Metabonomics study of liver and kidney subacute toxicity induced by garidi-5 in rats / 中草药·英文版

Objective: Metabonomics was used to analyze and explore the biomarkers and possible mechanisms of liver and kidney subacute toxicity induced by garidi-5 in rats. Methods: Taking garidi-5 as the target drug and SD rats as the research objects, each administration group except the normal group was intragastric administration of the corresponding drug solution for 28 d. The serum, liver and kidney samples of rats were detected by metabolomics and characterized by principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) to identify the sensitive markers and metabolic pathways of liver and kidney subacute toxicity. Results: Metabolomics analysis showed that compared with the normal group (Z), the 52, 64 and 54 different metabolites were identified in the serum, liver and kidney samples of garidi-5 high dose group (GG), which were mainly enriched in ABC transporters, arginine and proline metabolism, nicotinate and nicotinamide metabolism, central carbon metabolism in cancer pathways. Conclusion: The preliminarily suggested that garidi-5 can damage the liver and kidney by affecting the ABC transporters, arginine and proline metabolism, nicotinate and nicotinamide metabolism pathways, etc. Trimethylamine N-oxide, L-pyroglutamic acid, glycine-betaine, xanthine, glutathione, L-leucine, cytidine, L-arginine, spermidine, urea, 5-aminovaleric acid, creatine, L-glutamic acid, 1-methylnicotinamide and S-adenosyl-L-methionine can be used as potential biomarkers of liver and kidney toxicity sensitivity.

Toxicity of the Hydroethanolic Leaves Extract of Duranta erecta L. in Rat Models

Background and Objectives:Duranta erectais used in folklore medicine for the treatment of myriad of diseases in Africa. The study was carried out to evaluate the safety of hydroethanolic leaves extract of D. erectain experimental rats in order to ascertain its potential toxic effects. Materials and Methods:The acute toxicity study was performed by fixed dose method at 5000 mg/kg. In the subacute study performed on both male and female rats, group I (control) received 1 mL of freshly distilled water, groups II, III, IV were treated with 100, 250 and 500 mg/kg of freshly prepared extract respectively for 28 days. At the end of the study, haematological and biochemical parameters were determined. Internal organs (kidney, liver, lung, heart, spleen, stomach, testes and uterus) were weighed.Results:50% lethal dose (LD50) of the extract was determined to be >5 g/kg body weight. The subacute toxicity assessment resulted in overall body weight increase, a change in relative organ weight of the liver, lung, stomach, and changes in the haematological indices such as HCT%, LYM%, RDW-SD/fL, MCHC, MCV/fL, P-LCR% and biochemical parameters namely ALT, AST, LDH and creatinine of the tested group relative to the normal. The positive activity of the extract on liver enzymes and LDH is an indication of its good hepatoprotective potential.Conclusion:The results affirmed that the extract is safe but could cause kidney problems when used for a prolonged period

Toxicity evaluation of water extract of tissue-cultured Taraxacum formosanum by acute, subacute administration, and Ames test

BACKGROUND: Taraxacum species (commonly known as dandelion) used as herbal medicine have been reported to exhibit an antiproliferative effect on hepatoma cells and antitumor activity in non-small-cell lung cancer cells. Although several investigations have demonstrated the safety of Taraxacum officinale, the safety of tissue-cultured plants of T. formosanum has not been assessed so far. Therefore, the present study examines the safety of the water extract of the entire plant of tissue cultured T. formosanum based on acute and subacute toxicity tests in rats, as well as the Ames tests. RESULTS: No death or toxicity symptoms were observed in the acute and subacute tests. The results of the acute test revealed that the LD50 (50% of lethal dose) value of the T. formosanum water extract for rats exceeded 5 g/kg bw. No abnormal changes in the body weight, weekly food consumption, organ weight, or hematological, biochemical, and morphological parameters were observed in the subacute toxicity test. Thus, the no observed adverse effect level (NOAEL) of T. formosanum water extract was estimated to be higher than 2.0 g/kg. Finally, the results of the Ames test revealed that T. formosanum water extract was not genotoxic at any tested concentration to any of five Salmonella strains. CONCLUSIONS: The water extract of tissue-cultured T. formosanum was non-toxic to rats in acute and subacute tests and exhibited no genotoxicity to five Salmonella strains.

Acute and subacute toxicity evaluation of hydroalcoholic extract of Caryota urens leaves in Wistar rats

Caryota urens native to Srilanka and India grows in tropical and subtropical regions. It is rich in nutrition andshow pharmacological properties owing to the presence of flavonoids, coumarins, carbohydrates, and amino acids.However, scientific reports which guarantee the safety of C. urens are not available. Therefore, the intention of thecurrent investigation was to assess the potential toxicity of the hydroalcoholic extract of C. urens leaves (CULHA)in Wistar rats. In acute toxicity study, CULHA was administered at a single oral dose of 2,000 mg/kg body weight.In subacute toxicity study, CULHA was administered once a day at three dose levels of 100, 200, and 400 mg/kg body weight for 28 days. At the end of the treatment, animals were sacrificed; vital organs were removed andexamined histopathologically. Blood and serum samples were collected and processed immediately for the analysis ofhematological and biochemical parameters. During acute toxicity study, treatment-associated death or manifestationof toxic clinical symptoms were not seen. Furthermore, results of both acute and subacute toxicity group exposed toCULHA did not exhibit significant change in hematology, biochemical parameters, and histopathology. The resultsdemonstrated that CULHA did not possess potential to induce toxicity

Subacute toxicity study of an aqueous extract of dried leaves of Gymnosporia spinosa on albino rats

Background: Leaves of Gymnosporia spinosa have been used by people for treatment of jaundice. Traditional herbal drugs are popular all over the world and it is presumed that herbal medicines have lesser or no side effects. This generalized belief and no information available regarding toxicity study of G. spinosa with search from limited available information prompted us to carry out work on subacute toxicity study of aqueous extract of dried leaves of G. spinosa.Methods: Subacute toxicity study was carried out using aqueous extract of G. spinosa leaves. 30 rats of either sex were randomly divided in to 4 groups. First group received distilled water (control). Second, third and fourth groups received single daily dose of drug orally as 40, 120 and 240 mg/100 g of body weight respectively for 3 weeks. Animals were observed for various parameters. After 21 days blood was collected for blood counts and biochemical parameters. Liver, lungs and kidney were subjected to histo-pathological studies.Results: Throughout study there was no mortality in any group. Degenerative changes in the liver. Other organ does not show any changes. Analysis of biochemical data showed serum glutamic pyruvic transaminase and s. alkaline phosphatase levels were decreased. Serum bilirubine, blood urea and serum creatinine level were increased significantly.Conclusions: The data showed that there was hepato-renal toxicity at higher dose level which is about 100x human therapeutic dose.

Evaluation of antioxidant capacity and reproductive toxicity of aqueous extract of Thai Mucuna pruriens seeds / 中西医结合学报

OBJECTIVE@#In traditional medicine, the seeds of Thai Mucuna pruriens (T-MP) are used to treat male dysuria and are believed to enhance fertility. However, information pertaining to the toxicity of T-MP and its interaction with other properties is limited. This study was thus conducted to evaluate the antioxidant capacity and subacute toxicity of T-MP in the reproductive system.@*METHODS@#Total phenolic content and antioxidant capacity of T-MP seed extract were determined using total phenolic content, 2,2-diphenyl-1-picrylhydrazyl and ferric reducing antioxidant power assays. Male and female adult rats were treated orally with T-MP at a dosage of 150 or 300 mg/kg body weight for 14 consecutive days. Sex hormones and functional parameters in the liver and kidney were evaluated. Histopathology of all tissue was conducted using Masson's trichrome staining. Sperm parameters, including concentration, morphology, acrosome reaction status and DNA damage, were also examined. Expression of tyrosine phosphorylated protein (TyrPho), androgen receptor and A-kinase-anchoring protein 4 (AKAP4) were investigated using the Western blot technique.@*RESULTS@#T-MP seed extract contained phenolic compounds and exhibited high antioxidant capacity with no toxicity at the tested doses. It did not affect liver or kidney function parameters in the male rats, but increased estradiol, aspartate aminotransferase and alanine aminotransferase levels in the females. Additionally, it decreased serum progesterone and alkaline phosphatase levels in female rats. Serum and intratesticular testosterone levels were significantly lower in male rats that received a high dosage of T-MP. Histopathological changes were not observed in any tissue treated with T-MP. T-MP also significantly increased sperm concentration (but did not affect sperm parameters), and enhanced testicular TyrPho protein and androgen receptor and expression of AKAP4 in sperms.@*CONCLUSION@#T-MP seed extract exhibited antioxidant capacity and was not harmful to reproductive tissues. It also had a phytoestrogenic effect on females and increased the expression of testicular and sperm markers of male fertility.

Nauclea latifolia (Rubiaceae) Stem-bark Hydromethanolic Extract Abrogates a Histone Deacetylase Inhibitor - Induced Multifocal Toxicity in Albino Rats

Objective: Nauclea latifolia (Rubiaceae) stem-bark enjoys wide patronage in ethnomedicine due to multiplicity of usage. Acute and subacute hematological and biochemical toxicity studies are available in literature but none underpins its ameliorative effect with a histone deacetylase inhibitor (HDAC), valproic acid (VPA) which mediates multifocal toxicity in different histological milieu. Methods: Subacute exposure of experimental albino rats with a high dose of valproic acid (500 mg/kg) was executed orally one hour before post-treatment with Nauclea latifolia stem-bark (NLS) extract in three doses (50, 100, 200 mg/kg) and with another group of rats with reference drug, vinpocetine, 25 mg/kg daily for 28 consecutive days after which hematological and biochemical analyses were executed. The liver, kidney and lungs were abstracted for histopathological evaluation. Results: The HDAC inhibitor, Valproic acids induced multifocal biochemical insults on liver function enzymes, lipid profiles, electrolytes and kidney function which were dose- dependently and significantly (P < 0.05 – 0.001) abrogated by the varying doses of administered NLS extract. On the histology the NLS extract effects corroborated the biochemical study in the liver and kidney. The NLS did not demonstrate significant toxicological impingement on the hematology and did not alter VPA-induced histomorphological injury in the lungs cytoarchitecture. The reference drug, vinpocetine was unresponsive to VPA-induced alteration in all the tissues investigated in the administered posology. Conclusion: The NLS extract was effective in abrogating toxicological insults in the liver and kidney but not in the lungs. Further studies are required to understand the mechanism of pharmacological effects of NLS extract and the differential in tissue response.

1H NMR-based nontargeted metabonomics study of plasma and urinary biochemical changes in Kudouzi treated rats

Abstract Kudouzi (Sophora alopecuroides L., Fabaceae) is an effective folk medicine, but it always causes a hepatic and renal toxicity in clinical therapy. The toxic mechanism remains unclear. This paper detected the urinary and plasma metabolites alteration by 1H NMR-based metabonomics study in Kudouzi-induced rats to evaluate the toxic mechanism for clinical security. The male Sprague-Dawley rats were orally dosed with 0.5 and 1 g Kudouzi/kg weight once per day for consecutive 14 days. Urine samples were collected at day −1 (before treatment), and days 7, 14, and 21 for NMR analysis, respectively. Plasma samples were harvested at day 14 for NMR and biochemical analysis. The metabonomic profiling of Kudouzi-treated rats differed from that of the vehicle. This was confirmed by the biochemistry analysis. The accumulated subacute toxicity of Kudouzi was visible with dosing time, and persisted at day 21 even after the disposal was ended. The observable biochemical pathways alterations included inhibited TCA cycle, activated anaerobic glycolysis, perturbed amino acids metabolism, and disordered gut microbiota. The results evidenced the toxicity mechanism of Kudouzi from a systematic and holistic view.

Evaluation of acute and subacute toxicity of whole-plant aqueous extract of Vernonia mespilifolia Less. in Wistar rats / 中西医结合学报

<p><b>OBJECTIVE</b>This study investigated the acute and subacute toxicity of whole-plant aqueous extract of Vernonia mespilifolia Less. (AEVM) in rats for evaluating its safety profile.</p><p><b>METHODS</b>AEVM for the acute (2000 and 5000 mg/kg) and subacute (200, 400 and 600 mg/kg) toxicity studies was administered orally to rats according the guidelines 425 and 407 of Organization for Economic Cooperation and Development, respectively. Food and water intake as well as body and organ weight of animals were recorded. Signs of toxicity were assessed, and hematological, biochemical and histopathological analyses were performed.</p><p><b>RESULTS</b>In the acute toxicity study, a single dose of the aqueous extract at 2000 or 5000 mg/kg caused no mortality in the animals, suggesting that the median lethal dose is greater than 5000 mg/kg. In the subacute toxicity study, administration of the extract for 28 d, at all doses, caused no significant changes in the body weights or organ weights of rats in the treated groups when compared with the control group. In addition, hematological and biochemical parameters also revealed no toxic effects of the extract on rats. Histological sections of the heart, liver and kidney from test animals showed no signs of degeneration.</p><p><b>CONCLUSION</b>These results showed that AEVM at dosage levels up to 600 mg/kg is nontoxic and could also offer protection on some body tissues. AEVM could, therefore, be considered safe.</p>

Cardiotoxicity and neurotoxicity features of Aconiti Radix ethanol extract and its impacts on vascular endothelial / 中草药

Objective: To investigate the features of cardiotoxicity and neurotoxicity and the influence on vascular endothelial of ethanol extract of Aconiti Radix (AR). Methods: Totally 45 Wistar rats were randomly divided into four groups, and ig given low-, middle-, and high-dose 70% ethanol extract of AR (in the raw drug dose of 2.5, 5.0, and 7.5 g/kg respectively) for 15 d. The toxic reaction and death condition were observed during administration. The electrocardiogram (ECG) change was tested after administration. Blood was collected for blood routine and blood biochemistry analysis. Brain was harvested for calculating viscera index and pathological examination. Left ventricular and hippocampus were extracted and stained with electron microscope (EM) methods. Results: At the end of treatment, all rats were sacrificed in the high-dose AR group. The mortality and hematologic parameters including RBC, HGB, HCT, ALT, UREA, and GLU were significantly increased in the middle-dose AR groups compared with control group. Arrhythmia especially ventricular arrhythmia occurred in low- and middle-dose AR group. Brain index and number of pyknotic neurons in focal area of hippocampus were significantly increased in middle-dose AR group. EM examination indicated that dissolution of neuronal inclusions, nuclear fragmentation, and coagulation necrosis of glial cells were prominent in the hippocampus tissue in middle-dose AR group. In the middle-dose AR group, the vascular endothelial cells injury and apoptosis were obviously observed in left ventricular and hippocampus separately. Conclusion: The ethanol extract of AR can lead to cardiotoxicity and neurotoxicity especially vascular endothelial injury in dose-dependent manner.

Toxicological Study of a Siddha Sastric Formulation Arumuga Chendhuram in Rat Model.

The study was aimed to profile the acute and sub-acute oral toxicity of a herbo-metallic drug Arumuga Chendhuram (AC). AC was prepared classically and analyzed for elemental composition using X-ray Fluorescence. Acute oral toxicity study was done on female rats at AC 2 g/kg as single administration following OECD guideline 423. For sub acute toxicity study, AC was administered orally for 28 consecutive days suspended in vehicle (Honey + distilled water) to rats following OECD guideline 407. Four groups was allotted (10 rats/group), control received vehicle; the other received AC at 12, 24 & 48 mg/kg/day respectively. Mortality and abnormal clinical signs were observed. Haematological and biochemical parameters were analyzed using auto analyzer with standard kits and ANOVA-Dunnett test was performed for significant analyses. Gross necropsy and histopathology studies using H&E stain were done on major organs. Mercury and Lead were found more than the WHO permissible limits in XRF study. LD50 was found more than 2 g/kg. No-Observed-Adverse-Effect level of AC was seen at 24 mg/kg in 28 days of treatment. No abnormal findings were noted in high dose group organs. Administration of AC at its human therapeutic dose of 260 mg/kg in rat (24 mg/kg) is safe.

Acute and Sub-acute oral toxicity studies of Deedan-A Unani drug in Albino rats.

Deedan is a very effective compound formulation of Unani System of medicine used for the treatment of worm infestation. The objective of this study was to investigate the Acute and Sub-acute toxicity of Deedan in Albino rats of both the sexes. In the acute toxicity study, Deedan was administered orally at the limit dose of 2000mg/kg b.w. to both male and female rats, and the animals were then observed individually 30 minutes, 4 hour postdosing, and at least twice daily for next 14 days. In the Sub-acute toxicity study a limit dose of 1000 mg/kg body weight was administered orally in a single bolus everyday for 28 days. The rats were observed daily during the period of study, and sacrificed on the 29th day. Observation parameters of the animals included a comparative evaluation of general appearance/behaviour, morbidity/mortality, body weights, food/water consumption, haematology, biochemistry and histopathology of major organs of treated and control groups. There was no mortality, morbidity, or cage-side/laboratory findings of any adverse health effect in the treated animals in comparison to their respective controls in both toxicity studies. Deedan was thus found to be free of any toxic effects under the conditions of these studies.

Evaluation of 2-week repeated oral dose toxicity of 100 nm zinc oxide nanoparticles in rats / 한국실험동물학회지

The aim of this study was to verify subacute oral dose toxicity of positively charged 100 nm zinc oxide (ZnO(AE100[+])) nanoparticles (NPs) in Sprague-Dawley rats. ZnO(AE100[+]) NPs were administered to rats of each sex by gavage at 0, 500, 1,000, and 2,000 mg/kg/day for 14 days. During the study period, clinical signs, mortality, body weight, food consumption, hematology, serum biochemistry, gross pathology, organ weight, and histopathology were examined. Increased mortality and clinical signs, decreased body weight, feed consumption, hemoglobin (HB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet (PT), and lymphocyte (LYM) and increased white blood cells (WBCs), neutrophils (NEUs), alkaline phosphatase (ALP), and histopathological alterations in the spleen, stomach, and pancreas were observed at 2,000 mg/kg/day. Increased clinical signs, decreased body weight, feed consumption, HB, HCT, MCV, MCH, MCHC, and LYM and increased WBCs, NEUs, ALP, and histopathological alterations in the spleen, stomach, and pancreas were seen at 1,000 mg/kg/day. Increased clinical signs, decreased MCV and MCH and increased histopathological alterations in the stomach and pancreas were found at 500 mg/kg/day. These results suggest that the target organs were the spleen, stomach, and pancreas in rats. The no-observed-adverse-effect level was <500 mg/kg for both sexes.

Investigation on the Acute and Subacute Toxicity of Alhagi Graecorum in Experimental Animals.

Little is known about the acute and subacute toxicity of Alhagi Graecorum (Camel Thorn) in mice. The aim of this study is to investigate the acute toxicity (LD50) and sub acute toxicity of camel thorn in mice. For determination of LD50, mice weighing 25-30 g were divided into nine groups each of 6 animals and received 130, 330, 660, 1300, 2600, 4200, 5000, 5900 and 6900 mg/kg orally of camel thorn water extract respectively. The sign and symptoms of toxicity and the number of died animals in each group were registered and the LD50 was calculated.Another group of Male albino mice weighed 25-30 g were divided into control and different treated group each of 6 mice and placed in the metabolism cages that allowed daily measurement of food and water consumption. The control received normal saline whereas the other groups received 130, 660, 1300 mg/kg (i.p, daily) of camel thorn extract (CTE)respectively, for two weeks.. The animals were weighed daily for any sign of reduction or gain of body weight. The food and water consumption were daily calculated. At the end of this experiment, the mice were killed and blood was collected and used for the determination of glucose and the serum creatinine,urea, aspartate, aminotransferase, (AST) and alanine aminotransferase (ALT) levels.The liver of the animals were removed,fixed in 10%formaline for histopathological investigation. The LD50 was equal to 5400mg/kg.Results of sub acute toxicity studies revealed that no significant weight reduction were observed in treated groups as compared to control, however the food consumption was significantly increased in the mice received 660mg/kg of CTE . Also the water consumption was significantly decreased in the animal receiving 1300mg/kg of CTE.

Hepatoprotective effect of acetone semicarbazone on Ehrlich ascites carcinoma induced carcinogenesis in experimental mice

Objective:To determine the hepatoprotective effect of acetone semicarbazone (ASC) in vivo in normal and Ehrlich ascites carcinoma (EAC) bearing male Swiss albino mice. Methods:Drug-induced changes in biochemical and behavioral parameters at dose of 2.0 mg/kg body weight for 14 d and nullifying the toxicity induced by EAC cells were studied. The histopathology studies of the protective effects of ASC on vital organs were also assessed. Results:The administration of ASC made insignificant changes in body weight and behavioral (salivation, diarrhea, muscular numbness) changes during treatment period due to minor toxicity were minimized after the treatment in normal mice. The biochemical parameters, including serum glutamate pyruvate transaminase, glutamate oxaloactate transaminase, alkaline phosphatase, serum glucose, cholesterol, urea, triglyceride and billirubin changed modestly in normal mice receiving ASC. Though the treatment continued, these values gradually decreased to normal level after the treatment. In EAC bearing mice, the toxic effects due to EAC cells in all cases were nullified by treatment with the ASC. Significant abnormalities were not detected in histology of the various organs of the normal mice treated with ASC. Conclusions: ASC can, therefore, be considered safe in formulating novel anticancer drug, as it exhibits strong protective effect against EAC cell bearing mice.

Hepatoprotective effect of acetone semicarbazone on Ehrlich ascites carcinoma induced carcinogenesis in experimental mice

<p><b>OBJECTIVE</b>To determine the hepatoprotective effect of acetone semicarbazone (ASC) in vivo in normal and Ehrlich ascites carcinoma (EAC) bearing male Swiss albino mice.</p><p><b>METHODS</b>Drug-induced changes in biochemical and behavioral parameters at dose of 2.0 mg/kg body weight for 14 d and nullifying the toxicity induced by EAC cells were studied. The histopathology studies of the protective effects of ASC on vital organs were also assessed.</p><p><b>RESULTS</b>The administration of ASC made insignificant changes in body weight and behavioral (salivation, diarrhea, muscular numbness) changes during treatment period due to minor toxicity were minimized after the treatment in normal mice. The biochemical parameters, including serum glutamate pyruvate transaminase, glutamate oxaloactate transaminase, alkaline phosphatase, serum glucose, cholesterol, urea, triglyceride and billirubin changed modestly in normal mice receiving ASC. Though the treatment continued, these values gradually decreased to normal level after the treatment. In EAC bearing mice, the toxic effects due to EAC cells in all cases were nullified by treatment with the ASC. Significant abnormalities were not detected in histology of the various organs of the normal mice treated with ASC.</p><p><b>CONCLUSIONS</b>ASC can, therefore, be considered safe in formulating novel anticancer drug, as it exhibits strong protective effect against EAC cell bearing mice.</p>

4-Week repeated oral dose toxicity study of 1,4-dichlorobutane in rats / 한국실험동물학회지

The present study investigated the potential subacute toxicity of 1,4-dichlorobutane by a 4-week repeated oral dose in Sprague-Dawley rats. The test article was administered once daily by gavage to male rats at dose levels of 0, 100, 300, and 1,000 mg/kg/day for 4 weeks. All rats were sacrificed at the end of the treatment period. During the test period, clinical signs, mortality, body weight, hematology, serum biochemistry, gross findings, and organ weight were examined. At 1,000 mg/kg/day, an increase in the clinical signs and weights of the liver and kidneys was observed in the male rats. Serum biochemical investigations revealed an increase in alanine aminotransferase, alkaline phosphatase, total cholesterol, total bilirubin, phospholipids, blood urea nitrogen, and gamma glutamyl transferase levels. There were no treatment-related adverse effects in the low and middle-dose groups. In the present experimental conditions, the target organs were determined to be liver and kidney. The no-observed-adverse-effect level was considered to be 300 mg/kg/day in rats.

Acute and subacute toxicity (28 days) of a mixture of ursolic acid and oleanolic acid obtained from Bouvardia ternifolia in mice / Toxicidad aguda y subaguda (28 días) en ratones, de la mezcla de ácido ursólico y ácido oleanólico obtenida de Bouvardia ternifolia

Ursolic acid (UA) and oleanolic acid (OA) are triterpenes that are found in a large number of medicinal plants, one of which is the species Bouvardia ternifolia. These compounds have been shown to have around 120 types of biological activity, especially the hepatoprotective, anti-inflammatory and antimycobacterial effects. Despite having a high therapeutic potential, not much information concerning their toxicity is available. This article describes the results of acute and subacute (28 days) toxicity evaluations in Balb/c mice (both sexes) treated with the mixture of UA/OA obtained from B. ternifolia at doses of 6.5 and 13 mg/kg. The LD50 was >300 mg/kg. During the subacute administration, there was no death of animals and no changes were observed in the growth or weight of the different organs when compared to the control groups. Studies of blood chemistry and blood count showed normal levels in all parameters evaluated. The histopathology of major organs showed no changes or abnormalities. The mixture UA/OA is indeed safe when administered subcutaneously as a single dose of 300 mg/kg or in repeated doses of 13 mg/kg during 28 days.

Los ácidos ursólico (UA) y oleanólico (OA) son triterpenos que se encuentran distribuidos en un gran número de plantas medicinales, una de ellas es la especie Bouvardia ternifolia. Estos compuestos han mostrado alrededor de 120 actividades biológicas, destacando los efectos hepatoprotector, antiinflamatorio y antimicobacteriano. A pesar de ser compuestos con un alto potencial terapéutico, no se han documentado muchos datos acerca de su toxicidad. En este artículo se describen los resultados de la evaluación de toxicidad aguda y subaguda (28 días) en ratones Balb/c de ambos sexos, tratados con la mezcla de AU/AO obtenida de B. ternifolia a dosis de 6.5 y 13 mg/kg. La DL50 fue > 300 mg/kg. Durante la administración subaguda, no hubo muerte de animales, tampoco se observaron alteraciones en su crecimiento ni alteraciones en el peso de los diferentes órganos. Los estudios de biometría hemática y química sanguínea mostraron niveles normales en todos los parámetros evaluados. Los análisis histopatológicos de los principales órganos no presentaron cambios o anormalidades. La mezcla UA/OA es prácticamente inocua cuando se administra subcutáneamente en dosis única de 300 mg/kg y 13 mg/kg en dosis repetida (28 días).

Toxicity studies of crude extracts from marine Streptomyces sps. with potential antibacterial sensitivity against antibiotic resistant human pathogens

Objective: To investigate the crude extract of marine actinomycetes with adverse effect locally on the adult Wister albino rats or systematically in the blood circulation. Methods: Acute toxicity, sub acute toxicity, biochemical and histopathological were tested. Results: In the results acute toxicity (LD50=2 500 μg/kg bw), sub acute toxicity study (2 500 μg/kg bw) were significant at 5% level of each experimental groups compared to the control group. Biochemical and histopathological study also showed better as compared with control group Conclusion:This crude microbial extract from Streptomyces sp. RSAUT 20 and Streptomyces scabiei (S. scabiei) RSAUK 49 is potential source for novel antimicrobial compounds. The crude extract of Streptomyces sp. RSAUT 20 and S. scabiei RSAUK 49 were tested for in vivo toxicity study.