scholarly journals Dimethylarsenic acid (DMA) accumulation positively correlates with realgar-induced subchronic toxicity in rats

2018 ◽  
Author(s):  
Yan Yi ◽  
Shuangrong Gao ◽  
Jing Xia ◽  
Yong Zhao ◽  
Chunying Li ◽  
...  
Keyword(s):  
Kidney Tissue ◽  
Arsenic Species ◽  
The Body ◽  
Control Group ◽  
Clinical Dose ◽  
Clinical Observations ◽  
Target Organs ◽  
Adverse Effect Level ◽  
Liver And Kidney ◽  
Effect Level

AbstractThe toxicity of realgar depends largely on different arsenic species accumulation and distribution in the body. Here, after continuous oral administration of different doses of realgar for 90 days and subsequent 60-day withdrawal period, clinical observations, food consumption, body weights, blood biochemistry, hematology, and histomorphological examination of rats were performed. Realgar 40mg·kg−1·d−1 and 170 mg·kg−1·d−1 of realgar (which is equivalent to 40-fold and 100-fold the maximum clinical dose, respectively) can cause toxicity in rats, including degreased body weight, peripheral blood neutrality abnormal ratio of granulocytes and lymphocytes, hypercoagulability of the blood, liver and kidney tissue damage, liver and kidney may be the main toxic target organs of realgar. The no observed adverse effect level (NOAEL) dose is 10 mg·kg−1. At the same time, the content and distribution of arsenic species in tissues were determined. The content of total arsenic (tAs) and Dimethylarsenic acid (DMA) in the tissues of the realgar group was significantly higher than those of the control group. After 60 days of discontinuation, the DMA content in the realgar group decreased, but it was still higher than that in the control group, and liver and kidney damage occurred during the administration period basically returned to normal. Therefore, the authors speculated that when the DMA content in the tissue exceeds a certain range, liver and kidney toxicity will be induced. However, when the DMA content is lower than the above threshold after drug withdrawal, the liver and kidney lesions can return to normal.

scholarly journals Single-dose and 4-week repeated dose Toxicity of Aconitum Sinomontanum Nakai Pharmacopuncture: An Experimental Study

2021 ◽  
Vol 38 (1) ◽  
pp. 47-59
Author(s):  
Sang Ha Woo ◽  
Jung Hee Lee ◽  
Cho-in Lee ◽  
Yun Kyu Lee ◽  
Hyun-Jong Lee ◽  
...  
Keyword(s):  
Single Dose ◽  
Normal Saline ◽  
Repeated Dose ◽  
Control Group ◽  
Weight Changes ◽  
Significant Toxicity ◽  
Repeated Dose Toxicity ◽  
Adverse Effect Level ◽  
Liver And Kidney ◽  
Effect Level

Background: This study aimed to assess the toxicity of Aconitum sinomontanum Nakai (ASN) pharmacopuncture.Methods: To investigate the toxicity of ASN pharmacopuncture, single and 4-week repeated dose toxicity experiments were conducted on BALB/c mice. In the single-dose toxicity experiment, mice were assigned 1 of 4 groups (5 males, 5 females per group). Then, 31.25, 62.5, and 125 mg/kg of ASN pharmacopuncture were administered to the mice in the experimental groups at acupoint ST36, while 0.2 mL of normal saline was administered to the control group at ST36. After a 4-week repeated dose regimen, the mice were assigned into 4 groups (5 males, 5 females per group). Then, 15.625, 31.25, and 62.5 mg/kg of ASN pharmacopuncture at ST36 were administered to the mice in the experimental groups, while 0.2 mL of normal saline was administered to the control group at ST36. Mortality, morbidity, general body and organ weight changes (after 4 weeks repeated dose), serum hematological and biochemical values, and histopathological changes in the liver and kidney were observed.Results: In both single and 4-week repeated dose toxicity experiments, no deaths or symptoms occurred in any of the groups. There were no significant differences between groups in terms of body and organ weights, serum hematological and biochemical values, and specific organ histopathological changes.Conclusion: ASN pharmacopuncture injection did not demonstrate significant toxicity in BALB/c mice compared with the control group, with a no-observed-adverse-effect level for a single dose of >125 mg/kg, and for 4 weeks repeated dose it was more than 62.5 mg/kg/day

Effect of inorganic and organic manganese supplementation on the performance and tissue manganese content of broiler chicks

2004 ◽  
Vol 52 (2) ◽  
pp. 199-209 ◽  
Author(s):  
Erzsébet Berta ◽  
Emese Andrásofszky ◽  
A. Bersényi ◽  
R. Glávits ◽  
A. Gáspárdy ◽  
...  
Keyword(s):  
Manganese Content ◽  
Kidney Tissue ◽  
The Body ◽  
Control Group ◽  
Broiler Chicks ◽  
Tissue Analysis ◽  
Liver And Kidney ◽  
G Ratio ◽  
Soybean Diet ◽  
Mn Concentrations

The effects of dietary levels of manganese (Mn) in inorganic (MnO) and organic (Mn fumarate) forms were evaluated on cockerel chicks. A basal corn-soybean diet with 23 mg/kg Mn was supplemented with levels of 0, 30, 60 and 240 ppm Mn from both Mn sources. Each treatment was replicated in five pens of 10 chicks. The chicks were fed diets ad libitum from 14 to 49 days of age, after which five birds per treatment were sacrificed for pathomorphological examinations and analysis. The treatments did not exert significant effects on the body weight (BW), the feed/gain (F/G) ratio or the mortality rate. According to the necropsy findings, no growth retardation or emaciation occurred in either of the groups and the differences in the average absolute and relative organ weights were not significant (P ? 0.05). Tissue analysis indicated that the tibia showed the greatest response to Mn, followed by the liver and kidney. Accumulation in the tibia was higher (P < 0.05) with supplements of 30, 60 and 240 mg/kg from both Mn sources (3.71, 3.78, 4.44, and 3.68, 4.00, 4.36 mg/kg DM, MnO and Mn fumarate, respectively) compared to the control group (3.21 mg/kg). Accumulation in the liver increased significantly (P < 0.05) only with supplements of 60 and 240 ppm independently of the Mn source (12.7, 14.2, and 14.0, 14.9 mg/kg, respectively) compared to the control (9.8 mg/kg). Similarly, kidney tissue Mn was higher (P < 0.05) only with supplements of 60 and 240 ppm (12.8, 12.8, and 13.1, 12.5 mg/kg, respectively) compared to the control (10.2 mg/kg). At the same level of supplementation of the two Mn sources there were no significant differences (P ? 0.05) between the Mn concentrations of organs and tissues. Droppings sensitively reflected the intake, whereas blood plasma and feathers showed only the extreme Mn loading.

scholarly journals Efficacy of Caffeic Acid on Diabetes and Its Complications in the Mouse

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3262
Author(s):  
Nada Oršolić ◽  
Damir Sirovina ◽  
Dyana Odeh ◽  
Goran Gajski ◽  
Vedran Balta ◽  
...  
Keyword(s):  
Lipid Profile ◽  
Caffeic Acid ◽  
Fasting Blood Glucose ◽  
Kidney Tissue ◽  
Serum Glucose ◽  
The Body ◽  
Diabetic Mice ◽  
Atherogenic Indices ◽  
Liver And Kidney ◽  
Hematological And Biochemical Parameters

Diabetic dyslipidemia and hyperglycemia contribute to excessive reactive oxygen species (ROS) production, leading to deleterious complications, such as nephropathy, atherosclerosis and cardiac dysfunction, and target major organs in the body. The aim of this study was to investigate the effect of caffeic acid (CA) on mouse weight and survival, serum level of fasting blood glucose (FBG), serum lipid parameters and atherogenic indices, oxidative damage in blood, liver and kidney tissue, pathophysiological changes and their function markers in healthy and alloxan-induced type 1 diabetic mice. Diabetes was induced in mice with a single intravenous injection of alloxan (75 mg kg−1). Two days later, CA (50 mg kg−1) was given intraperitoneally for seven days in diabetic mice. Diabetes affected glucose level, lipid profile, hematological and biochemical parameters, induced DNA damage and apoptotic/necrotic death in whole blood cells, liver and kidney, leading to weight loss and a decreased lifespan. CA treatment of diabetic mice revealed a protective effect on the liver and kidney, hypoglycemic and hypolipidemic properties and high protection against atherogenic outcomes. The obtained results suggest that CA is a safe and potent agent against diabetes that acts as an effective antioxidant in reducing serum glucose, lipid profile and atherogenic indices, leading to increased lifespan in mice.

Safety of a novel galacto-oligosaccharide: Genotoxicity and repeated oral dose studies

2009 ◽  
Vol 28 (10) ◽  
pp. 619-630 ◽  
Author(s):  
T. Kobayashi ◽  
N. Yasutake ◽  
K. Uchida ◽  
W. Ohyama ◽  
K. Kaneko ◽  
...  
Keyword(s):  
Oral Dose ◽  
Kluyveromyces Lactis ◽  
Clinical Signs ◽  
Chinese Hamster ◽  
Metabolic Activation ◽  
Blood Chemistry ◽  
Control Group ◽  
Sprague Dawley ◽  
Adverse Effect Level ◽  
Effect Level

A series of safety tests were undertaken on a novel galacto-oligosaccharide (GOS) produced from lactose by a two-step enzymatic process involving Sporobolomyces singularis and Kluyveromyces lactis. Bacterial reverse mutation and chromosomal aberration tests, with or without metabolic activation, were performed. These tests showed no mutagenesis in the Ames assay or in Escherichia coli WP2uvrA, and no chromosomal aberrations in cultured fibroblast cells from Chinese hamster lungs (CHL/IU). Micronuclei were not induced in the reticulocytes of mouse peripheral blood following oral administration of GOS. In a 90-day repeated oral dose toxicity study in rats, GOS was administered at 0, 500, 1000 and 2000 mg/kg to male and female Sprague-Dawley rats. There were no GOS-related changes in clinical signs, body weight, water intake, feed intake, urinalysis, ophthalmology, haematology, blood chemistry, organ weights, gross pathology or histopathology in any of the treatment groups compared to the control group. The no observed adverse effect level (NOAEL) of GOS was at least 2000 mg/kg/day in both males and females.

scholarly journals Beagle dog 90-day oral toxicity study of a novel coccidiostat – ethanamizuril

2020 ◽  
Author(s):  
Keyu Zhang ◽  
Xiaoyang Wang ◽  
Shuya Wei ◽  
Chunmei Wang ◽  
Mi Wang ◽  
...  
Keyword(s):  
Clinical Pathology ◽  
Dosage Level ◽  
Oral Toxicity ◽  
Safety Database ◽  
Clinical Observations ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Anticoccidial Activity ◽  
Anticoccidial Agent ◽  
Histologic Changes

Abstract Background: Triazine coccidiostats are widely used in chickens and turkeys for coccidiosis control. Ethanamizuril is a novel triazine compound that exhibits anticoccidial activity in poultry. To support the safety assessment of the new potent anticoccidial agent, the subchronic toxicity of ethanamizuril was studied in beagle dogs administered ethanamizuril by diet at doses of 12, 60 or 300 mg/kg/day for 90 days.Results: Ethanamizuril was well tolerated at low and middle dosages and there were no ethanamizuril related effects on survival, clinical observations, clinical pathology parameters, organs weight, macroscopic or microscopic evaluations. The ethanamizuril related changes were limited to effects on food consumption and histologic changes of kidneys in the 300 mg/kg/day group in both sexes. However, the characteristic toxicities of ethanamizuril in kidneys are recoverable in convalescence dogs of 300 mg/kg/day group. Conclusions: Therefore, the no-observed-adverse-effect level (NOAEL) was considered to be 60 mg/kg/day, the middle dosage level tested. These results add to the safety database for ethanamizuril with potential for use as a novel coccidiostat.

scholarly journals Prophylactic effect of vitamin E against hepatotoxicity, nephrotoxicity, haematological indices and histopathology induced by diazinon insecticide in mice

2009 ◽  
Vol 55 (3) ◽  
pp. 219-226 ◽  
Author(s):  
Nahla S. El-Shenawy ◽  
Rasha A. Al-Eisa ◽  
Fawzia El-Salmy ◽  
Omema Salah
Keyword(s):  
Body Weight ◽  
Vitamin E ◽  
Kidney Function ◽  
Kidney Tissue ◽  
The Body ◽  
High Dose ◽  
Protective Effects ◽  
Histopathological Changes ◽  
Liver And Kidney ◽  
Haematological Indices

Abstract Considering that the involvement of reactive oxygen species (ROS) has been implicated in the toxicity of various pesticides, this study was designed to study the ameliorative effect of Vitamin E (100 mg/kg body weight) on mice (25 - 30 mg) treated with diazinon (32.5 or 16.25 mg/kg body weight) organophosphate insecticide for 14 days. Subchronic DZN exposure and the protective effects of vitamins E (vitE) were evaluated for their effects on haematological indices, the enzymes concerning liver damage [plasma alanine aminotransferase (ALT), aspartate aminotaransferase (AST), alkaline phosphatise (AIP), and some parameters of kidney function (urea and creatinine) in mice. Additionally, the histopathological changes in liver and kidney tissue were examined. The high dose of diazinon (DZNH) decreased the body weight significantly at the end of experiment. Additionally, the liver and kidney were examines for histopathological changes. The high dose of diazinon decreased body weight significantly. Moreover, there was a statistically significant decrease in haemoglobin (Hb), red blood cell (RBC) and hematocrit (Hct) in diazinon-treated mice compared to controls. This decrease was partially remedied in the diazinon-treated group that also received vitE. Damage in the liver and kidney tissues was also evident as elevated plasma ALT, AST, ALP, urea and creatinine. VitE partially counteracts the toxic effect of DZN and repairs tissue damage in the liver and kidney, especially when supplemented to 1/4 LD50 intoxicated animals. Histopathological changes in liver and kidney were observed only in 32.5 mg/kg DZN given group. These results suggest that the effects of DZN are dose dependent. No pathological findings were observed in vitE + DZN treated groups. According to the present study, we conclude that vitE can reduce the detrimental impacts of diazinon on haematological indicies, as well as liver and kidney function.

scholarly journals Imbalance in the Blood Concentrations of Selected Steroids in Pre-pubertal Gilts Depending on the Time of Exposure to Low Doses of Zearalenone

Toxins ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 561 ◽  
Author(s):  
Anna Rykaczewska ◽  
Magdalena Gajęcka ◽  
Ewa Onyszek ◽  
Katarzyna Cieplińska ◽  
Michał Dąbrowski ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Biological Effect ◽  
Control Group ◽  
Low Doses ◽  
Blood Concentrations ◽  
Qualitative And Quantitative ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Quantitative Changes ◽  
Control Group Group

Zearalenone (ZEN) is a mycotoxin that not only binds to estrogen receptors, but also interacts with steroidogenic enzymes and acts as an endocrine disruptor. The aim of this study was to verify the hypothesis that low doses, minimal anticipated biological effect level (MABEL), no-observed-adverse-effect level (NOAEL) and lowest-adverse-effect level (LOAEL), of ZEN administered orally for 42 days can induce changes in the peripheral blood concentrations of selected steroid hormones (estradiol, progesterone and testosterone) in pre-pubertal gilts. The experiment was performed on 60 clinically healthy gilts with average BW of 14.5 ± 2 kg, divided into three experimental groups and a control group. Group ZEN5 animals were orally administered ZEN at 5 μg ZEN/kg BW, group ZEN10 — at 10 μg ZEN/kg BW, group ZEN15 — at 15 μg ZEN/kg BW, whereas group C received a placebo. Five gilts from every group were euthanized on analytical dates 1, 2 and 3 (days 7, 14 and 42 of the experiment). Qualitative and quantitative changes in the biotransformation of low ZEN doses were observed. These processes were least pronounced in group ZEN5 (MABEL dose) where ZEN metabolites were not detected on the first analytical date, and where β-ZEL was the predominant metabolite on successive dates. The above was accompanied by an increase in the concentration of estradiol (E2) which, together with “free ZEN”, probably suppressed progesterone (P4) and testosterone (T) levels.

Lack of Trigeminal Nerve Toxicity in Rats Exposed to Trichloroethylene Vapor for 13 Weeks

2006 ◽  
Vol 25 (6) ◽  
pp. 531-540 ◽  
Author(s):  
Ralph R. Albee ◽  
Pamela J. Spencer ◽  
Keith A. Johnson ◽  
Greg J. Bradley ◽  
Brian R. Marable ◽  
...  
Keyword(s):  
Trigeminal Nerve ◽  
Auditory Brainstem ◽  
Female Rats ◽  
Male Rats ◽  
Fischer 344 ◽  
Clinical Observations ◽  
Body Weights ◽  
Adverse Effect Level ◽  
Brainstem Response ◽  
Effect Level

Male and female Fischer-344 rats were exposed to 1,1,2-trichloroethylene (TCE) at 250, 800, or 2500 ppm for 6 h/day, 5 days/week, for 13 weeks. Weekly body weights and daily clinical observations were recorded and a functional observational battery (FOB) was performed monthly. Postexposure neurotoxicological evaluations included an electrodiagnostic evaluation of auditory function, the trigeminal nerve, and a comprehensive neuropathological examination. After 8 weeks of exposure, female, but not male, rats exposed to 2500 ppm were slightly more reactive to handling than the controls but not after 13 weeks of exposure. After 13 weeks, female rats exposed to 2500 ppm TCE were slightly more active during the 1-min observation period than the controls. There were no treatment-related differences in grip performance, landing foot splay, or on the trigeminal nerve–evoked potential at any dose. At 2500 ppm TCE, mild frequency-specific hearing deficits were observed, including elevated tone-pip auditory brainstem response thresholds. Focal loss of hair cells in the upper basal turn of the cochlea was observed in 2500 ppm–exposed rats. Except for the cochleas of 2500 ppm–exposed rats, no treatment-related lesions were noted during the neuro-histopathologic examination. The no-observable-adverse-effect level for this study was 800 ppm based on ototoxicity at 2500 ppm.

scholarly journals Does Oral Ingestion ofPiper sarmentosumCause Toxicity in Experimental Animals?

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Maizura Mohd Zainudin ◽  
Zaiton Zakaria ◽  
Nor Anita Megat Mohd Nordin ◽  
Faizah Othman
Keyword(s):  
Safety Information ◽  
The Body ◽  
Control Group ◽  
Sprague Dawley ◽  
Internal Organs ◽  
Haematological Profile ◽  
Daily Dose ◽  
Liver And Kidney ◽  
Prevalence Of Diabetes Mellitus ◽  
Herbal Plant

The prevalence of diabetes mellitus has reached epidemic proportion in Malaysia and worldwide. Scientific studies have shown that herbal plantPiper sarmentosumexhibits an antidiabetic property. Despite the extensive usage and studies of this herb as alternative medicine, there is paucity of the literature on the safety information of this plant. Thus, the present study aimed to observe the subacute toxic effects ofPiper sarmentosumaqueous extract (PSAE) on the haematological profile, liver, and kidney in rats. The extract was administered by oral gavage to 6 male and femaleSprague Dawleyrats in daily dose of 50 mg/kg, 300 mg/kg, and 2000 mg/kg for 28 consecutive days. The control group received normal saline. General behavior of the rats, adverse effects, and mortality were observed for 28 days. The haematological and biochemical parameters were determined at baseline and after the treatment. PSAE did not show abnormality on the body weight and gross observation of internal organs. The haematological, biochemical and histopathological profiles showed minimal changes and variation within normal clinical range except for significant increase in serum potassium level that suggests the need of regular monitoring. Nevertheless, these findings suggested that PSAE up to 2000 mg/kg/day did not show subacute toxicity inSprague Dawleyrats.

Accumulation of cadmium with time in Romney sheep grazing ryegrass-white clover pasture: effect of cadmium from pasture and soil intake

1996 ◽  
Vol 47 (6) ◽  
pp. 877 ◽  
Author(s):  
J Lee ◽  
JR Rounce ◽  
AD Mackay ◽  
ND Grace
Keyword(s):  
Management Strategies ◽  
Kidney Tissue ◽  
Total Content ◽  
Control Group ◽  
Fresh Tissue ◽  
Cd Accumulation ◽  
Adaptive Effect ◽  
Liver And Kidney ◽  
Free Body ◽  
Kidney Liver

Cadmium (Cd) concentrations in various tissues of Romney sheep and rates of accumulation, as affected by Cd concentrations in pasture and soil, DM intake, and animal age, were determined in a 25-month study. After weaning, 6 groups of 10 wether lambs were grazed on a low Cd (0.l8 � 0.08 8g Cd/g DM) or high Cd (0.52 � 0.17 8g Cd/g DM) pasture in 3 replicates. The rate of accumulation of Cd (8g /day) into the liver and kidney was greatest in sheep aged about 6 months (for the low and high Cd pastures: kidney 0.27 and 0.56; liver 0.35 and 1 I), after which it declined with age (kidney 0.02 and 0.03: liver <0901 and 0.05; at 28 months of age). Total content of Cd in the organs continued to increase. In 6-month-old animals, 0.25% of total Cd ingested was retained by the kidney and liver, but this proportion decreased to about 0.05% of Cd intake with 28-month-old animals. Net retention of Cd in the fleece-free body as a percentage of daily Cd intake for both the control and treatment animals was estimated between 0- 35 and 0 5%. Except for muscle tissue from sheep in the treatment group, for which the mean Cd concentration was lower than that of the control group (2.0 � 0.24 and 3 9 � 0.63 r)g Cd/g fresh tissue, respectively), Cd concentrations in kidney, liver, thymus, muscle, and lung tissue increased over the first 3 months for both groups of animals. After 2 years, animals on the treatment pastures had approximately 3-fold greater Cd concentrations in liver, kidney, and duodenal tissue tissue than those grazing the control pastures (liver, 361 � 58 v. 97 � 11; kidney, l485 � 200 v. 352f48; duodenal tissue, 32f 4 v. 18f 2.5 t)g Cd/g FW, respectively). At higher Cd intakes, the adaptive effect of increased metallothionein synthesis enabled the animal to be more efficient in binding Cd, which restricted accumulation of Cd in muscle. The regression ([Cd] kidney = -205 + 0. 981Cdintake + 0 - 726Time; r = 0.82, P < 0.001) gave the best fit for the observed Cd concentration in the kidney tissue. Daily Cd intake was also a better predictor of the Cd concentration in liver tissue than the concentration of Cd in pasture by itself ([Cd]liver, = 24.7 + 0.353Cdintake; r = 0.81, P < 0.001). Accurate predictions of the potential for Cd accumulation in young grazing animals will enable more effective management strategies to be implemented to reduce Cd accumulation and therefore minimise the potential impact relating to both environment and market.

Sign in / Sign up

Export Citation Format

Share Document