) in weights of the kidneys, neutrophils, creatinine, urea, and MDA. Histological studies showed several kidney pathological changes such as pale colour, enlargement in size and weight and easy from detaching as opposed to negative control group. On the other hand, the group treated with ethanolic extractof Petroselinum crispum at dose 125 mg/kg induced improved of parameters as recorded significant increased(P ≤ 0.05) in body weight, WBC count, lymphocyte, GSH, SOD, CAT, and GPX, while significant decreased (P ≤ 0.05) in weights of the kidneys, neutrophils, creatinine, urea, and MDA compared with the positive control group whereas rabbits treated with ethanolic extract of Petroselinum crispum at dose 250 mg/kg restored the parameters and histological changes of the kidney to near normal status compared with the negative control group. These results showed that the dose-detected Petroselinum crispum extract (250mg / kg) acts as potential curative effect against gentamicin-induced nephrotoxicity in male rabbits.


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