Combined repeated-dose and reproductive/developmental toxicity screening test of 1-tert-butoxy-4-chlorobenzene in rats

We have carried out animal toxicity tests of chemicals for a chemical safety program implemented by the Ministry of Economy, Trade, and Industry of Japan. Here, we tested 1-tert-butoxy-4-chlorobenzene in a combined repeat-dose and developmental and reproductive toxicity test. The test chemical was administered daily by gavage to 9-week-old Crl:CD (SD) rats at doses of 0, 20, 100, and 500 mg/kg/d. Males were treated for 42 d beginning 14 d before mating. Females were treated from 14 d before mating to day 4 of lactation. Decreased spontaneous locomotion, decreased respiratory rate, and incomplete eyelid opening were observed at 500?mg/kg/d (both sexes), but resolved within 30?min of administration, suggesting central nervous system depression. No notable changes were observed in body weight, food consumption, functional battery tests, or blood test. Increased liver weight with centrilobular or diffuse hepatocyte hypertrophy was observed at 100 and 500?mg/kg/d (both sexes). There were no biochemical or histopathological changes related to hepatotoxicity. Increased kidney weight with basophilic tubules, tubule dilatation, and increased hyaline droplets were observed in males dosed at 100 and 500?mg/kg/d. Immunohistochemical staining indicated α_2u-globulin nephropathy, a male rat-specific toxicity. Although kidney weight was also increased in females dosed at 500?mg/kg/d, it was not considered to be an adverse effect because there were no histopathological changes. Pup weights on postnatal day 0 were decreased at 500?mg/kg/d and still decreased on postnatal day 4. Our data indicated the no-observed-adverse-effect-level for repeated-dose and reproductive/developmental toxicity for 1-tert-butoxy-4-chlorobenzene was 100?mg/kg/d.     

Acute and subchronic dermal toxicity of Vitex negundo essential oil

Vitex negundo is a common herb in different herbal formulation. The potential acute and sub-chronic dermal toxicities were evaluated as per OECD (Organization for Economic Cooperation and Development) guidelines 402 and 411, respectively. Both sexes of Wistar rats were exposed to Vitex negundo oil of 2000?mg/kg body weight for acute dermal toxicity, whereas in the dermal sub-chronic toxicity study, rats were exposed to Vitex negundo oil 250, 500 and 1000?mg/kg body weight, respectively, for five times a week for 90?d. In acute and sub-chronic toxicity studies, all animals were normal without any behavioral, serum biochemistry, hematology, necroscopical and histopathological changes. The no observed effect level (NOEL) and no observed adverse effect level (NOAEL) of Vitex negundo oil were 250 and 1000?mg/kg/day, respectively. Vitex negundo oil is under the category 5 (Unclassified) according to the Globally Harmonized System, with an LD₅₀ value of over 2000?mg/kg.     

Mutagenicity and preclinical safety assessment of the aqueous extract of Clinacanthus nutans leaves

Context: Clinacanthus nutans (CN) is used traditionally for treating various illnesses. Robust safety data to support its use is lacking. Objective: To evaluate the adverse effects of aqueous extract of CN leaves (AECNL). Materials and methods: The oral toxicity of the AECNL was tested following Organisation for Economic Co-operation and Development (OECD) guidelines. Mutagenicity (Ames test) of AECNL was evaluated using TA98 and TA100 Salmonella typhimurium strains. Results: No mortality or morbidity was found in the animals upon single and repeated dose administration. However, significant body weight loss was observed at 2000?mg/kg during sub-chronic (90 d) exposure. In addition, increased eosinophil at 500?mg/kg and decreased serum alkaline phosphatase levels at 2000?mg/kg were observed in male rats. Variations in glucose and lipid profiles in treated groups were also observed compared to control. Ames test revealed no evidence of mutagenic or carcinogenic effects at 500?μg/well of AECNL. Conclusion: The median lethal dose (LD₅₀) of the AECNL is >5000?mg/kg and the no-observed-adverse-effect level is identified to be greater than 2000?mg/kg/day in 90-d study.     

Prenatal developmental toxicity evaluation of Withania somnifera root extract in Wistar rats

Context: Withania somnifera (L) Dunal (Solanaceae) is an important traditional herbal medicine used for thousands of years and is considered as the Indian ginseng. Reports on the effect of Withania somnifera root (WSR) extract on the developing foetus of pregnant rats including mortality, structural abnormalities, changes in growth and effects on dams are not available. Objective: The present study was performed to evaluate the prenatal developmental toxicity potential of WSR extract in rats. Materials and methods: WSR extract was given orally to pregnant rats during the period of major organogenesis and histogenesis (days 5 to 19 of gestation) at the dose levels of 500, 1000 and 2000?mg/kg/day. Clinical observations including mortality, moribundity, behavioural changes, signs of overt toxicity, body weight, gross pathological changes of dams and foetal analyses including external malformations, skeletal and soft tissue malformations were evaluated. Results: No evidence of maternal or foetal toxicity was observed. WSR extract caused no changes (p?Discussion and conclusion: Under the conditions of the study, the no-observed-effect level (NOEL) of WSR extract for maternal and developmental toxicity was concluded to be at least 2000?mg/kg/day.     

One year oral Toxicity of D-004, a lipid extract from Roystonea regia fruits, in Sprague Dawley rats

D-004, a lipid extract of royal palm (Roystonea regia) fruits that contains a reproducible mixture of fatty acids, has been shown to prevent testosterone and phenylephrine-induced prostate hyperplasia in rodents. This study investigated the long-term oral toxicity of D-004 in rats. Rats from both sexes were randomized into four groups (20 rats sex/group): a control and three treated with D-004 (800, 1500 or 2000 mg/kg/day, respectively). At study completion, rats were sacrificed under anaesthesia. Determinations of blood biochemical and haematological parameters and organ weight were done. Also, necropsy and histopathological studies were performed. Four of 160 rats died before study completion. No clinical signs of toxicity were observed throughout the study. Food and water consumption, bodyweight, blood biochemical and haematological parameters, organ weight ratios and histopathological findings were similar in control and treated groups. The histological lesions found in treated animals are commonly present in this specie and strain according to literature and our historical data. In conclusion, long-term (12 months) oral treatment of rats with D-004 (800–2000 mg/kg/day) did not show evidences of D-004-related toxicity under our conditions. The highest dose tested (2000 mg/kg) was a no-observed adverse effect level in this study.     

28-day repeated dose oral toxicity of human copper-zinc superoxide dismutase from recombinant Pichia pastori in rats

Human copper/zinc superoxide dismutase from recombinant Pichia pastori (RH-Cu/Zn-SOD) was orally administered, via gavage, to Sprague-Dawley rats at 500, 1,000, and 2,000?mg/kg body weight/day for 28 days. During the 28-day period, animals were examined for evidence of toxicity; there were no deaths, and in-life physical signs were normal. On day 29, the animals were exsanguinated, examined for gross pathology, and tissues were preserved for histopathology. Although statistical differences were noted in some hematology and clinical chemistry, they were of questionable biological significance. The results of the 28-day oral administration demonstrated a lack of toxicity of RH-Cu/Zn-SOD in rats. There were no treatment-related, toxicologically relevant changes in clinical signs, growth, food consumption, hematology, clinical chemistry, organ weights, or pathology. The no observed adverse effect level was greater than 2,000?mg/kg/day for RH-Cu/Zn-SOD in rats.     

Acute and subacute (28-Day) toxicity studies of ionic liquid,didecyldimethyl ammonium acesulfamate,in rats

The aim of this study was to investigate acute and subacute oral toxicity of an ionic liquid, didecyldimethylammonium acesulfamate [DDA][Ace], in rats. The compound tested was classified to the fourth toxicity class with a fixed LD₅₀ cut-off value of 500?mg/kg. Organ pathology induced by [DDA][Ace] in acute experiments included exfoliation of the surface layer of the digestive tract and alveolar septa in lung parenchyma. In a subacute experiment, rats were administered 10, 50, and 100?mg/kg/day [DDA][Ace] for 28 days. Reduced body weight gain and reduced food consumption was observed in mid- and high-dose rats. Statistically significant hematology changes were found mostly in high-dose groups of both sexes: increases in hematocrit, mean corpuscular volume, and mean platelet volume. Statistically significant changes in clinical chemistry parameters included increases in the GGT, SDH, and LDH activity and bilirubin concentration, and decreases in triglycerides, glucose, and inorganic phosphorus concentration. No treatment-related microscopic changes were observed. Under the conditions of this study, the lowest-observed-adverse-effect level of [DDA][Ace] was considered to be 10?mg/kg/day.     

Single and 90-day repeated oral dose toxicity studies of fermented Rhus verniciflua stem bark extract in Sprague–Dawley rats

Fermented Rhus verniciflua stem bark (FRVSB) extract, an urushiol-free extract of Rhus verniciflua Stokes (RVS) fermented with Fomitella fraxinea, has various biological activities. The present study was carried out to investigate the potential toxicity of the FRVSB extract following single and repeated oral administration to Sprague–Dawley rats. In the single dose toxicity study, the FRVSB extract was administered orally to male and female rats at single doses of 0, 2500, 5000, and 10,000 mg/kg. No animals died and no toxic changes were observed in clinical signs, body weight, and necropsy findings during the 15-day period following administration. In the repeated dose toxicity study, the FRVSB extract was administered orally to male and female rats for 90 days at doses of 0, 556, 1667, and 5000 mg/kg/day. There were no treatment-related adverse effects in clinical signs, body weight, food and water consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, organ weight, and histopathology at any dose tested. The approximate lethal dose of the FRVSB extract was >10,000 mg/kg in both genders, the oral no-observed-adverse-effect level of the FRVSB extract was >5000 mg/kg/day in both genders, and no target organs were identified.     

Acute and developmental toxicity assessment of erincine A-enriched Hericium erinaceus mycelia in Sprague–Dawley rats

This study aimed to establish an in vitro model to confirm the efficacy of erinacine A-enriched Hericium erinaceus (EAHE) mycelia and investigate its potential adverse effects in a preclinical experimental setting, including an assessment on the oral administration of EAHE mycelia in acute and prenatal developmental toxicity tests. At a single dose of 5000?mg/kg body weight, EAHE mycelia elicited no death or treatment-related signs of toxicity in ten Sprague–Dawley rats of both sexes during the 14?days of the experimental period. After considering the recommended dose range of EAHE mycelia from the acute toxicity test as well as the therapeutic doses, EAHE mycelia was administered to 66 pregnant rats in the low, medium, and high-dose groups by gavage at 875, 1750, and 2625?mg/kg body weight, respectively. All dams were subjected to a Caesarean section on the 20th day of pregnancy, and the fetuses were examined for any morphological abnormalities. Results indicated that weight of uterus, fetal body weight, number of corpora lutea, implantation sites, pre-implantation loss, and post-implantation loss of the treatment groups and the control group exhibited no statistical difference. In addition, no significant differences were observed in the fetal external, organ, and skeletal examinations. Taken together, it can be concluded that EAHE mycelia is considered safe and practically nontoxic for consumption within the appropriate doses and investigation period in this study.     

毛叶疏花蔷薇果提取物的亚慢性毒性研究

目的考察毛叶疏花蔷薇果提取物的亚慢性毒性。方法选用96只健康SD大鼠随机分为4组,雌雄各半,分别ig给予0、1.25、2.50、5.00 g/kg毛叶疏花蔷薇果提取物,连续90 d,观察动物生长情况。试验中、末期对动物的血液学和血清生化指标进行检测,试验末计算动物主要脏器的脏器系数,并进行组织病理学检查。结果试验期间动物无死亡。试验末各剂量组动物体质量增长值、进食量、食物利用率、脏器质量、脏器系数与对照组比较差异均无统计学意义。在试验中、末期各剂量组动物血液学检测指标与对照组比较差异无统计学意义。血清生化检测发现,试验中期5.00 g/kg剂量组雌雄大鼠血清中的肌酐(CR)和雌性大鼠血清中的尿素氮(BUN)水平显著升高;末期5.00 g/kg剂量组雄性大鼠血清中的CR水平仍居高不下,与对照组比较差异均有统计学意义(P0.05、0.01),而其他指标均在正常值范围内。病理组织学检查发现5.00 g/kg剂量组部分动物肾小管和小肠可见相关病理改变。结论在本实验条件下,5.00 g/kg毛叶疏花蔷薇果提取物对SD大鼠的肾和小肠有损伤作用,最大无作用剂量为2.50 g/kg。     

Subchronic (90-day) toxicity assessment of Somacy-FP100, a lipopolysaccharide-containing fermented wheat flour extract from Pantoea agglomerans

Pantoea agglomerans is a Gram-negative bacterium that is ubiquitous in the environment, colonizing animals, humans, and numerous plants, including cotton and wheat. A lipopolysaccharide-containing fermented wheat flour extract from P. agglomerans (Somacy-FP100) is proposed for use as a food ingredient for individuals seeking foods for healthy aging. Previously published genotoxicity studies with Somacy-FP100 reported its lack of genotoxicity in vitro, but a subchronic toxicity study has not yet been performed. Therefore, to demonstrate the safety of Somacy-FP100 for use as a food ingredient, a 90-day oral (gavage) toxicity study in rats was conducted. Male and female Han Wistar rats were administered vehicle (control) or Somacy-FP100 at 500, 1500, or 4500 mg/kg body weight/day at a dose volume of 10 mL/kg body weight, for at least 90 days. No test article-related adverse clinical signs or effects on body weight, food consumption, or clinical pathology were observed, and there were no macroscopic or microscopic findings related to the test article. Therefore, 4500 mg/kg body weight/day (the highest dose tested and highest feasible dose) was established as the no-observed-adverse-effect level. This absence of subchronic toxicity, in addition to the previously reported lack of genotoxicity, demonstrates the safety of Somacy-FP100 for use as a food ingredient.     

Assessment of oral toxicity and safety of 9-cis-UAB30, a potential chemopreventive agent,in rat and dog studies

9-cis-UAB30 is a potential chemopreventative agent that has been shown to be effective on many different types of tumors. The safety and toxicity of 9-cis-UAB30 had not been previously established. These studies were conducted to evaluate the potential toxicity and pharmacokinetics in a rodent and a nonrodent species for the purpose of investigational new drug submission. Oral gavage administration of 9-cis-UAB30 at the doses 0, 3, 15, and 100?mg/kg/day to CD^® rats for 28 days showed a dose-dependent (although not dose-proportional) increase in plasma drug levels in week 4. The liver was the target organ for toxicity of 9-cis-UAB30. Hepatomegaly along with increases in serum aspartate-aminotransferase and alkaline-phosphatase levels were seen in rats. Moderate hypoalbuminemia and hyperglobulinemia resulted in a decreased albumin/globulin ratio. Histopathology revealed hepatocellular change consistent with hepatic glycogen deposition. Toxicity studies in dogs did not show treatment-related toxicity at doses as high as 100?mg/kg/day (highest dose tested) administered by capsules for 28 days. No effects on the central nervous system (functional observational battery in rats) or cardiovascular function (safety pharmacology study in telemeterized dogs) were seen. The no observed adverse effect level (NOAEL) in the rat studies was 3?mg/kg/day; however, the adverse effects seen in rats receiving 15?mg/kg/day (the least observed adverse effect level) was a slight, but statistically significant, elevation in fibrinogen and decrease in prothrombin time, which may be a sign of some tendency for increased blood coagulation. The NOAEL in the dog study was at least 100?mg/kg/day.     

Lack of Gender-Related Difference in the Toxicity of 2-(2′-Hydroxy-3′,5′-di-tert-butylphenyl)benzotriazole in Preweaning Rats

In our previous toxicity studies using young rats, we showed that an ultraviolet absorber, 2-(2′-hydroxy-3′,5′-di-tert-butylphenyl)benzotriazole (HDBB), principally affected the liver, and male rats had nearly 25 times higher susceptibility to the toxic effects than females. In the present study, the toxicity of HDBB was investigated in preweaning rats. HDBB was administered by gavage to male and female CD(SD) rats from postnatal days 4 to 21 at a dose of 0, 0.1, 0.5, 2.5, or 12.5 mg/kg/day. No substance-related deaths, clinical signs of toxicity, or body-weight changes were observed. Increased levels of albumin, AST and ALP in both sexes, BUN in males, and LDH in females were found at 12.5 mg/kg. Liver weights increased at 2.5 mg/kg and above in both sexes. Histopathologically, hepatocellular findings, such as nucleolar enlargement, anisokaryosis, increased mitosis, and/or hypertrophy, were observed at 2.5 mg/kg and above in both sexes. These results indicate no gender-related differences in the susceptibility to the toxic effects of HDBB in preweaning rats.     

Toxicological studies on aqueous extract of Gmelina arborea in rodents

Context:?Gmelina arborea Roxb. (Verbenaceae) is an important medicinal plant in the traditional system of medicine of India. The plant is used in the treatment of snake-bites, fever, piles, and diabetes. However, there is little toxicological information available regarding its safety after exposure. The present study was designed to evaluate acute and repeated dose toxicity of the aqueous extract of Gmelina arborea stem bark.

Materials and methods:?In the acute toxicity test, Swiss albino mice were treated with aqueous extract (300, 2000, and 5000?mg/kg), orally. Animals were observed periodically during the first 24?h after administration of the extract, and daily thereafter for 14 days. In the repeated dose toxicity study, the aqueous extract of Gmelina arborea (300, 1000, and 2000?mg/kg per day) was administered orally for a period of 28 days in Wistar rats. The effects on body weight, food and water consumption, organ weight, hematology, clinical biochemistry, as well as histology, were studied.

Results and conclusion:?Aqueous extract did not produce mortality, changes in behavior or any other physiological activities in mice, for any of the selected doses. There were no significant differences in the body weight, organ weights and feeding habits between control and treated animals. Hematological and biochemical analysis showed no marked differences in any of the parameters examined in either the control or treated groups. Pathologically, neither gross abnormalities nor histopathological changes were observed. The aqueous extract of Gmelina arborea was found safe in acute and repeated dose toxicity studies when tested in rodents.     

Acute oral toxicity of the ethyl acetate fraction of Orostachys japonicus in mice

Context: Orostachys japonicus (Crassulaceae) is referred to as Wa-song in Korea. It is used as an anti-inflammatory, antifebrile, hemostatic, and anti cancer agent, and as an antidote.

Objective: The purpose of this study was to evaluate the acute toxicity of the ethyl acetate fraction of O. japonicus (OJE) after the oral administration in Balb/c mice of both sexes.

Materials and methods: Mice were oral administered a single doses of 500, 1000, and 2000?mg/kg of body weight and were monitored for 14?d. Biochemical parameters [aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP), total protein (TP), globulin (GB), total cholesterol (TC), triglyceride (TG), blood urea nitrogen (BUN), and creatinine (CR)] and histopathological examination of liver were performed.

Results and conclusion: No animals died and no toxic changes were observed in clinical signs, body weight, and organ weight. The LD₅₀ of orally administered OJE was higher than 2000?mg/kg/d in both sexes. No toxicological findings were found in biochemical parameters. In histophathological examination, neutrophilic infiltration was observed at a dose of 2000?mg/kg group in both sexes. These finding suggest that oral administration of OJE does not produce acute toxicity. Therefore, these results could provide satisfactory preclinical evidence of safety to launch clinical trials on standardized formulation of OJE to be a biohealth product.     

Anticoagulant activity of isolated coumarins (suberosin and suberenol) and toxicity evaluation of Ferulago carduchorum in rats

Context: Ferulago carduchorum Boiss. &; Hausskn. (Apiaceae) is known as Chavil in Persian which grows in west of Iran. Local people add Chavil to dairy and oil ghee as a natural preservative to extend the expiration date.

Objective: The goal of this survey is the safety evaluation of the total extract of F. carduchorum in rats by determining both oral acute and subchronic toxicities; furthermore, the anticoagulant activity of isolated coumarins was evaluated.

Materials and methods: The aerial parts of F. carduchorum were extracted by the percolation method. The anticoagulant activity of isolated coumarins was evaluated and the total extract was used to investigate acute and subchronic toxicity in rats. In the subchronic toxicity model, doses of 250, 500, and 1000?mg/kg of the extract were administered to treated groups for 30?consecutive days by gavage.

Results: According to the results of acute toxicity, the LD₅₀ of Chavil extract was more than 2000?mg/kg. The subchronic study showed no significant difference (p?>?0.05) between the groups treated with extract and control groups in hematological (erythrocyte, total and differential leukocyte, hematocrit, hemoglobin, platelet count) and biochemical parameter (glucose, albumin, cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase) evaluations. The isolated coumarins (suberosin and suberenol) prolonged the prothrombin time (PT) at doses of 3 and 6?mg/kg compared with control (p?Conclusion: In conclusion, oral administration of the Chavil extract did not cause either acute or subchronic toxicities although the coumarins showed anticoagulant effect in rats.     

Ninety days of repeated gavage administration of Rhodiola imbricata extract in rats

Rhodiola imbricata is a high‐altitude plant, possesses adaptogenic, immunomodulatory, anti‐oxidant and cytoprotective activity, and is widely used in traditional medicine. The present study was designed to ascertain the safety of aqueous extract of R. imbricata root when administered by gavage to rats for 90 days. Four groups of animals, each consisting of 15 males and 15 females, were administered 0, 100, 250 or 500 mg kg^?1 extract, in a single dose per day. The experimental rats when administered 100 mg kg^?1 of extract did not show any significant change in their body weight gain, organ/body weight ratio, or histological, hematological and biochemical variables studied. However, at higher doses of 250 and 500 mg kg^?1 extract, an increase in the body weight of rats of both the sexes was apparent without any change in their organ/body weight ratio. Furthermore, a noteworthy increase in plasma glucose and protein levels was recorded at both the higher doses, which were restored to normal after a 2‐week withdrawal of treatment. Based on the findings of this study, the no observed effect level was 100 mg kg^?1 body weight per day of aqueous root extract of R. imbricata in rats administered subchronically. Copyright © 2011 John Wiley & Sons, Ltd.     

Safety studies conducted on high-purity trans-resveratrol in experimental animals

trans-Resveratrol is a naturally occurring polyphenolic compound found in a variety of foods, but predominantly in grapes. Safety studies were conducted on high-purity trans-resveratrol (Resvida™), including skin and eye irritation, dermal sensitization, subchronic and reproductive toxicity, genotoxicity, and absorption, metabolism and excretion. Resvida™ was non-irritating to skin and eyes and non-sensitizing. It was non-mutagenic in a bacterial reverse mutation assay in Salmonella typhimurium and Escherichia coli, but exhibited clastogenic activity in a chromosomal aberration test in human lymphocytes. However, in an in vivo bone marrow micronucleus test in rats, Resvida™ was non-genotoxic. In a 28-day study, Resvida™ caused no adverse effects in rats at 50, 150 and 500 mg/kg bw/day. Similarly, in a 90-day study, Resvida™ did not cause any adverse effects in rats at up to 700 mg/kg bw/day; the highest dose tested. Resvida™ did not induce any adverse reproductive effects in an embryo–fetal toxicity study in rats at a dose of 750 mg/kg bw/day. Also, in vitro and in vivo absorption, metabolism, and excretion studies in Caco-2 cells, rat primary hepatocytes and male and female rats (in vivo) show that Resvida™ is readily absorbed, metabolized and excreted. These studies provide evidence that Resvida™ is well tolerated and non-toxic.     

Comparison of protective and curative potential of Daucus carota root extract on renal ischemia reperfusion injury in rats

Abstract

Context: Daucus carota Linn (Apiaceae), a useful vegetable, is traditionally used in treating kidney and hepatic dysfunctions.

Objective: To evaluate the protective and curative potential of D. carota root extract on renal ischemia reperfusion injury in rats.

Materials and methods: Wistar rats were selected with 8?+?8 groups (n?=?6). Renal pedicles of rats were occluded for 45?min and allowed for reperfusion period. In protective and curative studies, 14 days prior and 14 days after the induction of ischemia/reperfusion (I/R), rats received petroleum ether extract (PEE 250 and 500?mg/kg), fractional methanol extract (FME 250 and 500?mg/kg) and direct methanol extract (DME 250 and 500?mg/kg) of Daucus carota root, orally, once daily.

Results: PEE at a dose of 500?mg/kg significantly (p?<?0.001) reduced the levels of serum creatinine (0.853–3.090?mg/dl), uric acid (1.300–3.500?mg/dl) and urea (58.26–132.00?mg/dl) compared to disease control. FME at a dose of 500?mg/kg body weight significantly (p?<?0.001) reduced the levels of serum creatinine (0.960–3.090?mg/dl), uric acid (1.700–3.500?mg/dl) and urea (77.17–132.00?mg/dl) compared to disease control. DME at a dose of 500?mg/kg body weight significantly (p?<?0.001) reduced the levels of serum creatinine (1.173–3.090?mg/dl), uric acid (2.267–3.500?mg/dl) and urea (84.75–132.00?mg/dl) compared to disease control.

Discussion and conclusion: Findings demonstrate that postconditioning with the D. carota root extract significantly improves kidney function in I/R rats.     

Himematsutake (Iwade Strain 101) extract (ABM-FD): Genetic toxicology and a 3-month dietary toxicity study in rats

Agaricus blazei Murrill, an edible mushroom, is used as a functional food due to medicinal effects of (1→6)-β-D-glucan protein complex which has been shown to have anti tumour activity in mice. A 13 week oral subchronic study in rats performed at 500, 1000 or 2000 mg/kg/day caused, at the highest dose, reduced erythrocyte numbers and high mean cell volume in males, high creatinine and urea concentrations in both sexes and low spleen weights in females, but no histopathological change. The findings suggested low level chronic toxicity at 2000 mg/kg/day and a no observed adverse effect level (NOAEL) of 1000 mg/kg/day. Genotoxicity tests on the aqueous extract were negative in the bacterial reverse mutation test, either with or without S9 mix, up to 5000 μg/plate and in a rat bone marrow micronucleus test up to 2 g/kg bodyweight. The extract was positive at acceptable levels of toxicity in an L5178Y mouse lymphoma assay following 24 h exposure in the absence of S9 and this was associated with an increase in the number of small colonies, suggesting possible clastogenic activity or aneuploidy, rather than point mutation. The aqueous extract of A. blazei is therefore of low subchronic toxicity and did not cause any direct effect upon the DNA molecule and the weak positive in the L5178 mouse lymphoma test was likely due to large deletions or the loss of the whole chromosomes rather than to direct damage to the DNA.