scholarly journals Toxicological evaluation of the ultrasonic extract from Dichroae radix in mice and wistar rats

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ling Wang ◽  
Zhiting Guo ◽  
Dongan Cui ◽  
Shahbaz Ul Haq ◽  
Wenzhu Guo ◽  
...  

Abstract This study was aimed at evaluating the acute and subchronic toxicity of ultrasonic extract of Dichroae radix (UEDR) in mice and rats. High performance liquid chromatography (HPLC) and thin layer chromatogrephy (TLC) were used to detect β-dichroine and α-dichroine in UEDR for quality control. The levels of β-dichroine and α-dichroine in UEDR were 1.46 and 1.53 mg/g, respectively. An oral LD50 of 2.43 g/kg BW was observed in acute toxicity test. After 28-day repeated oral administration, compared with the control group, treatment-related changes in body weight (BW) and body weight gain (BWG), lymphocyte counts and ratios, as well as in the relative organ weights (ROWs) of liver, kidney, lung, and heart, were detected in the middle- and high-dose groups (P < 0.05, P < 0.01), no differences were noted in the serum biochemical parameters and necropsy examinations in both sexes at all doses. Histopathological examinations exhibited UEDR-associated signs of toxicity or abnormalities. After 14 days withdrawal, no statistically significant or toxicologically relevant differences were observed in any of the UEDR-treated groups, and the hispathological lesions in the high-dose group were alleviated. Findings showed that long-course and high-dose of UEDR administration was toxic, and showed dose-dependence, the toxic damage was reversible.

2021 ◽  
Author(s):  
Priyanka Mathur ◽  
Shilpa Choudhary ◽  
Pradeep Bhatnagar

Abstract Pregnancy and feto-gestational toxicities on exposure to fluoride (F) and its possible amelioration on co-administration with Aloe-vera were studied in pregnant Swiss albino mice. Once the confirmed pregnancy was tested, animals were equally divided into four groups and were given following treatment. Group I was given no treatment and served as Control, Group II and III were administered sodium fluoride, 100 and 300 ppm respectively while group IV was co-administered with sodium fluoride, 300 ppm and Aloe-vera (300mg/kg) daily for 14 days prior to gestation and continued till the 18th day of gestation. Animals were sacrificed `on the 19th day of gestation for prenatal observations. Maternal body weight, the gravid uterine weight, number of corpora lutea in both the ovaries, number of implantations and resorptions, number of live (mature and immature ) male and female fetuses as well as number of dead fetuses were examined in each dam. The treatment continued in another set of animals till the completion of weaning period to observe postnatal changes due to test substances on the mother and pups. Sodium fluoride treated animals showed morphometric and skeletal changes which were more pronounced in the high dose group showing significantly decreased body weight gain in pregnant mothers; and dead/immature fetuses. Morphometric changes included open eyelids, limb defects, wrinkles on whole body, anophthalmias, pulmonary edema, enlarged esophagus and decreased body weight of fetuses and pups. Alizarin prepared skeletal structures of fetuses of such female mice showed delayed ossification or bending in number of bones of skull, thoracic and limb regions. However, concomitant exposure to Sodium Fluoride and Aloe-vera treated animals, there was a marked improvement in all the prenatal and postnatal variables. The study suggests that Sodium fluoride at the high concentrations may be teratogenic while co-administration of Aloe-vera during fluoride exposure might be beneficial in reducing these toxic effects. We thus recommend use of aloe vera as preventive agent or as a complimentary agent during fluoride treatment.


Author(s):  
M. K. Patel ◽  
D. J. Dave ◽  
R. C. Rathod ◽  
B. P. Joshi ◽  
D. J. Ghodasara

This work was conducted on six groups of day-old Cobb-400 broiler chicks to study the ameliorative effect of febuxostat on gout induced model. Clinical signs were noticed in birds of diclofenac control group II and low dose febuxostat treated group IV. During the study, 27.77% and 22.22% mortality were observed in diclofenac control group II and low dose febuxostat treated group IV, respectively. Febuxostat control group III and febuxostat (medium and high dose) treated groups V and VI had no mortality. Reduction in body weight gain and feed intake was observed in diclofenac control group II as compared to without treatment control group I at the end of every week during the experimental period of 21 days. Reduction in body weight gain and feed intake was observed in low dose febuxostat treated group IV as compared to control group at the end of 1st week. The average FCR was higher in diclofenac control group II (2.54) and low dose febuxostat treated group IV (2.14) as compared to control group (2.00). Kidney: body weight ratio was significantly high in diclofenac control group II as compared to control group at the end of experiment. Gross and microscopic lesions of visceral gout were mainly observed in chicks that died during the experiment from diclofenac control group II and low dose febuxostat treated group IV. The overall lesions showed that diclofenac was nephrotoxic and hepatotoxic in nature. Febuxostat at lower than the therapeutic dose did not prevent nephrotoxicity and hepatotoxicity caused by diclofenac leading to visceral gout. Febuxostat control III and febuxostat (medium and high dose) treated groups V and VI did not reveal any pathomorphological changes. Judicious use of febuxostat is safe in poultry birds between the limit of 4 mg/kg and 6 mg/kg


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jia-Ying Wu ◽  
Yuen-Cheung Chan ◽  
Hui Guo ◽  
Ying-Jie Chen ◽  
Yu-Xi Liu ◽  
...  

Abstract Background Herba Siegesbeckiae (HS), the dried aerial parts of Siegesbeckia orientalis L., S. pubescens Makino, or S. glabrescens Makino, is traditionally used for treating chronic diseases in China. However, there is no information about the chronic toxicity of HS. The objective of this study is to evaluate the 24-week oral dosing toxicities of HS aqueous extract (HSE) in rats. Methods S. orientalis-originated HS was reflux-extracted with distilled water. Sprague–Dawley rats were randomly divided into four groups, with 10 males and 10 females in each group. The rats were intragastrically administered with HSE at 5, 1.67 and 0.56 g/kg (experimental groups) or an equal volume of distilled water (control group), 6 days a week, for 24 weeks. The high dose of HSE (5 g/kg) was its maximum tolerated dose. Body weight was recorded every 2 days during the experimental period. Chemical, hematological and histopathological parameters, as well as organ weights, were measured at the end of the experiment. Results Decreased body weight gain; increased liver and lung relative weights; histopathological alterations in liver and lung tissues; elevated serum levels of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase were found after HSE treatments. In liver tissues, HSE treatment upregulated levels of three pro-inflammatory cytokines: IL-6, IL-1β and TNF-α. In lung tissues, HSE treatment caused oxidative stress and activated mitogen-activated protein kinases (MAPKs). Conclusion Long-term oral administration of HSE caused toxicities in rats evidenced by decreased body weight gain, as well as liver and lung damage. Treatment-induced oxidative stress, inflammation and MAPK activation are involved in HSE’s toxicities. Caution should be taken when using HS to treat chronic diseases.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ming-Nan Lai ◽  
Hui-Chen Hsu ◽  
Lean-Teik Ng

Abstract Background Xylaria nigripes (Koltz.) Cooke, also known as Wuling Shen, is a high-value medicinal mushroom. It is a herbal medicine traditionally used for treating insomnia, trauma and depression. However, its toxicity has never been systematically evaluated. This study aimed to evaluate the safety of a standardized aqueous extract (XNE), an ingredient of commercial products, prepared from solid-state cultured X. nigripes in rats. Methods A 90-day subchronic toxicity study was conducted by oral administration of XNE at daily doses of 20, 1000 and 2000 mg/kg body weight to Sprague-Dawley rats of both sexes, and the control group was given distilled water (vehicle). All animals were checked daily for general behavior, body weight changes and signs of toxicity. At the end of the treatment period, hematological analysis, biochemical analysis and histopathological examination of organs were conducted. Results At tested concentrations, oral XNE administration caused no treatment-induced adverse effects on general health, body weight gain, relative organ weights, and hematological and biochemical parameters. Histopathological results also showed no significant structural changes in organs even in high-dose XNE-treated animals. Conclusion This study suggests that treatment with XNE for 90 days does not produce significant toxicity, even up to 100 fold (2000 mg/kg body weight/day) of the recommended daily intakes. Therefore, the use of XNE as herbal medicines is considered to be relatively safe.


2014 ◽  
Vol 84 (1-2) ◽  
pp. 5-11 ◽  
Author(s):  
Eun Y. Jung ◽  
Sung C. Jun ◽  
Un J. Chang ◽  
Hyung J. Suh

Previously, we have found that the addition of L-ascorbic acid to chitosan enhanced the reduction in body weight gain in guinea pigs fed a high-fat diet. We hypothesized that the addition of L-ascorbic acid to chitosan would accelerate the reduction of body weight in humans, similar to the animal model. Overweight subjects administered chitosan with or without L-ascorbic acid for 8 weeks, were assigned to three groups: Control group (N = 26, placebo, vehicle only), Chito group (N = 27, 3 g/day chitosan), and Chito-vita group (N = 27, 3 g/day chitosan plus 2 g/day L-ascorbic acid). The body weights and body mass index (BMI) of the Chito and Chito-vita groups decreased significantly (p < 0.05) compared to the Control group. The BMI of the Chito-vita group decreased significantly compared to the Chito group (Chito: -1.0 kg/m2 vs. Chito-vita: -1.6 kg/m2, p < 0.05). The results showed that the chitosan enhanced reduction of body weight and BMI was accentuated by the addition of L-ascorbic acid. The fat mass, percentage body fat, body circumference, and skinfold thickness in the Chito and Chito-vita groups decreased more than the Control group; however, these parameters were not significantly different between the three groups. Chitosan combined with L-ascorbic acid may be useful for controlling body weight.


2021 ◽  
Vol 82 (1) ◽  
Author(s):  
Kavita Shirsath ◽  
Apeksha Joshi ◽  
Aliasgar Vohra ◽  
Ranjitsinh Devkar

Abstract Background Circadian disruption is often associated with aggravation of atherosclerosis; however, the pathophysiological mechanisms underlying atherogenic initiation in normolipidemic diet remains unclear. Most of the studies done for understanding circadian disruption induced atherosclerosis have been carried out in murine model of hyperlipidemia induced atherosclerosis. The present study investigates pro-atherogenic events in response to chronic photoperiodic manipulation induced chronodisruption (PMCD) in C57BL/6J mice fed with laboratory chow diet. Results The results were compared with atherogenic initiation induced by high fat high fructose (HFHF) diet. The combined effects of HFHF and PMCD on atherogenic initiation were also investigated for possible synergy of both variants. The HFHF and HFHF+PMCD groups recorded increments in body weight gains and serum lipid parameters (TC, TG, LDL-cholesterol, VLDL) and a decrement in HDL-cholesterol as compared to the control group. However, PMCD group recorded body weight gain similar to that of the control group, but the serum lipid parameters (TG and VLDL) were significantly elevated and the HDL levels were lowered. However, prominent hypertrophic remodeling, higher collagen deposition, and elastin derangement, along with endothelial dysfunction, its activation, and macrophage infiltration, were observed in thoracic aorta of all the three experimental groups. But the mRNA and immunoblots of heat shock protein 60 (HSP60) in thoracic aorta was found to be maximum in PMCD followed by HFHF and HFHF+PMCD groups. Conclusion Laboratory chow feeding coupled with photoperiodic manipulation mediated chronodisruption overexpress HSP60 that in turn plays a central role in PMCD mediated pro-atherogenic remodeling in thoracic aorta of C57BL/6J mice.


1996 ◽  
Vol 271 (1) ◽  
pp. R48-R54 ◽  
Author(s):  
K. Ackroff ◽  
A. Sclafani

Orlistat (Ols), a potent inhibitor of pancreatic lipase, was added to the fat source (1 or 4 mg Ols/g fat) of a macronutrient self-selection diet fed to adult female rats. The rats responded to the drug-induced reduction in fat absorption by decreasing their dietary fat intake and increasing their protein and carbohydrate intake in a dose-related manner. Total caloric intake also increased, but body weight gain was inhibited compared with the nondrug control group. When Ols was removed from the diet, nutrient selection, caloric intake, and body weight returned to control levels. In additional short-term experiments (30 min/day), rats developed a preference for a plain fat diet over an Ols-fat diet (4 mg/g fat) and also for a cue flavor paired with plain fat over a flavor paired with Ols-fat. Yet, when not given the choice, the rats consumed nearly as much Ols-fat as plain fat diet. These results indicate that, by reducing fat absorption, Ols reduced the attractiveness of dietary fat, although it did not make the fat diet aversive. In clinical use, lipase inhibitors may be effective in reducing dietary fat intake by reducing both the consumption and absorption of fat.


2013 ◽  
Vol 49 (1) ◽  
pp. 135-148 ◽  
Author(s):  
Fernando Márlisson de Queiroz ◽  
Kayo Wanderson de Oliveira Matias ◽  
Mylena Mylana Freire da Cunha ◽  
Aline Schwarz

Phyllanthus niruri L. (Euphorbiaceae), known as "quebra-pedra" (Portuguese for "stonebreaker"), is an herb used for kidney disorders. In light of its frequent use by the population, the present study aimed to investigate the genotoxic, antigenotoxic and cytotoxic activities of a standardized P. niruri extract in bone marrow rats. Three groups of 12 animals were treated daily by gavage over a period of 30 days, with 50, 150 or 250 mg/kg of P. niruri extract aqueous solution. The control group (n = 12) received tap water. At the end of treatment (day 31), groups were divided into two minor subgroups (n=6/group) and received cyclophosphamide (50 mg/kg, i.p.) or saline 0.9% (i.p.). After 24 hours, we evaluated the frequency of micronucleated polychromatic erythrocytes for each animal (MNPCE) at 1000 PCE. Cytotoxicity was evaluated with the PCE/NCE ratio (NEC = normochromatic erythrocytes). General toxicity was assessed during treatment using the parameters of body weight gain, ration and water consumption. The dry extract did not provoke changes in body weight, weight gain, ration and water intake or changes in the frequency of MNPCE or cytotoxicity in bone marrow. We propose that the P. niruri extract used here showed no genotoxic, antigenotoxic and cytotoxic activities under the experimental conditions.


2014 ◽  
Vol 59 (1) ◽  
pp. 475-481 ◽  
Author(s):  
Michael J. Schlosser ◽  
Hiromi Hosako ◽  
Ann Radovsky ◽  
Mark T. Butt ◽  
Dragomir Draganov ◽  
...  

ABSTRACTTedizolid, a novel oxazolidinone antibacterial, was administered to Long Evans rats by oral gavage once daily for up to 9 months at doses near the maximum tolerated dose (MTD) to evaluate for potential neurotoxicity. Mean plasma exposures of tedizolid at the low-, medium-, and high-dose levels (7.5, 15, and 30 mg/kg of body weight/day for males; 2.5, 5, and 10 mg/kg/day for females) were similar between males and females and were 1.8-, 3.9-, and 8.0-fold greater than exposures in patients at the therapeutic dose (200 mg once daily). Evaluated endpoints included survival, clinical observations, body weight, and food consumption. At 1, 3, 6, and 9 months, ophthalmic examinations, functional observational batteries, and locomotor activity measures were conducted, brain weights/sizes were recorded, and perfusion-fixed tissues were collected from 12 rats/sex/group/time point. A detailed morphological assessment was conducted on brain, eyes, optic nerve/tract, spinal cord, peripheral nerves (includes sciatic, sural, tibial, peroneal, trigeminal), and skeletal muscle. At the end of 9 months, less body weight gain was seen in high-dose males (−6.7%) and females (−5.8%) compared with that seen in controls. There were no tedizolid-related adverse neurobehavioral effects or tedizolid-related histopathologic changes in the central/peripheral nervous systems, including the optic nerve. Results of this study indicate that tedizolid was not neurotoxic when administered long term to pigmented rats at doses near the MTD, which were up to 8-fold higher than the human therapeutic exposure.


2012 ◽  
Vol 27 (8) ◽  
pp. 537-543 ◽  
Author(s):  
Lívia Hipólito Cardozo Brant ◽  
Ludmila Ferreira Medeiros de França Cardozo ◽  
Luís Guillermo Coca Velarde ◽  
Gilson Teles Boaventura

PURPOSE: To evaluate whether the prolonged consumption of flaxseed minimize the factors that trigger MS in healthy rats. METHODS: Pregnant rats were divided immediately after delivery into two groups during the lactation period, a control group (CG) receiving casein-based diet with 17% of protein, and a Flaxseed group (FG) with casein-based diet plus 25% of flaxseed. At weaning, 12 offspring of each group continued to receive the same feed but with 10% of protein up to 200 days old. RESULTS: FG showed a significant reduction in body weight (p=0.001), total cholesterol levels (p<0.0001), triglycerides (p=0.0001), and glucose (p=0.001). CONCLUSION: The flaxseed alters the indicators related to development of metabolic syndrome, because it has beneficial effects on lipids and glucose profiles and prevents the excess of body weight gain.


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