Subchronic Oral Toxicity of Pyridostigmine Bromide in Rats

This study evaluated the oral toxicity of pyridostigmine bromide in Sprague-Dawley rats when administered for 13 weeks by daily gavage. Groups of 10 rats/sex received doses of 0, 5, 15, 30, or 60 mg/kg/day. Toxicity was limited to exaggerated cholinergic stimulation at doses of 15 mg/kg/day or greater. Significant findings included tremors and inhibition of RBC acetylcholinesterase. Thus, 5 mg/kg/day of pyridostigmine bromide appears to be the no observed toxic effect level under the conditions of the present investigation.

Acute oral toxicity test and assessment of rhynchophylline in mice

As the main alkaloid constituent of Uncaria species,rhynchophylline has drawn extensive attention in recent years for its antihypertensive and neuroprotective activities.However,toxicity study of the rhynchophylline is still lacking.In the present study,oral acute toxicity of rhynchophylline was conducted in Kunming mice.The mice were orally treated with 520.00,442.00,375.70,319.34 and 271.44 mg/kg of rhynchophylline for 14 d.The general behavior,body weight changes,toxic reaction,and death were recorded,and histopathological analyses were performed.The acute toxicity was evaluated by the assessment of the median lethal dose(LD50).The acute toxicity study showed that no significant difference was found in the body weight of the mice in the control group and those in the drug group.However,the mice treated with rhynchophylline showed obvious abnormal symptoms and mortality.The median lethal dose(LD50)of orally administered rhynchophylline was 308.08 mg/kg.The histopathological results showed that the mice in the high-dose rhynchophylline group displayed toxic effects in the brain,liver,lung,and kidney.The results of the current study indicated that rhynchophylline could not be taken at a high dose.Collectively,our current findings provided a strong basis for further clinical investigation.

Acute Toxicity of Aluminium Phosphide Following Oral Administration in Rats

Aluminium phosphide (AlP) is used as a fumigant and also sometimes misused for suicidal attempts in India, due to its easy availability. The effect of phosphine, the gas that is liberated when AlP comes in contact with moisture, is well documented in the literature. However, the effect of AlP in its native form on animal models is not well cited. In this study we examined the acute toxic effect of AlP in rats. Oral LD50 of AlP for male and female rats were found to be 14. 13 and 11. 89mg/kg, respectively. Oral administration of an AlP dose of 0. 80 LD50 resulted in significant increases in the level of plasma glutamic oxaloacetic transaminase,alkaline phosphatase, glucose and urea in rats of both sexes. Hemoglobin level and packed cell volume also increased significantly 6h after administration. Body weight was reduced but the organ to body weight ratio of lung, liver, spleen, kidney and testes remained unchanged.Histopathological changes induced by AlP during 24-48h induced hemorrhage, congestion and mild to moderate atrophy of various cellular components of visceral organs. The study showed that the acute toxic effect of AlP may be due to hypovolemic shock. Female rats were found to be more susceptible than were males.

Modulation of the in vitro Oxidative Stress and Erythrocyte Cell Membrane Integrity Using Aqueous, Hydroethanolic and Ethanolic Stem-Barks Extracts of Greenwayodendron suaveolens (Engl. & Diels) Verdc

Pneumonia, a respiratory infection induces acute or chronic inflammation, characterized by increased activity of lymphocytes and neutrophils, thus generating oxygen-free radicals that decrease the endogenous antioxidants defence system. The aim of this experimental study focused on the capacity of nontoxic aqueous, hydroethanolic and ethanolic extracts of Greenwayodendron suaveolens (Engl. & Diels) Verdc. subsp. suaveolens to regulate free reactive species and protein inflammation generated by infectious disease. The phytochemical screenings of G. suaveolens extracts were carried out according to precipitation and colorimetric methods. The total antioxidant and flavonoid contents were determined by the Folin-Ciocalteu and Aluminium Chloride ethanolic methods. The efficiency of G. suaveolens extracts on free radicals was evaluated using DPPH•, ABTS+•, and FRAP methods. The anti-inflammatory properties of extracts were evaluated according to in vitro protein (BSA) denaturation, Proteinase Inhibitory Action, and Red Blood Cell Membrane stabilization assays. The G. suaveolens aqueous, hydroethanolic and ethanolic extracts were used for the acute toxicity assessment according to the OECD protocol. The obtained results showed the presence of flavonoids, phenols, polyphenols, tannins, anthocyanins, alkaloids, terpenoids, and sterols as secondary metabolites families in G. suaveolens extracts. The highest contents of total antioxidants and flavonoids were highlighted in the hydroethanolic extract. However, it’s the G. suaveolens aqueous extract that showed the best free radical DPPH• and ABTS+• scavenging activities (SC50) of 11.06 μg/mL and 15.16 μg/mL respectively. The highest ferric-reducing activity was found in G. suaveolens ethanolic extract with 866.23 μg EGA/mg of dry weight. The hydroethanolic extract has shown a high anti-inflammatory activity through BSA denaturation and erythrocyte membrane haemolysis with inhibitory concentrations 50 (IC50) of 48.63 and 59.22 μg/mL respectively. In contrast, proteinase inhibitory activity revealed a better potential of IC50 (34.19 μg/mL) for the ethanolic extract. In oral acute toxicity, all treated groups revealed neither mortality nor any significant alteration in behaviour and locomotion. The lethal dose 50 (LD50) of G. suaveolens extracts was >5000 mg/kg. These results suggest that G. suaveolens stem-barks extracts may serve as therapeutic sources to prevent inflammation induced by oxidative stress, an important feature of infectious diseases.

Synthesis, hypoglycemic activity and toxicity study of vanadium oxide complex with genistein

OBJECTIVE Vanadium is a necessary trace element in the human body and has a certain role in the treatment and prevention of diabetes.Organic vanadium is more easily absorbed and less toxic than inorganic vanadium.Thus,in this study,vanadium complex was synthesized from genistein which had good hypoglycemic activity and inor⁃ganic vanadium element,and its hypoglycemic activity and acute oral toxicity were studied.METHODS The vanadium genistein complex was synthesized by chelating vanadium with genistein in methanol and its structure was determined by LC-MS,atomic absorption spectroscopy,UV-visible spectroscopy,elemental and thermodynamic analysis.The antidiabetic activity of the complex was assessed in db/db mice and C57 mice by daily oral gavage for 4 weeks.These db/db mice were divided into test groups〔high(30 mg·kg^-1),medium(20 mg·kg^-1)and low(10 mg·kg^-1)dose group〕,model group,genistein group,inorganic vanadium group,each group of 8;8 C57 mice was for normal control group.The acute toxicity test was carried out on KM mice with this complex by a maximum limit dose method.Randomly 20 healthy KM mice were divided into negative control group and test group,each group of 10,male and female half.RESULTS The molecular structure of this complex was inferred as a complex(VL2)formed by two ligands and one vanadium element.It was found that its hypoglycemic activity was better than that of genistein and inorganic vanadium.The hypoglycemic activity of the high dose group was better than that of the medium dose group and low dose group.The complex can signifi⁃cantly improve the body mass of db/db mice,fasting blood glucose,random blood glucose,liver/body,kidney/body,and the performance of oral glucose tolerance test and insulin tolerance test in db/db mice.The morphology of liver,kidney,pancreas and skeletal muscle also had obvious improvement and repair.Effect on serum index of db/db mice showed that,total cholesterol,triglyceride,low-density lipoprotein cholesterol had no significant improvement compared with the model group,but high-density lipoprotein cholesterol of complex group had significant improvement compared with the model group.In addition,this complex did not produce any hazardous symptoms or deaths in acute oral toxicity test.CONCLUSION complex has good hypoglycemic activity in vivo,and did not have the potential toxicity.This would provide an important reference for the development of functional hypoglycemic foods.

Phytochemical Profile, Antioxidant, and Anti-Inflammatory Activities, Safety of Use and Spasmolytic Effects of Aqueous Decoction Extract of Diospyros mespiliformis Leaves Hochst. ex A. DC. (Ebenaceae) on the Isolated Duodenum of Rat

Diospyros mespiliformis Hochst. ex A. DC. (Ebenaceae) is a multi-use plant, including for therapeutic purposes. It is used in alternative medicine in Burkina Faso to treat conjunctivitis, menorrhagia, dysentery, and diarrhea. The aim of our study was to evaluate the chemical profile, antioxidant and anti-inflammatory activities, safety of use and spasmolytic effects of the aqueous decoction of Diospyros mespiliformis leaves. Phytochemical screening by HPTLC and assay of compounds of interest were carried out. Four methods were used to assess antioxidant activity. Inhibitory activity against 15-lipoxygenase and phospholipase A2 was assessed. Acute oral toxicity of the extract was tested on female mice (NMRI). Following these tests, the extract contained bioactive compounds of interest such as flavonoids, tannins, sterols, triterpenes, and saponosides. The total phenolic and flavonoid contents of the aqueous decoctate were 70.59 ± 3.20 mg EAT/g and 31.57 ± 0.78 mg EQ/g respectively. The extract was less active than Trolox with inhibitory concentrations of 50% (IC50) for the ABTS, DPPH, FRAP, and LPO tests of 7.53 ± 0.08 μg/mL, 29.47 ± 0.06 μg/mL, 1128.83 ± 4.82 mol EAA/g, and 32.30 ± 1.60 μg/mL respectively. The extract has an anti-inflammatory effect with inhibition of phospholipase A2 compared to betamethasone. In addition, the aqueous extract produced an antispasmodic effect with Emax of 70% and 80% respectively during contractions induced by BaCl2 and ACh. Finally, this study provided basic scientific data and could justify the use of D. mespiliformis leaves in the treatment of diarrhea.

Safety Evaluation of the Dichloromethane Extract of Hysterionica pinifolia: A Potential Raw Material for the Development of Biopesticides

At the moment, there is a growing concern about the negative effects on human health and the environment due to the widespread and indiscriminate use of conventional insecticides. Since plants have been used throughout history to control microorganisms and insects, the safety is an aspect that must also be evaluated to guarantee that its use does not affect human health and the environment. The aim of the present study was to evaluate the safety of the dichloromethane extract of Hysterionica pinifolia, species with insecticidal activity, to be employed as a raw material for the development of biopesticides. The acute and subacute toxicity and the dermal and ocular irritation were evaluated. In these studies, the dichloromethane extract of H. pinifolia showed no ocular and a slight dermal irritation. Oral acute toxicity was greater than 2000 mg/Kg and less than 5000 mg/Kg (slightly hazardous) and no signs of toxicity were observed at repeated doses of 100 mg/kg body weight. These promising results showed that Hysterionica pinifolia could be considered as a potential raw material for the development of an insecticide from natural sources, safe for human health and the environment.

Evaluation of Toxicological Profile of a Polyherbal Formulation

In current study toxicological profile of a commonly used herbal formulation was evaluated that is used extensively for gynecological disorders like menorrhagia, metrorrhagia, leucorrhea, irregular menstrual cycle, pre-menstrual syndrome and post-menopausal bleeding. It was also claimed to strengthen endometrium and ovaries. Since this herbal formulation was been used by a large number of population hence there was a need to assess acute and sub-chronic toxicity. Acute oral toxicity (LD50) was observed in albino mice using standard protocols whereas sub-chronic, hematological and histopathological studies were assessed on 24 albino rabbits after giving herbal formulation for 60 days in two doses (20 and 60 mg/kg) against control groups. The outcomes of present study showed that the drug is safe up to 5000 mg/kg following acute oral toxicity test and no mortality was observed during sub chronic toxicity studies. Results of sub-chronic toxicity did not show any significant changes in biochemical, hematological and histopathological parameters. However, some indicators such as urea, creatinine, hemoglobin, and RBC count were altered, but these changes do not correlate with the histopathological results and may be associated to intra individual variations. Despite the safety of the drug in few animals, clinical trials and more investigations on a large number of animals are essentially needed to establish safety and efficacy of the herbal formulation.

Safety of the Aqueous Extract of the Leaves of Senna alata (L.) Roxb. (Leguminosae-Caesalpinioideae), a Plant Used in Benin to Treat Infections

Description of the Subject: Senna alata (L.) was a plant in the Benin pharmacopoeia used to treat skin infections. Objectives: The aim of our work was to test its harmlessness in vivo. Method: Wistar rats received by gavage a single dose of 2000 mg/kg of Senna alata leaves aqueous extract for the Acute Oral Toxicity (AOT) test. For the sub-Chronic Oral Toxicity (SCT) test, rats force-fed the extract at a daily dose of 300 mg/Kg of body weight for 28 days. The weight of the rats was taken and the blood samples were collected on Day 0, then respectively day 14 for the AOT and Day 28 for the SCT. The renal balance was carried out by dosage of the creatinine, the liver balance by the transaminases AST and ALT and the blood balance by the hemogram. The liver, kidneys and spleen were removed for histological analysis. The results were analyzed using the Student test, with the significance level set at 5%. Results: The weight of the rats did not change significantly in the acute or subchronic oral toxicity tests suggesting an absence of physical disturbance in the rats. Serum creatinine did not vary significantly, suggesting preservation of renal function. That was the same for ASAT and ALAT transaminases, indicating an absence of hepatic cytolysis. In hematology, the hemoglobin level and the number of blood platelets did not vary significantly, suggesting that the extract did not create anemia and did not influence blood coagulation. Hepatic, renal and splenic parenchyma showed no atypia. Conclusion: The aqueous extract of Senna alata (L.) leaves did not reveal any acute or subchronic toxicity and offered prospects for its use in the treatment of infections.

Acute and 28-day repeated oral toxicological evaluation of Kuruthi Azhal Chooranam-a Siddha preparation on rodents

Objective:To determine the effect of phytochemicals in acute and repeated dose of 28-day oral toxicity of Kuruthi Azhal Chooranam(KAC)in Sprague Dawley rats of both sexes.Methods:Acute oral toxicity was conducted with 2000 mg/kg body weight of KAC orally and the treated animals were observed for signs of toxicity at 30 min,1,2,4 and 24 h and for up to 14 days.In repeated 28-day oral toxicity study,the KAC formulation was administered orally with 600,900 and 1200 mg/kg body weight/day to all the three groups of rats.The animals were observed for clinical signs of toxicity,mortality and morbidity throughout the study.Also body weight,feed consumption,haematological,plasma biochemistry and serum electrolytes,gross pathology,weights of the organ and histology were studied for no-observed-adverse-effect level.High dose of KAC formulation and control reversal groups were also included for delayed toxic effects determination.Results:In the acute toxicity study of KAC formulation,2000 mg/kg body weight dose exhibited no toxic signs and mortality during study.In sub-acute 28-day repeated dose toxicity study,there was no significant difference found between control and KAC treated groups(body weight,haematology,biochemistry and serum electrolytes).No abnormalities was found in gross pathology,organs weight and histological observation after KAC treatment.Conclusions:The current study suggests that LD_(50)of KAC was>2000 mg/kg and no-observed-adverse-effect level was>1200 mg/kg/day in rats.KAC could be used as Siddha drug for various indications.