Acute and sub-acute toxicity study of a Pakistani polyherbal formulation.
Ontology highlight
ABSTRACT:
SUBMITTER: Ishtiaq S
PROVIDER: S-EPMC5545041 | biostudies-other | 2017 Aug
REPOSITORIES: biostudies-other
Similar Datasets
Project description:BackgroundThe possible toxicity of natural products must be tested before being used in the market. The present work aimed to evaluate acute, subacute, and subchronic toxicity of an herbal formulation containing Anethum graveolens, Cynara scolymus, Citrus aurantium, Portulaca oleracea, and Silybum marianum.Material and methodsAcute toxicity (2000 mg/kg, single dose) and sub-acute toxicity (600 and 1200 mg/kg/day, 4 weeks) tests were performed on female and male rats according to OECD 423 and OECD 407 guidelines, respectively. In the subchronic study (12 weeks), the animals were divided into three groups (6 females and 6 males per group): control, low-dose group (food supplemented with 300 mg/kg of the herbal product), and high-dose group (600 mg/kg).ResultsThe herbal product at a single dose of 2000 mg/kg did not induce mortality for 14 days. In the sub-acute study, administration of the product for 28 days at 1200 mg/kg/day had no effect on survival, appetite (water and food consumption), body weight, serum biochemical parameters (BUN, creatinine, AST, ALT, ALP, bilirubin, albumin), histology of vital organs (liver, kidney, heart, brain), and hematological markers related to erythrocyte, platelet, and leukocyte. Similarly, in the subchronic study, the product did not induce mortality, change in histology of the vital organs, or alteration in hematological or biochemical parameters (except for an increase in ALP in female rats received 600 mg/kg).ConclusionThe formulated product shows no signs of toxicity in rats up to 2000 mg/kg, 1200 mg/kg, and 600 mg/kg in acute, subacute, and subchronic phases, respectively. It is suggested to monitor ALP levels in females in case of long-term use of the product.
| S-EPMC10692756 | biostudies-literature
Project description:BACKGROUND:Echinops kebericho is widely used for treatment of a variety of diseases including infectious, non-infectious disease and fumigation during child birth. Antibacterial, antimalarial, anti-leshimania, anti-diarrheal and insect repellent activities have been elucidated. Its toxicity profile is not yet investigated and thus this study was to investigate acute and sub-acute toxicity of E. kebericho decoctions. METHODS:Acute toxicity study was performed in female Wistar albino rats with single oral dose and followed up to 14 days. The sub-acute oral dose toxicity studies were conducted in rats of both sexes in accordance with the repeated dose 28-day oral toxicity study in rodent OECD guidelines. Physical observations were made regularly during the study period while body weight was measured weekly. Organ weight, histopathology, clinical chemistry and hematology data were collected on the 29th day. Results were presented as mean ± standard deviation. One-way analysis of variance (ANOVA) was performed if assumptions were met; otherwise Kruskal-Wallis analysis was performed. RESULT:Oral administration of E. kebericho decoction showed no treatment-related mortality in female rats up to the dose of 5000 mg/kg. In sub-acute toxicity studies, no significant treatment-related abnormalities were observed compared to negative controls. Food consumption, body weight, organ weight, hematology, clinical chemistry, and histopathology did not show significant variation between controls and treatment groups. However, creatinine, relative lung weight, triglycerides, and monocytes were lower in treated compared to control groups. Significant variations between male and female groups in food consumption, relative organ weight, hematology, clinical chemistry were observed. Histolo-pathology of high-dose treated groups showed fatty liver. CONCLUSION:Echinops kebericho showed LD50 of greater than 5000 mg/kg in acute toxicity study and is well tolerated up to the dose of 600 mg/kg body weight in sub-acute toxicity study.
| S-EPMC7076833 | biostudies-literature
Project description:IntroductionShigellosis is an intestinal disease and is one of the main causes of morbidity and mortality among children in India. The study aims to analyze the effect of the designed formulation on the hematological parameters in shigellosis-induced rats and assess the in vivo toxicity of this formulation.MethodsMale Wistar rats were housed in different groups. Group 1 is normal control; group 2 is diseased control; group 3 and group 4 diseased rats received 250 mg/kg formulation and 20 mg/kg body weight norfloxacin, respectively, orally once a day. Shigellosis was induced by a single intraperitoneal injection of Shigella flexneri, and bacterial load was calculated using the Shigella agar plate. On completion of the study, blood was collected for hematological as well as electrolyte analysis.ResultsThe in vivo acute toxicity results indicate that the formulation is safe up to 2000 mg/kg. Furthermore, formulation significantly (p < 0.05) decreases the bacterial load and increases the RBC, WBC, MCHC, platelet, hemoglobin, and electrolytes (Ca++, K+, and Na+) compared to diseased control.ConclusionThe results support the designed formulation's safety and therapeutic effects and support its use as an alternative medicine for treating shigellosis.
| S-EPMC10105236 | biostudies-literature
Project description:BackgroundBoesenbergia rotunda (fingerroot) rhizome extract contains two major bioactive components, panduratin A and pinostrobin. In our previous study, we found the anti-inflammatory effects of the fingerroot extract against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in golden Syrian hamsters. In the present study, we evaluated the sub-chronic toxicity of a fingerroot extract formulation over 90 consecutive days of oral administration.MethodsWe enhanced the water solubility of a fingerroot extract by formulating it with cyclodextrin, containing panduratin A (29% w/w) and pinostrobin (32% w/w). This formulation was administered to male and female Wistar rats at doses of 25, 50, or 100 mg/kg/day for a duration of 90 days. Additionally, two recovery groups, comprising a control group and a high-dose group, were designated for a 14-day observation period to assess the persistence and reversibility of potential adverse effects. Throughout the experiment, we performed clinical and health observations, followed by hematological testing, clinical biochemistry analysis, necropsy examination, and histopathological evaluation at the end of the experiment.ResultsThe administration of the fingerroot extract formulation at doses of 25, 50, or 100 mg/kg/day did not result in mortality or clinical signs of toxicity. No clinically significant findings were associated with the oral administration of the fingerroot extract formulation.ConclusionThe fingerroot extract formulation showed no serious adverse effects at doses up to 100 mg/kg/day in Wistar rats under the experimental condition. Consequently, the No Observed Adverse Effect Level (NOAEL) was considered to be 100 mg/kg/day. This finding contributes significance for future developments involving fingerroot extract in herbal medicinal products targeting chronic inflammation.
| S-EPMC10847838 | biostudies-literature
Project description:ContextThe leaves of Cajanus cajan (L.) Millsp. (Fabaceae) have diverse bioactivities, but little safety data are reported.ObjectiveThis study examines the toxicological profiles of C. cajan leaf extracts.Materials and methodsThe leaves were extracted by water or 90% ethanol to obtain water or ethanol extract (WEC or EEC). EEC was suspended in water and successively fractionated into dichloroform and n-butanol extracts (DEC and BEC). Marker compounds of the extracts were monitored by high-performance liquid chromatography (HPLC). Kunming mice were administered with a single maximum acceptable oral dose (15.0?g/kg for WEC, EEC and BEC and 11.3?g/kg for DEC) to determine death rate or maximal tolerated doses (MTDs). In sub-chronic toxicity investigation, Sprague-Dawley rats were orally given WEC or EEC at 1.5, 3.0 or 6.0?g/kg doses for four weeks and observed for two weeks after dosing to determine toxicological symptoms, histopathology, biochemistry and haematology.ResultsFlavonoids and stilbenes in the extracts were assayed. In acute toxicity test, no mortality and noted alterations in weight and behavioural abnormality were observed, and the maximum oral doses were estimated as MTDs. In sub-chronic toxicity study, no mortality and significant variances in haematological and biochemical parameters or organ histopathology were observed, but increased kidney weight in 3.0?g/kg WEC- or 3.0 and 6.0?g/kg EEC-treated female rats, and reduced testes and epididymis weight in EEC-treated male rats were recorded. These changes returned to the level of control after recovery period.ConclusionAcute and sub-chronic toxicity of Cajanus cajan leaf extracts was not observed.
| S-EPMC6130582 | biostudies-literature
Project description:Background: Jaranol has shown a wide range of pharmacological activities; however, no study has yet examined in vivo toxicity. The study aimed to investigate the oral acute and sub-acute toxicity of jaranol in mice. Methods: The acute toxicity was determined by a single oral dose of jaranol (2000 mg/kg). Therein animal behaviour and mortality rate were observed for 14 days. The jaranol (50, 100 and 200 mg/kg BW·d-1) was given by gavage for 28 days daily in the sub-acute study. The mouse body weight (BW), organ weight, food, water intake, biochemical, haematological parameters, and histopathology were studied in acute and sub-acute toxicity. Results: During the acute toxicity test, a single oral dose (2000 mg/kg) jaranol did not cause significant alteration in majority of the hematological indices. However, jaranol decreased the level of serum alanine aminotransferase and aspartate aminotransferase. Those results showed that the oral lethal dose 50 (LD50) of jaranol was higher than 2000 mg/kg BW, regardless of sex. In repeated daily oral doses (50, 100 and 200 mg/kg BW·d-1), no mortality was recorded in the various experimental groups. The jaranol reduced body weight gain (200 mg/kg BW·d-1), the relative spleen weight (all doses) and serum alanine aminotransferase activity (200 mg/kg BW·d-1). On the other hand, jaranol significantly elevated red blood cell count (100 and 200 mg/kg BW·d-1) and serum creatinine levels (200 mg/kg BW·d-1). Histological study revealed that spleen bleeding was identified in 200 mg/kg jaranol-treated mice. Conclusion: Jaranol was relatively safe in Kunming Mice when repetitively administered orally in small doses for a prolonged period of time. We recommend more chronic toxicity studies and clinical trials on jaranol to ensure that its use is free of potential toxicity to humans.
| S-EPMC9280858 | biostudies-literature
Project description:Introduction:Solid lipid nanoparticles (SLNs) are considered a promising system in enhancing the oral bioavailability of poorly water-soluble drugs; owing to their intrinsic ability to increase the solubility together with protecting the incorporated drugs from extensive metabolism. Objective:Exploiting such properties, SLNs loaded with gliclazide (GLZ) were developed in an attempt to improve the oral bioavailability and the anti-diabetic action of GLZ, together with prolonging its duration of action for better glycemic control. Methods:SLNs were prepared by ultra-sonication technique using glyceryl behenate (Compritol®888 ATO) as a lipid matrix and poloxamer 188 (PLX) as a stabilizer. A 2*3 asymmetrical factorial design was adopted to study the effect of different stabilizer concentrations at different sonication times on the shape, and size of the particles, PDI and drug loading. The selected optimum formulation was then freeze dried using trehalose di-hydrate as a cryo-protectant in different ratios with respect to glyceryl behenate concentration. After freeze drying, the formulation was tested for in-vitro drug release, pharmacokinetics, and pharmacodynamics. Safety of the selected formula was established after carrying out a subacute toxicity study. Results:The factorial design experiment resulted in an optimum formulation coded 10F2 (150 mg PLX/10 min sonication). Scanning electron micrographs showed spherical particles with smooth surface, whereas a ratio of 2:1 cryo-protectant:lipid was found to be optimum with particle size of 245.9 ± 26.2 nm, polydispersity index of 0.482 ± 0.026, and biphasic in-vitro release with an initial burst effect, followed by a prolonged release phase. On the other hand, the selected SLNs exhibited prolonged drug release when compared with the GLZ commercial immediate release (IR) tablets (Diamicron®). Pharmacokinetics study showed about 5-fold increase in GLZ oral bioavailability loaded in SLNs when compared with raw GLZ powder. Pharmacodynamics study on a diabetic rat model confirmed the better anti-diabetic action of GLZ loaded SLNs when compared to raw GLZ powder. Subacute toxicity study indicated the safety of SLNs upon repetitive oral administration.
| S-EPMC7038779 | biostudies-literature
Project description:Background: Poisoning by different kinds of toxic mushrooms is unfortunately becoming an increasingly important medical problem, evident from the growing number of reports worldwide since the 1950s. Mycetism being a health concern, deserves scientific attention. In this perspective, the present study aims to assess the potential effects of ingesting the selected wild mushrooms from regions of the Western Ghats, India. Methods: The preliminary cytotoxicity of the selected mushrooms was studied in vitro on the intestinal NCM460 and the Chang's liver cell lines on the basis of cell viability. Further, the hepatotoxicity was assessed by measuring biologically relevant endpoints such as membrane integrity, mitochondrial stress and oxidative status. A 28 day sub-acute toxicity study was carried out by orally administering the mushroom extracts to mice at 250 and 500 mg/kg body weight. The hematological and serum analysis as well as histological examinations were carried out to evaluate their in vivo toxicity. GC-MS analysis of the mushrooms facilitated the identification of their volatile chemical profile. Result: The in vitro intestinal cytotoxicity exhibited by these wild mushrooms in comparison to the edible mushroom indicated their potential gastrointestinal toxicity. The pathological findings in small intestine on exposure to Chlorophyllum molybdites and Agaricus endoxanthus also validates the speculations about their intestinal toxicity. The toxic insult to the hepatocytes due to Amanita angustilamellata, Entoloma crassum, and Clarkeinda trachodes was predictive of the observed in vivo hepatotoxicity which was also accompanied by renal toxicity at the higher dose of 500 mg/kg bwt. Conclusion: The potential toxicity exhibited by these representative mushrooms from the wild warrants caution about their consumption. The present work could also have broader implications for global mycetism.
| S-EPMC5816808 | biostudies-literature
Project description:The median lethal dose for rodent oral acute toxicity (LD50) is a standard piece of information required to categorize chemicals in terms of the potential hazard posed to human health after acute exposure. The exclusive use of in vivo testing is limited by the time and costs required for performing experiments and by the need to sacrifice a number of animals. (Quantitative) structure-activity relationships [(Q)SAR] proved a valid alternative to reduce and assist in vivo assays for assessing acute toxicological hazard. In the framework of a new international collaborative project, the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods and the U.S. Environmental Protection Agency's National Center for Computational Toxicology compiled a large database of rat acute oral LD50 data, with the aim of supporting the development of new computational models for predicting five regulatory relevant acute toxicity endpoints. In this article, a series of regression and classification computational models were developed by employing different statistical and knowledge-based methodologies. External validation was performed to demonstrate the real-life predictability of models. Integrated modeling was then applied to improve performance of single models. Statistical results confirmed the relevance of developed models in regulatory frameworks, and confirmed the effectiveness of integrated modeling. The best integrated strategies reached RMSEs lower than 0.50 and the best classification models reached balanced accuracies over 0.70 for multi-class and over 0.80 for binary endpoints. Computed predictions will be hosted on the EPA's Chemistry Dashboard and made freely available to the scientific community.
| S-EPMC6717335 | biostudies-literature
Project description:Tetrorchidium didymostemon is widely used by traditional medicine practitioners to manage and treat several diseases. Despite its known ethnomedicinal uses, there are no scientific studies on the toxic effects of this plant. This study was performed to evaluate the potential toxicity of methanol extracts Tetrorchidium didymostemon leaves through sub-acute oral administration in rats. Twenty four (24) male albino rats (Wistar strain) of average weight 150 ± 20 g were randomly divided into 4 groups of 6 rats each. Group 1 was the control while groups 2, 3 and 4 were administered 100, 300 and 600 mg/kg body weight of the plant extracts respectively for 14 consecutively days. The extract did not induce any treatment related changes in body weight, organ/body weight ratio, biochemical parameters (aspartate transaminase, alanine transaminase, total protein, albumin, creatinine and urea), oxidative stress indices (malondialdehyde, superoxide dismutase and reduced glutathione) and histopathology (liver and kidney) of the treated groups when compared to the control. However, at 600 mg/kg body weight dose, the extract caused a significant (p < 0.05) decrease in hemoglobin level, packed cell volume and the expression of albumin gene of rats. Similarly, at 300 and 600 mg/kg body weight, the extract also caused a non-significant (p > 0.05) decrease in red blood cell count. Furthermore, the extract at 100 and 300 mg/kg body weight induced a significant (p < 0.05) increase in the expression of tumor necrosis factor - alpha and kidney injury molecule - 1 (KIM-1) genes. Catalase gene expression especially in the kidney was up-regulated in the groups administered the extract. Our study suggests that oral administration of T. didymostemon leaves extract is relatively safe. However, there is need for caution due to the observed changes in hematological profile, up-regulation of KIM-1 genes as well as down regulation of albumin gene.
| S-EPMC7327260 | biostudies-literature