General Behavior Adverse Effects Research Articles

Acute and Subacute Toxicity Studies of the Aqueous Extract from Haloxylon scoparium Pomel (Hammada scoparia (Pomel)) by Oral Administration in Rodents.

Materials and Methods Acute toxicity test was performed on Swiss albino mice at a single oral dose of 1-10 g/kg for 14 consecutive days. General behavioral adverse effects, mortality, and latency of mortality were determined. In the subacute study, the Haloxylon scoparium Pomel extract was administered orally at doses of 500, 1000, and 2000 mg/kg daily for 30 days to Wistar rats. Body weight and selected biochemical and hematological parameters were determined at the end of the experiment. Sections of livers and kidneys were removed for histological studies. Results Acute toxicity study showed that the oral LD50 value of Haloxylon scoparium Pomel extract was 5000 mg/kg. The subacute toxicity study of Haloxylon scoparium Pomel extract at doses 500, 1000, and 2000 mg/kg did not produce any observable symptoms of toxicity and no significant variation in body weight, organ weights, food, and water consumption or mortality in all treated rats. However, the administration of the Haloxylon scoparium Pomel extract to rats at 500 mg/kg and 1000 mg/kg showed a significant decrease in platelets. Moreover, only at the highest dose (2000 mg/kg), the extract caused a significant increase in red blood cells and hemoglobin. Our results showed that subacute treatments with Haloxylon scoparium Pomel extract at doses of 1000 mg/kg and 2000 mg/kg significantly elevated alkaline phosphatase and triglycerides. Histological studies showed that the subacute treatments of rats with Haloxylon scoparium Pomel extracts, at the doses 1000 and 2000 mg/kg, induced some histopathological changes in the livers but a slight changing in kidneys. Conclusion Our results indicated low acute toxicity of the aqueous extract of Haloxylon scoparium Pomel. Furthermore, daily oral administration of Haloxylon scoparium Pomel extract caused some damages to the livers of rats treated with high doses, expressed by an increase in some enzyme activities such as ALP. Regarding the renal function, we did not find remarkable toxicity in the subacute treatment with Haloxylon scoparium Pomel extracts at doses 1000 and 2000 mg/kg. However, further toxicity assessments should be done to ascertain the safety or the toxicity of this valuable plant species “Haloxylon scoparium pomel” in subchronic treatments.

English

Camellia hakodae Ninh (CHN) is an ornamental plant of Vietnam, whose extracts is used as a potential phytotherapeutic beverage due to its good improvement in the immune system, reduction of inflammation and assisting the treatment of some chronic diseases. CHN production may be useful for health during this coronavirus epidemic period. This study aimed to evaluate the safety, acute and sub-chronic toxicity of aqueous extracts of CHN leaf in mice. In the acute toxicity study, CHN leaf at doses from 24.0 to 120.0 g/kg/day was given to 5 groups of Swiss mice by oral administration (equivalent in humans is 0.2 to 10 g/kg/day). Mice were observed for general behavioral changes, adverse effects and mortality up to 7 days post-treatment to find the highest dose that did not kill mice (the dose of death 0% (LD0)), the lowest dose that completely killed the mice (the dose of death 100% (LD100)) and the intermediate doses (LD50). In sub-chronic toxicity studies, CHN was given orally to 2 groups of Wistar rats at doses of 2.8 and 14 g CHN/kg/day (equivalent in humans is 0.4 and 2 g/kg) for 28 days taking CHN daily. After 28 days of taking CHN, mice were operated to observe the whole organ for histopathology. The microscopic structure of the liver, spleen, and kidney of at least 30% of mice in each group was randomly checked. The acute toxicity study in all the doses used did not cause any significant change as no LD50 was found. In addition, the sub-chronic toxicity study did not show any treatment-related abnormalities with regard to hematological and biochemical parameters. These results demonstrated that the CHN leaf aqueous extract is safe and does not appear to exert toxicity. Key words: Camellia hakodae Ninh, golden tea, acute and sub-chronic administration, Vietnamese tea. &nbsp

Acute and Sub-acute Toxic Effects of Algerian Peganum harmala L. Crud Extract

The present study was carried out to evaluate the acute and sub-acute toxicity of Algerian Peganum harmala L. seeds (Zygophyllaceae). For the acute toxicity assessment, oral administration of P. harmala crud extract to mice in single doses of 0-12 g/kg caused dose-dependent general behavior adverse effects and mortality with LD50 of 2,86 g/kg. In the sub-acute study, daily oral administration of the crude aqueous extract for 28 consecutive days did not result no mortality. However, our results showed a significant difference in organs weights between control and treated animals. In the biochemical analysis, significant changes occurred in Bilirubin, uric acid (UA) and alkaline phosphatase (ALP) in the treated animals when compared to the control ones. Hematological analysis showed differences in WBC count and Hemoglobin estimation. However, urinalysis was negative for all parameters except Glucose in the treated group. Pathologically, a few gross abnormalities and histological changes were observed in hepatic and nephritic tissues.
 Keywords: Peganum harmala L., Acute and Sub-Acute Toxicity, Hematological parameters, Biochemical parameters

Phytochemical screening, acute and sub-acute toxicity of aqueous extract from a mixture of some recipe of Herniaria glabra L., Opuntia ficus-indica, Zea mays L. and Zizyphus lotus L. used traditionally against renal lithiases

Introduction: Antiurolithiatic plants are used since ancient times, in the form of decoction, infusion, or juice, to eliminate kidney stones and to prevent their recurrence. On the basis of the available ethnopharmacological information, more scientific studies are needed to explore natural and safe antiurolithiatic compounds. Materials and Methods: The present work showed phytochemical screening, acute and sub-acute toxicity of aqueous extract of four plant's mixture: Aerial part (branches, flowers and leaves) of Herniaria glabra, flowers of Opuntia ficus-indica, Zea mays styles and fruits of Zizyphus lotus used traditionally against renal lithiases. Phytochemical screening was performed using qualitative methods. To measure acute toxicity, rats were administered orally by single doses of 0.1, 0.2, 0.5 and 2.0 g/kg body weight (b. w.) of extract of plant's mixture. General behavior adverse effects and mortality were determined during 15 days. For sub-acute study, the aqueous extract was administered at 100 mg/kg b. w. for 28 days to Wistar rats. Animals were monitored daily after an oral administration of aqueous extract of the mixture to detect any changes in b. w., behavior, autonomic profiles, or mortality. Calculation of relative organ weight (ROW) and biochemical analysis were carried out. Results: The acute oral toxicity study showed no mortality and no statistically significant decrease in b. w. and ROW of the treated groups of rats when compared to the control group was observed. In biochemical analysis, there was a significant increase in aspartate aminotransferase, creatinine, urea, and uric acid. Conclusion: This study found that aqueous extract of traditional recipe used against renal lithiasis in Fes-Meknes region containing: Flavonoids, tannins, catechic tannins, coumarins and the glycosides. The results of the acute and sub-acute toxicity studies indicated that the recipe extracts induce a slight hepatotoxic effects in rats treated orally with 100 mg/kg (b. w.).

Studies of acute and subchronic systemic toxicity associated with a copper/low-density polyethylene nanocomposite intrauterine device.

IntroductionThe physiologic safety of devices and materials intended for clinical implantation should be evaluated. This study, a logical extension of our previous work, aimed to investigate the safety of a novel contraceptive device, the copper/low-density polyethylene nanocomposite intrauterine device (nano-Cu/LDPE IUD), through studies of its potential toxicity after acute and subchronic administration in mice and rats.MethodsFor the acute toxicity study, single 50 mL/kg doses of nano-Cu/LDPE IUD extracts were administered to mice via intravenous or intraperitoneal injection. General behavioral adverse effects, mortality, and body weights were evaluated for up to 72 hours. In the 13-week subchronic toxicity study, the nano-Cu/LDPE composite with 10-fold higher than the standard clinical dose was implanted subcutaneously into the dorsal skin of Wistar rats. The control group underwent a sham procedure without material insertion.ResultsDuring all acute study observation times, the biologic reactions of the mice in the nano-Cu/LDPE group did not differ from those observed in the control group. The groups did not differ statistically in terms of body weight gain, and no macroscopic changes were observed in any organs. In the subchronic study, no clinical signs of toxicity or mortality were observed in either the nano-Cu/LDPE or control group during the 13-week period. The nano-Cu/LDPE composite did not cause any alterations in body weight, food consumption, hematologic and biochemical parameters, or organ weight relative to the control for any observed sample group. Histopathologic examinations of the organs revealed normal architecture, indicating that the inserted material did not cause morphologic disturbances in the rats.ConclusionOverall, the results indicate that the nano-Cu/LDPE IUD did not induce systemic toxicity under experimental conditions of the recommended standard practices, suggesting that the novel material IUD is safe and feasible for future contraceptive applications.

Study the Acute & Sub Acute Toxicity of Ricinus cummunis Lnn. Ethanol Extract of Seed in Albino Mice

Background: Toxicity still a global problem for the environment, agriculture and ultimately human health.
 Objective: In this study attempt to investigate the toxicological profile of the ethanol, extract of Ricinus cummunis after acute and sub-chronic administration to mice.
 Methods: In the acute toxicity study, a single administration of the extract at doses of 1000,2000,3000,4000 and 5000 mg/kg, respectively, was gave orally. Mice were observed for general behavioral changes, adverse effects and mortality up to 10 days post-treatment. In sub-acute toxicity studies, herbal extract was gave orally to mice at doses of 50 mg/kg, 100 mg/kg and 150 mg/kg for 10 days.
 Results: In the acute toxicity study, the mortality appeared in 2000 mg/kg and LD50 were calculated at 1100 mg/kg. In the sub-chronic toxicity the study show significant differences in body weight between the control and treated groups (p < 0.05). Histopathology of vital organ (liver & kidney) show morphological changes.
 Conclusions: These results demonstrate the real toxic effect of the ethanolic extract after single dose. The LD50 value is 1100 mg/kg and research indicates that successive use of the seed at the dose above (2 g/kg in human) daily for long period may cause toxic signs.
 Highlights: The Ricinus communis oil's has wide variety of industrial applications: as a drying oil for paints, varnishes, plastics and resins is an ingredient in numerous cosmetics. But it need to toxicity study as acute and sub-acute with observation of hematological and histopathological to be more safety for used.

Acute and sub-acute oral toxicity studies of the aqueous extract from radix, radix with cortex and cortex of Psammosilene tunicoides in mice and rats

Ethnopharmacological relevancePsammosilene tunicoides is one of the important ingredients of a famous Chinese traditional medicine formulation “Yunnan Baiyao”. Also, this plant is commonly used as an anodyne and hemostatic agent in southwest China. Currently, little toxicological information is available on its safety following prolonged use. Aim of the studyIn this study, we sought to evaluate the toxicity of the three different parts of Psammosilene tunicoides: Psammosilenes Radix (PR), Psammosilenes Radix with Cortex (PRC) and Psammosilenes Cortex (PC) by acute and sub-acute toxicity studies. Materials and methodsIn the acute toxicity study, mice were orally administrated with different doses of PR, PRC and PC. General behavior and mortality were observed up to 14 days. In sub-acute toxicity study, these aqueous extracts were given orally as a single administration to rats at doses of 0.3, 0.6 and 1.2g/kg/day, respectively, for 28 days. General behavior, body weight, biochemical, hematological, organ coefficients and pathological morphology parameters were detected. ResultsIn acute study, single oral administration of the aqueous extract of PR, PRC and PC caused dose-dependent general behavior adverse effects and mortality. The LD50 values of PR, PRC and PC were 4.64g/kg, 4.85g/kg and 6.40g/kg, respectively. In sub-acute study, the administration of the extract of PR, PRC and PC during 28 days at all doses reduced spontaneous activities with both genders. Occasional nasal secretion with blood at high doses (1.2g/kg) of PR, PRC and PC were observed. Daily single oral administration provoked varying degrees of growth retardation in female rats. The relative heart and spleen weight in the female rats were reduced after the administration. On the hematological and biochemical analyses, the administration of the extract of PR, PRC and PC during 28 days mainly caused variation of indexes in female rats. Histopathological analysis has shown vascular congestion in heart, thickened alveolar wall and emphysema in lung, and vascular congestion in kidney of rats after sub-acute oral administrations. ConclusionsAs shown in the results, Psammosilene tunicoides has a toxic potential in acute and sub-acute oral administrations. However, there is no direct relationship between toxicity and the cortex. Daily oral administration of three different parts from Psammosilene tunicoides (PR, PRC and PC) may cause damages to heart, lung and kidney in rats. Thus these extracts should be used with caution.

Toxicological study of the butanol fractionated root extract of Asparagus africanus Lam., on some blood parameter and histopathology of liver and kidney in mice.

BackgroundThe butanol fractionated root extract of Asparagus africanus Lam., a traditional herb widely used to treat various ailments were analyzed for the presence of potential toxicity after single (acute) and repeated (subchronic) dose oral administration in adult swiss albino mice using gavages.MethodsFor the acute study, butanol fractionated extract of the plant was administered in single doses of 1000, 3000 and 5000 mg/kg body weight. In the sub-chronic dose study, the extract was administered at doses of 300 and 600 mg/kg body weight/day for 42 days. Selected hematological and biochemical parameters of the blood followed by histopathological analysis were investigated after 42 days of daily administrations. The results were expressed as M ± SE, and differences at P < 0.05 was considered significant. One way analysis of variance (ANOVA) and least significant difference tests were employed to check the significant differences between the various parameters of the experimental groups.ResultsIn the acute study, the extract did not caused dose-dependent general behavioral adverse effects, body weight change and mortality. The single dose toxicity studies therefore showed that the butanol fraction of the extract has high safety profile when given orally. After 42 days of daily dosing, in the sub-chronic study, no clinically significant changes were observed for hematological and biochemical parameters. Except an occasional small number of focal mononuclear lymphocytic cells infiltrations around the central and portal triad of the liver of a few mice, the histopathological parameters do not show significant change.ConclusionIt is concluded that, the butanol fractionated extract from A. africanus at the given dose does not show significant toxicity. The presence of focal inflammation on the liver of a few mice may be associated to the presence of flavonoid glycoside in the butanol fractionated extract.

Acute and sub-chronic oral toxicity profiles of the aqueous extract of Cortex Dictamni in mice and rats

Ethnopharmacological relevanceCortex Dictamni is used in Chinese folk medicine for the treatment of jaundice, cough, rheumatism and some skin diseases; however, its possible toxicity has not been rigorously studied. The present investigation was carried out to evaluate the safety of Cortex Dictamni aqueous extract (CDAE) by acute and sub-chronic toxicity studies. Materials and methodsIn acute toxicity tests, seven groups of mice (n=5/group/sex) were orally treated with doses of 0, 28.7, 33.6, 39.7, 46.7, 54.9 and 64.6g/kg of CDAE and general behavior, adverse effects and mortality were recorded for up to 14 days. In sub-chronic toxicity assays, animals received CDAE by gavage at the doses of 0, 3.0, 6.0 or 12.0g/kg/day (n=10/group/sex) for 4 weeks and then followed for a 2-week recovery period. The biochemical, hematological and morphological parameters were determined. ResultsIn adult mice, single oral administrations of CDAE (0–64.6g/kg body weight) induced an increase in the incidence of general behavioral adverse effects. The mortality rate also increased with increasing dosage (LD50=48.2g/kg). In rats, daily single oral doses of CDAE were well tolerated behaviorally after 4 weeks and induced no significant changes in body weights. However, the absolute and relative liver weight at the end of both administration and recovery periods were significantly elevated, although the histological examination of various organs revealed no differences between the control and the treated groups. The hematological and biochemical parameters were significantly changed; lymphocytes, alanine transaminase, alkaline phosphatase levels showed a significant decrease while neutrophilic granulocyte, albumin, total cholesterol, glucose and blood urea nitrogen levels showed a significant increase, suggesting disturbances of hematopoiesis and liver and kidney functions. ConclusionsOverall, the acute toxicity of CDAE was not clearly observed. However, it is possible that CDAE has a selective toxicity considering the changes in some hematological and liver function parameters and the liver-body weight ratios in the sub-chronic oral toxicity study.

Acute oral toxicity and liver oxidant/antioxidant stress of halogenated benzene, phenol, and diphenyl ether in mice: a comparative and mechanism exploration

The lethal doses (LD50s) of fluorinated, chlorinated, brominated, and iodinated benzene, phenol, and diphenyl ether in mice were ascertained respectively under the consistent condition. The acute toxicity of four benzenes orders in fluorobenzene (FB) < iodobenzene < chlorobenzene≈bromobenzene, that of four phenols orders in 4-iodophenol≈4-bromophenol < 4-chlorophenol (4-MCP) < 4-fluorophenol (4-MFP), and that of four diphenyl ethers orders in 4,4'-iododiphenyl ether < 4,4'-difluorodiphenyl ether < 4,4'-dichlorodiphenyl ether≈4,4'-dibromodiphenyl ether. General behavior adverse effects were observed, and poisoned mouse were dissected to observe visceral lesions. FB, 4-MCP, and 4-MFP produced toxic faster than other halogenated benzenes and phenols, as they had lower octanol-water partition coefficients. Pathological changes in liver and liver/kidney weight changes were also observed. Hepatic superoxide dismutase, catalase activities, and malondialdehyde level were tested after a 28-day exposure, which reflects a toxicity order basically consistent with that reflected by the LD50s. By theoretical calculation and building models, the toxicity of benzene, phenol, and diphenyl ether were influenced by different structural properties.

Pre-clinical toxicity of Morinda citrifolia Linn. leaf extract

This investigation was carried out to evaluate the safety of an aqueous extract of Morinda citrifolia leaves (AEMC) by determining its potential toxicity after acute administration (5 g/kg) in rodents and cytotoxic studies. General behavior adverse effects and mortality were determined for up to 14 days. Biochemical and hematological parameters were determined after 14 days. Cytotoxic effects of the AEMC were determined by spectrophotometric 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay (at concentration of 0.05 to 25 mg/ml). The results showed that in the acute study in rats, the AEMC did not cause general behavior adverse effects and mortality. Also, AEMC did not show any cytotoxic effect at 0.05 to 12.5 mg/ml, only at 25 mg/ml. The AEMC does not appear to have significant toxicity. Key words: Morinda citrifolia, cytotoxicity, acute toxicity.

Evaluation of acute toxicity of babassu mesocarp in mice

The safety of babassu mesocarp (Orbignya phalerata Mart., Arecaceae), which exhibited anti-inflammatory and antithrombotic activities, was evaluated by determining the potential acute toxicity in mice. A lyophilized ethanol extract of babassu mesocarp (BME) was administered to C3H/HePas mice (10/group) in a single dose of 1000, 3000 and 5000 mg/kg, by gavage. General behavior adverse effects and mortality were determined for up to fourteen days. Selected biochemical parameters including glucose, triacylglyceride, cholesterol, urea, alkaline phosphatase and creatinine were determined by colorimetric assay. The heart, liver, spleen, kidneys and brain were weighted and evaluated macro and microscopically. The median lethal dose (LD50) of BME was greater than 5000 mg/kg. No behavior or body weight alterations were detected after the treatment. The acute treatment with BME has no effect on macroscopic and microscopic aspect of examined organs. Instead, BME increased the alkaline phosphatase and reduced the urea concentration in all groups. A significant increase on triacylglyceride was detected in the group BME1000. In conclusion, the acute treatment with high doses of BME can affect some biochemical parameters with a long lasting effect, although any change was detected at tissue level or body and organ weight.

Acute and subacute toxicological evaluation of scutellarin in rodents

Acute and subacute investigations were carried out to evaluate the safety of scutellarin, an active flavone glycoside that has been used to treating cardiocerebral vascular diseases and cerebral infarction in rodents. For the acute study, scutellarin was administered to mice by gavage at different dose levels. Scutellarin caused dose-dependent general behavior adverse effects, but the LD 50 values could not be detected, and the maximum tolerated dose was more than 10 g/kg. In the subacute study, scutellarin was administered orally at doses of 100 and 500 mg/kg daily for 30 days to rats. Body weight, heart rate, blood pressure, biochemical, hematological and urine parameters were determined at the end of the experimental day. Daily oral administration for up to 30 days did not result in death or significant changes in hematology, blood chemistries or urinalysis. However, a 30 day regimen of scutellarin at doses of 100 or 500 mg/kg led to non-dose related decreases in BUN and triglyceride levels. Scutellarin was found to be minimally toxic or non-toxic in rodents. In view of the doses of the components used, the results from acute and subacute toxicity studies suggest that this component has a sufficient margin of safety for therapeutic use.

Acute and sub-chronic toxicity of a lyophilised aqueous extract of Centaurium erythraea in rodents

An aqueous concoction made from centaury (Centaurium erythraea (L.) Rafn., (Gentianaceae) whole plant is used in the Moroccan traditional medicine for the treatment of diabetes, as well as a number of other diseases. No systematic study of the potential toxicity of the plant has been described. The present investigation was carried out to evaluate the safety of an aqueous extract of Centaurium erythraea whole plant (CE-extract) by determining its potential toxicity after acute and sub-chronic administration in rats and mice. For the acute study, the lyophilised CE-extract was administered to adult IOPS OFA mice in single oral doses of 1-15 g/kg given by gavage, and single intraperitoneal (i.p.) doses of 1-14 g/kg. General behavioral adverse effects, mortality, and latency of mortality were determined for up to 14 days. In the sub-chronic dose study, the CE-extract was administered orally at doses of 100, 600 and 1200 mg/kg daily for 90 days to Wistar rats. Body weight and selected biochemical and hematological parameters were determined every 30 days and at the end of 90 days of daily administration; sections of liver and kidney were examined histologically for any signs of organ damage at the end of the treatment. In the acute study in mice, there were no deaths or any signs of toxicity observed after oral administration of single doses of the CE-extract at any dose level up to the highest dose tested (15 g/kg), which was the no-observed-adverse-effect level (NOAEL). However, the mortality rate as well as the acute toxicity of the i.p. administered CE-extract increased progressively with increasing dose. The NOAEL for the i.p. dose was 6 g/kg while the lowest-observed-adverse-effect level (LOAEL) was 8 g/kg; the calculated acute toxicity (LD(50)) of i.p. administered CE-extract in mice was 12.13 g/kg. In sub-chronic studies in rats, the CE-extract (administered orally at daily doses of 100, 600 and 1200 mg/kg for 90 days), did not cause any changes in hematological and biochemical parameters, except a small reduction of mean corpuscular volume, and a decrease in serum glucose and triglyceride levels at the higher doses. Histopathological examination of the liver and kidneys at the end of the study showed normal architecture suggesting no morphological disturbances. Because of the lack of toxicity of the CE-extract given by the oral route, and relatively high NOAEL values for the i.p. dose in the acute study in mice, as well as lack of mortality or clinically significant adverse changes in the biological and hematological parameters, and the morphology of liver and kidneys in rats after 90 days of daily dosing, it may be concluded that the CE-extract is relatively non-toxic. Also, in view of the doses consumed empirically in traditional medicine in Morocco, there is a wide margin of safety for the therapeutic use of Centaurium erythraea.

Acute and subacute toxicity of ethanol extracts from Salvia przewalskii Maxim in rodents

Aim The present investigation was carried out to evaluate the safety of the lipid-soluble ethanol extracts from rhizome of Salvia przewalskii Maxim (SPM) by determining its potential toxicity after acute and subacute administration in rodents. Materials and methods For the acute study, SPM extract was administered to mice in single doses given by gavage, intramuscular and intraperitoneal route. General behavior adverse effects and mortality were determined for up to 14 days. In the subacute study, the extract was administered orally at doses of 0, 50 and 250 mg/kg daily for 30 days to rats. Body weight, heart rate, blood pressure, biochemical and hematological parameters were determined at the end of 0, 15 and 30 days of daily administration. Results In acute study, SPM extract caused dose-dependent general behavior adverse effects and mortality. The no-observed adverse effect levels (NOAEL) of the extract were 1723, 288 and 500 mg/kg, when given by gavage, intramuscular and intraperitoneal routes, respectively, and the lowest-observed adverse effect levels (LOAEL) were 1981, 840 and 781 mg/kg. Mortality increased with increasing doses, with LD 50 of 2547.8, 901.3 and 780.8 mg/kg for the oral, intramuscular and intraperitonal administration. In subacute study, daily oral administration of SPM extract for up to 30 days did not result in death or significant changes in the body weight, heart rate and blood pressure, hematological and mainly biological parameters. In biological analysis, some significant changes occurred, including total protein and albumin, glucose and triglycerides, indicating that SPM extract has lipid-modulating activity. Conclusions SPM extract was found to be low or non-toxic when acute toxicities and subacute toxicities in rodents. In view of the doses of the components consumed in traditional medicine, there is a wide margin of safety for the therapeutic use.

Acute toxicity and sub-chronic toxicity of steroidal saponins from Dioscorea zingiberensis C.H.Wright in rodents

Ethnopharmacological relevance Steroidal saponins from Dioscorea zingiberensis are widely used in China for curing cardiovascular diseases. However, there was little toxicological information available on them. Aim of the study The study evaluated potential toxicity of the steroidal saponins and analyzed the metabolites in rats. Materials and methods For the acute study, the steroidal saponins were administered to kunming mice in single doses of 112.5–9000 mg/kg given by gavage. General behavior adverse effects, mortality and liver histopathological changes were examined. For the sub-chronic toxicity study, Sprague–Dawley rats were gavaged at doses of 127.5, 255 and 510 mg/kg/day for 30 days, then examined the biochemical and hematological parameters. Metabolites in serum were analyzed by HPLC–MS. Results The steroidal saponins caused dose-dependent general behavior adverse effects, mortality and liver histopathological changes in the acute toxicity study. In the sub-chronic toxicity study, 510 mg/kg/day of steroidal saponins increased total bilirubin (TBIL) in serum and decreased protein content in liver significantly. The metabolic process of TBIL in liver includes TBIL intaking, conjugated bilirubin forming, conjugated bilirubin excreting to biliary passage. Treatment with high dose of the steroidal saponins in vivo may lead to vacuolization of the cytoplasm of hepatocytes and canalicular cholestasis. In all doses used in the experiment, the steroidal saponins decreased aspartate aminotransferase (GOT), alanine aminotransferase (ALT) and alkaline phosphatase (AKP) in serum and increased reduced glutathione hormone (GSH), glutathione reductase (GR) and glutathione S-transferases (GST) in liver. Diosgenin was the main metabolite in serum. Conclusions The steroidal saponins did not show any sign of toxicity up to oral dose of 562.5 mg/kg in mice. No significant changes of biochemical and hematological parameters in rats (except at 510 mg/kg/day), it was concluded that the steroidal saponins did not appear to have significant toxicity in their traditional uses.

Acute and subchronic toxicity of danshensu in mice and rats

Danshensu (3-(3,4-dihydroxyphenyl) lactic acid), a natural phenolic acid, is isolated from Salvia miltiorrhiza root, and is the most widely used traditional Chinese medicine for the treatment of various cardiovascular diseases. It has been reported to have potential protective effects from oxidative injury. However, there is a little information about its possible toxicity. In this study, acute and subchronic toxicity of danshensu in mice and rats have been evaluated. In the acute study, danshensu intraveniouslly administered to rats failed to induce any signs of toxicity or mortality up to a maximum practical dosage of 1500 mg/kg body weight. Test substance administered acutely to mice caused dose-dependent general behavior adverse effects and mortality with the medial lethal dose of 2356.33 mg/kg. The no observed adverse effect level and the lowest observed adverse effect level were 1835 mg/kg and 2000 mg/kg, respectively. In the subchronic study, rats were tested by daily intraperitoneal injection of danshensu at the doses of 50, 150, and 450 mg/kg for 90 days, resulting in no mortality, no changes in body weight, food consumption, hematological and serum chemistry parameters, organ weights, or gross pathology or histopathology. The only treatment-related finding was transient writhing response observed in the 450 mg/kg group after administration.

Acute and sub-chronic toxicity of an aqueous extract of the leaves of Herniaria glabra in rodents

Aim of the study The present investigation was carried out to evaluate the safety of an aqueous extract of Herniaria glabra (caryophyllaceae) (HG) plant by determining its potential toxicity after acute and sub-chronic administration in rodents. Materials and Methods For the acute study, a lyophilized aqueous extract of HG plant was administered to adult IOPS OFA mice in single doses of 5–14.5 g/kg given by gavage. General behavior adverse effects and mortality were determined for up to 14 days. In the sub-chronic dose study, the HG-extract was administered orally at doses of 1, 2 and 4 g/kg daily for 90 days to Wistar rats. Selected biochemical and hematological parameters were determined after 30 and 60 days, and then at the end of 90 days of daily administration. Results In the acute study in mice, the crude aqueous extract of HG plant caused dose-dependent general behavior adverse effects and mortality. The no-observed adverse effect levels (NOAEL) of the HG extract was 5 g/kg and the lowest-observed adverse effect levels (LOAEL) was 5.5 g/kg. Mortality increased with increasing doses: the calculated LD 50 was 8.50 + 0.42 g/kg in mice. In the sub-chronic study in rats, daily oral administration of the crude HG extract for up to 90 days resulted in a significant attenuation of the normal increase in the body weight. At the highest dose, the HG-extract caused a significant increase in erythrocytes, leukocytes (WBC), platelets, and eosinophils, but it had no effect on the differential WBC counts (lymphocytes, monocytes, neutrophils and basophils). Only at the highest dose, the HG-extract caused a significant increase in serum levels of the liver enzymes, alanine aminotransferase and aspartate aminotransferase, as well as serum creatinine, indicating toxic effect of the high dose of the extract on the liver and kidney. The organ toxicity was confirmed by histopathological examination, which showed centrolobular sinusoidal congestion, disruption of the central vein and hepatocellular necrosis in the liver, and interstitial and intraglomerular congestion, tubular atrophy, and inflammation in the kidney. This study also revealed the hypoglycemic activity of the HG-extract in normoglycemic rats. The suppression of the normal weight gain and the hypoglycemic action of HG-extract should be investigated further for possible therapeutic implications. Conclusions Because of the relatively high NOAEL values in the acute study in mice, and lack of mortality or clinically significant changes in the biological (except for hypoglycemia) and hematological parameters in rats after 90 days of daily dosing, it may be concluded that the HG extract does not appear to have significant toxicity (except at high doses). In view of the doses consumed empirically in traditional medicine in Morocco, there is a wide margin of safety for the therapeutic use of Herniaria glabra.

Acute and chronic toxicity of a lyophilised aqueous extract of Tanacetum vulgare leaves in rodents

Aim of the study The present investigation was carried out to evaluate the safety of an aqueous extract of tansy (Tanacetum vulgare L.) leaves by determining its potential toxicity after acute and chronic administration in rodents. Materials and Methods For the acute study, a lyophilized aqueous extract of tansy leaves was administered to mice in single doses of 0-13 g/kg given by gavage as well as intraperitoneal doses of 0–4.5 g/kg. General behavior adverse effects and mortality were determined for up to 14 days. In the chronic dose study, the extract was administered orally at doses of 0, 100, 300 and 600 mg/kg daily for 90 days to rats. Biochemical and hematological parameters were determined after 30 and 60 days, and then at the end of 90 days of daily administration. Results In the acute study in mice, the crude aqueous extract of tansy leaves caused dose-dependent general behavior adverse effects and mortality. The no-observed adverse effect levels (NOAEL) of the tansy extract were 7.0 g/kg and 1.0 g/kg, and the lowest-observed adverse effect levels (LOAEL) were 9.0 g/kg and 1.5 g/kg, when given by the oral and intraperitoneal routes, respectively. Mortality increased with increasing doses, with LD 50 of 9.9 g/kg and 2.8 g/kg for the oral and intraperitonal modes of administration, respectively. In the chronic study in rats, daily oral administration of the crude aqueous extract of tansy leaves for up to 90 days did not result in death or significant changes in the biological (except for hypoglycemia) and hematological parameters. Conclusions Because of the relatively high NOAEL values in the acute study in mice, and lack of significant effect on biological and hematological parameters in rats after 90 days of daily doses, the tansy extract does not appear to have significant toxicity. In view of the dose of tansy consumed in traditional medicine, there is a wide margin of safety for the therapeutic use of the aqueous extract of Tanacetum vulgare leaves.