Comparative evaluation of acute toxicity of ivermectin by two methods after single subcutaneous administration in rats

Ivermectin was evaluated for its acute toxicity after single subcutaneous (s/c) administration by 'Acute Toxic Class' method as per OECD 423 and by conventional acute toxicity test using probit analysis in rats. 'Acute toxic class' method yielded LD(50) in category 2 i.e. between 5 and 50mg/kg which was comparable with conventional method where it was found to be 51.5mg/kg. Post mortem lesions were observed in the form of congestion of liver, which showed centrilobar necrosis and hemorrhages on histopathological analysis in both the methods. This study suggests, 'Acute Toxic Class' method may be used instead of conventional method to study acute toxicity of injectable preparations. Similarly the LD(50) of around 50mg/kg indicated a wide margin of safety (250x) considering therapeutic dose of ivermectin as 200microg/kg.     

Decreased aortic contractile reaction to 5-hydroxytryptamine in rats with long-term hypertension induced by lead (Pb) exposure

Male Wistar rats were exposed to 100 ppm Pb²⁺ in drinking water for 10 months. Tail blood pressure, serum 5-hydroxytryptamine (5-HT), the expression of 5-HT_2B receptor in the aorta, the aortic response to 5-HT, and the pathologic changes of aorta were examined. The systolic blood pressure of Pb²⁺ exposed group was significantly increased after 2 months of Pb²⁺ exposure. After 10 months of Pb²⁺ exposure, aortic contractile response to 5-HT was significantly decreased. There was no significant difference in the levels of serum 5-HT and the expression of 5-HT_2B receptor between these two groups. The aortic media and the media-lumen ratio of Pb²⁺ exposed group were significantly increased. These data suggest that long-term Pb²⁺ exposure can increase blood pressure, and can alter the function and structure of aortic of rats. The decreased aortic response to 5-HT has little relation to the expression of 5-HT_2B receptor and the serum level of 5-HT, maybe is a result of the aortic structural alteration.     

Acute and chronic toxicity of nano-scale TiO2 particles to freshwater fish,cladocerans, and green algae,and effects of organic and inorganic substrate on TiO2 toxicity

This research evaluated the toxicity of TiO₂ nanoparticles to freshwater aquatic organisms and the effects of organic and inorganic material on TiO₂ toxicity. The fathead minnow was much less acutely sensitive to TiO₂ (LC50 500 mg/l and higher) than Ceriodaphnia dubia and Daphnia pulex (mean LC50 values 7.6 and 9.2 mg/l, respectively). Total organic carbon levels of 1.5 mg/l decreased TiO₂ acute toxicity to C. dubia (LC50 > 100 mg/l), but kaolinite clay decreased TiO₂ toxicity to a lesser extent. In chronic toxicity tests, the green algae Pseudokirchneriella subcapitata was more sensitive to TiO₂ (IC25 1–2 mg/l) than C. dubia (IC25 9.4–26.4 mg/l) and the fathead minnow (IC25 values over 340 mg/l). Study results indicate that the specific organisms exposed and the effects of water quality parameters on TiO₂ toxicity should be considered in hazard evaluations of this nanoparticle.     

The protective effect of rutin against renal toxicity induced by lead acetate

Flavonoids are known to have powerful antioxidant activity that could play a protective role in oxidative stress-mediated diseases. Rutin (RT) is a flavonol glycoside composed of the flavonol quercetin and disaccharide rutinose. The protective effect of RT against nephrotoxicity induced by lead acetate was evaluated. Male albino rats of Wistar strain were used in this study. Animals were given lead acetate after a week of pretreatment with RT (50?mg/animal/day). Lead acetate exposure resulted in an increase in the uric acid, creatinine (CRN) and blood urea nitrogen (BUN) levels and a decrease in glutathione, superoxide dismutase, catalase and glutathione peroxidase (GPx) activities. Lead acetate treatment decreased GSH levels by 2-fold and the activities of GSH metabolizing enzymes decreased to a range of 2–2.5-fold in renal tissue (p?<?0.05). These changes were reversed significantly in animals receiving pretreatment of RT. Treatment of rats with RT prior to the treatment with lead resulted in the recovery of reduced levels of GSH, GSH-metabolizing enzymes to almost 85–90%. RT has a beneficial impact on lead-induced toxicity due to its scavenging and antioxidant effect in rats.     

“红丹膏”致婴幼儿铅中毒原因分析

[目的]分析“红丹膏”引起婴幼儿铅中毒的原因.[方法]分析131例使用“红丹膏”致铅中毒的婴幼儿的中毒程度及年龄分布、患儿父母的受教育程度、患儿所来自的地区,并与 131例体检提示血铅正常的儿童作比较.[结果]使用“红丹膏”致铅中毒的131例患儿中,Ⅱ级铅中毒112例(85.5％),Ⅲ级铅中毒16例(12.2％),Ⅳ级铅中毒3例(2.3％); 127例(96.9％)3岁以下,4例(3.1％)3岁以上;112例(85.5％)患儿父母受教育程度为大专以下;103例(78.6％)患儿来自欠发达地区.[结论]“红丹膏”引起铅中毒主要集中在3岁以下的婴幼儿,多为轻度中毒,与婴幼儿湿疹发生的高峰时间有关,使用“红丹膏”患儿与来源地区的经济状况及其父母的受教育程度有关.     

Significance of the LD50-test for the toxicological evaluation of chemical substances

The LD₅₀-test was developed in 1927 for the biological standardization of dangerous drugs. Then it was incorporated into the routine toxicological protocol of other classes of chemical compounds and is now part of practically all governmental guidelines which regulate toxicological testing of chemicals.For scientific, economic, and ethical reasons it is necessary to periodically reassess all toxicological test procedures, including the LD₅₀-test. Tests which are not optimal or that have become obsolete because of new scientific knowledge, must be changed or eliminated.The review of the LD₅₀-test shows that the precision of the procedure is dependent on the number of animals used. But even with large numbers of animals there are considerable variations of the test results, because the numerical value of the LD₅₀ is influenced by many factors, such as animal species and strain, age and sex, diet, food deprivation prior to dosing, temperature, caging, season, experimental procedures, etc. Thus, the LD₅₀ value cannot be regarded as a biological constant.Through standardization of the test animals and the experimental conditions the variability of the LD₅₀ determinations can be reduced but never fully eliminated.There are several tests with which an approximate LD₅₀ can be determined. These methods use fewer animals than the classical LD₅₀-test, but their precision and reproducibility are sufficient for most purposes of acute toxicity testing.Through incorporation of physiological, hematological, biochemical, pathological, and histopathological investigations in the simplified test procedures with small numbers of animals, it is possible to markedly increase the informational content of the results with regard to the toxicological spectrum and the target organs of toxicity. Such studies have already replaced the LD₅₀-test in large animals, such as dogs and monkeys. It is also desirable to replace the LD₅₀ in rodents with such a procedure.With pharmacologically inert compounds that have no acute effects with single administration the classical LD₅₀-test does not provide relevant toxicological results.For the prediction of the human lethal dose and for the prediction of the symptomatology of poisoning after acute overdosing in man the LD₅₀-test is of limited usefulness. An acute toxicity test with small numbers of animals combined with comprehensive studies of physiological functions, biochemical and histopathological examinations often provides more important information for emergency physicians and poison control centers.For the selection of doses to be used in subacute and chronic toxicity experiments the LD₅₀-test does not provide consistent and reliable results. A simple pilot experiment with few animals but repeated dosing gives more useful information.For the evaluation of special risks for the human newborn and infant the LD₅₀-test is poorly suited.For the appraisal of pharmacokinetic behavior and bioavailability the LD₅₀-test gives only semi-quantitative, often ambiguous information.In all cases where the acute toxicity testing is mainly concerned with the evaluation of toxicological potential of the test substances, the symptomatology following acute overdosing, and the knowledge of target organs of toxicity, the classical LD₅₀-test should be replaced by a more comprehensive short term test that can be done with small numbers of animals. The classical LD₅₀-test should only be permitted in those rare instances where a high precision of the LD₅₀ determination is indispensable.     

A new approach to minimizing the number of animals used in acute toxicity testing and optimizing the information of test results

170 acute toxicity determinations, carried out in rats, mice, and guinea pigs after oral and parenteral administration during the past 5 years, using 5 /5 animals per dose, were evaluated with respect to the possibility of a reduction of animals necessary for obtaining LD₅₀ values with limits of confidence. Calculations were performed on existing data; no additional animal experiments were initiated for the purpose of this paper.For the majority of substances 3 /3 animals per dose would have sufficed for the determination of a LD₅₀ value with limits of confidence. Even when using 2 /2 animals per dose, in most cases sufficently acceptable LD₅₀ values can be determined, if the period of observation — conventionally 4 weeks — would be doubled. Using this procedure, 75% of the animals could be saved. The reduced number of animals and the labor saved thereby would allow for a more individualized observation of single animals thus optimizing the evaluation of acute toxicity testing.     

Acute oral toxicity: Variability,reliability, relevance and interspecies comparison of rodent LD50 data from literature surveyed for the ACuteTox project

The ACuteTox project has aimed to optimise and prevalidate an in vitro testing strategy for predicting human acute toxicity. Ninety-seven reference substances were selected and an in vivo acute toxicity database was compiled. Comprehensive statistical analyses of the in vivo LD₅₀ data to evaluate variability and reliability, interspecies correlation, predictive capacities with regard to EU and GHS toxicity categories, and deduction of performance criteria for in vitro methods is presented. For the majority of substances variability among rodent data followed a log normal distribution where good reproducibility was found. Rat and mouse interspecies comparison of LD₅₀ studies by ordinary regression showed high correlation, with coefficients of determination, ranging between 0.8 and 0.9. Substance specific differences were only significant for warfarin and cycloheximide. No correlation of compound LD₅₀ range with presumed study quality rank (by assigning Klimisch reliability scores) was found. Modelling based on LD₅₀ variability showed that with at least 90% probability ∼54% of the substances would fall into only one GHS category and ∼44% would fall within two adjacent categories. These results could form the basis for deriving a predictive capacity that should be expected from alternative approaches to the conventional in vivo acute oral toxicity test.     

Acute pulmonary inflammation induced by exposure of the airways to staphylococcal enterotoxin type B in rats

Staphylococcus aureus is a gram-positive bacterium that produces several enterotoxins, which are responsible for most part of pathological conditions associated to staphylococcal infections, including lung inflammation. This study aimed to investigate the underlying inflammatory mechanisms involved in leukocyte recruitment in rats exposed to staphylococcal enterotoxin B (SEB). Rats were anesthetized with pentobarbital sodium and intratracheally injected with either SEB or sterile phosphate-buffered saline (PBS, 0.4 ml). Airways exposition to SEB (7.5-250 ng/trachea) caused a dose- and time-dependent neutrophil accumulation in BAL fluid, the maximal effects of which were observed at 4 h post-SEB exposure (250 ng/trachea). Eosinophils were virtually absent in BAL fluid, whereas mononuclear cell counts increased only at 24 h post-SEB. Significant elevations of granulocytes in bone marrow (mature and immature forms) and peripheral blood have also been detected. In BAL fluid, marked elevations in the levels of lipid mediators (LTB(4) and PGE(2)) and cytokines (TNF-alpha, IL-6 and IL-10) were observed after SEB instillation. The SEB-induced neutrophil accumulation in BAL fluid was reduced by pretreatment with dexamethasone (0.5 mg/kg), the COX-2 inhibitor celecoxib (3 mg/kg), the selective iNOS inhibitor compound 1400 W (5 mg/kg) and the lipoxygenase inhibitor AA-861 (200 microg/kg). In separate experiments carried out with rat isolated peripheral neutrophils, SEB failed to induce neutrophil adhesion to serum-coated plates and chemotaxis. In conclusion, rat airways exposition to SEB causes a neutrophil-dependent lung inflammation at 4 h as result of the release of proinflammatory (NO, PGE(2), LTB(4), TNF-alpha, IL-6) and anti-inflammatory mediators (IL-10).     

Further evidence for the subsensitivity of striatal AMPA receptors, induced by chronic haloperidol administration: an autoradiographic study

The aim of the present study was to investigate the influence of chronic treatment with haloperidol on the striatal N-methyl-D-aspartate (NMDA), -amino-3-hydro-xy-5-methyl-4-isoxasole-propionic acid (AMPA) and dopamine D₂ receptors using a quantitative autoradiography in rats. Haloperidol was given to animals in a dose of ca. 1 mg/kg/day in drinking water for 6 weeks or 3 months and was afterwards withdrawn for 5 days. Haloperidol increased by 20–50% the binding of [³H]spiperone in different regions of the caudate-putamen. Haloperidol decreased by ca. 30% the binding of [³H]AMPA in the ventrolateral region of intermediate part of the caudate-putamen, but did not influence the binding of [³H]MK-801. The present results suggest that, apart from supersensitivity to dopamine, chronic treatment with haloperidol also induces subsensitivity of striatal AMPA receptors.     

杀鼠药中毒所致凝血功能障碍20例临床分析

目的 总结杀鼠药中毒导致的凝血功能障碍的临床诊断及治疗。 方法 对20例抗凝血杀鼠药中毒致凝血功能障碍患者予以维生素K₁治疗,比较患者治疗前后的凝血功能改变:凝血酶原时间(PT)、国际正常化比率( INR ),活化部分凝血活酶时间(APTT)、凝血因子Ⅱ、Ⅶ、Ⅸ、Ⅹ活性。 结果 20例患者全部治愈,治疗前后凝血功能明显改变,PT治疗前后分别为:(103.2±20.3)s,(12.0±0.5)s。 INR治疗前后分别为:4.2±2.4,1.4±0.2。APTT 治疗前后分别为:(93.2±25.4)s,(30.2±3.4)s。凝血因子Ⅱ:活性成分治疗前后分别为:(6.2±2.5)%,(92.3±4.5)%。凝血因子Ⅶ:活性成分治疗前后分别为:(10.8±4.9)%,(86.2±3.4)%。凝血因子Ⅸ:活性成分治疗前后分别为:(22.5±6.8)%,(96.4±7.8)%。凝血因子X:活性成分治疗前后分别为:(14.2±3.2)%,(83.2±3.4)%,差异有统计学意义(P<0.001)。 结论 杀鼠药中毒致凝血功能障碍,容易误诊,维生素K₁是特效解毒药。     

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

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

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

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

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

Taurine mitigates cognitive impairment induced by chronic co-exposure of male Wistar rats to chlorpyrifos and lead acetate

Organophosphate pesticides and heavy metals are ubiquitous environmental pollutants and neurotoxicants. We investigated the effects of taurine (an antioxidant; TA) on oxidative stress and cognition in male Wistar rats co-treated with chlorpyrifos (an organophosphate pesticide; CPF) and lead acetate (heavy metal; LA). The Wistar rats were divided into 5 groups of 10 rats each. The first two groups were administered with distilled water and soya oil respectively. The remaining three groups were administered with taurine (TA), 50 mg/kg body weight, CPF + LA group [CPF (4.25 mg/kg, 1/20 LD50] and LA (233.25 mg/kg, 1/20 LD50) and TA + CPF + LA group [TA (50 mg/kg), CPF (4.25 mg/kg) and LA (233.25 mg/kg)]. The xenobiotics were administered once daily by oral gavage for 16 weeks. The results showed reductions in the activities of brain antioxidant enzymes and acetylcholinesterase, increased lipoperoxidation and histopathological alterations of the cerebral cortex in the CPF + LA group. However, TA mitigated perturbations in the activities of the antioxidant enzymes and acetylcholinesterase, counteracted oxidative stress and brain lipoperoxidation and attenuated neuronal degeneration induced by joint CPF and LA-induced neurotoxicity. The results suggested that TA is neuroprotective following chronic co-exposure of rats to CPF and LA.     

The effect of oral administration of Allium sativum extracts on lead nitrate induced toxicity in male mice

Lead is a common environmental occupational toxic metal, known to have indirect oxidative effects. Considering the antioxidant properties of garlic, this study was undertaken to evaluate the therapeutic efficacy of garlic extracts in terms of normalization of altered hematological, biochemical and immunological parameters, and depletion of inorganic lead burden in blood, kidney and brain tissues. Chronic lead nitrate ingestion showed a significant decline in total erythrocyte count, total leukocyte count, hemoglobin concentration, lymphocyte and monocyte content, while neutrophil content increased in lead nitrate treated group. Pb(NO₃)₂ exposure elicited a significant escalation in thiobarbituric acid reactive substances level and depletion in reduced glutathione content and antioxidant enzymes namely, superoxide dismutase and catalase in kidney and brain. Activities of aspartate transaminase, alanine transaminase, acid phosphatase and alkaline phosphatase augmented significantly in kidney and brain of lead exposed mice. Lead nitrate treatment decreased protein content while cholesterol and lead burden increased significantly. A decrease in viability of macrophage, phagocytic index, immunoglobulin level and plaque count were the salient features observed in lead exposed animals. However, oral administration of garlic extracts to Pb(NO₃)₂ treated groups attenuated the deranged parameters to some extent. This indicates that garlic can be a protective regimen for lead toxicity.     

Ascorbic acid ameliorates oxidative damage induced by maternal low-level lead exposure in the hippocampus of rat pups during gestation and lactation

This study was to investigate the effects of ascorbic acid on the hippocampus of suckling rats in the presence of lead (Pb)-induced oxidative stress. Pregnant Sprague-Dawley rats received treatment with drinking water, divided into three groups, as follows: (1) distilled water; (2) 0.2% Pb; (3) 0.2% Pb+ascorbic acid (100mg/kg/day). Rat pups were euthanized at the age of 21days and their brain tissue was examined using light microscopy. Protein levels of Cu/Zn superoxide dismutase (Cu/Zn SOD), manganese superoxide dismutase (Mn SOD), and catalase (CAT) in the hippocampus were determined by Western blotting. We found a significant decrease in levels of Cu/Zn SOD and Mn SOD among Pb-exposed pups. Ascorbic acid supplementation appeared to negate the decrease in protein levels for Cu/Zn SOD and Mn SOD. In the case of CAT, there was no effect from Pb administration alone and Pb plus ascorbic acid appeared to increase the levels. In histopathology, ascorbic acid decreased the number of damaged cells in cornu ammonis areas CA1, CA3, and the dentate gyrus (DG) in hippocampus. Our results showed that administration of ascorbic acid during pregnancy and lactation could ameliorate some of the oxidative damage induced by Pb exposure in the developing rat hippocampus.     

Involvement of endothelial thromboxane A2 in the vasoconstrictor response induced by 15-E2t-isoprostane in isolated human umbilical vein

The present study was undertaken to evaluate the contractile response of several E- and F-ring isoprostanes (IsoP) in human umbilical vein (HUV) and to investigate the role of the endothelium on the effect of 15-E_2t-IsoP, the most potent vasoconstrictor isoprostane, in human vessels. HUV rings with or without endothelium were suspended in an organ bath for recording the isometric tension in response to different agonists. The inhibitors to be evaluated were applied 30 min before the addition of the agonist. All of the compounds tested produced concentration-dependent contractions when tested on HUV rings with endothelium. Although these compounds were equieffective, significant differences were observed in their potency, with U46619 being the most potent followed by 15-E_2t-IsoP > 15-E_1t-IsoP = 15-F_2t-IsoP > 15-F_1t-IsoP = 9-epi-15-F_2t-IsoP in descending rank order of potency. 15-E_2t-IsoP was the most potent of the isoprostanes evaluated and, therefore, the one employed in the present study. When intact endothelium HUV rings were used, 15-E_2t-IsoP-induced contraction was unaffected by the endothelin-converting enzyme inhibitor, phosphoramidon (10 μM), suggesting that short-term endothelin-1 release is not involved in this response. However, the non-selective cyclooxygenase (COX) inhibitor, indomethacin (10 and 30 μM), and the COX-2 selective inhibitor, NS-398 (3, 10 and 30 μM) produced inhibitory effects on 15-E_2t-IsoP-induced contraction of HUV rings with endothelium. These results indicate that COX-derived contractile prostanoids are involved in this effect. Furthermore, the apparent pK _b values estimated for indomethacin (5.5) and NS-398 (5.4) suggest that the prostanoids involved are derived from the COX-2 isoenzyme pathway. On HUV rings with endothelium, the phospholipase A₂ inhibitor, oleyloxyethyl phosphorylcholine (30 and 100 μM), induced an inhibitory effect on 15-E_2t-IsoP-induced contraction, suggesting that the phospholipase A₂ pathway is also involved in this effect. In addition, the thromboxane A₂ synthase inhibitor furegrelate (10 and 30 μM) also inhibited 15-E_2t-IsoP-induced contraction of HUV rings with endothelium, indicating that thromboxane A₂ is one of the contractile prostanoids involved in this response. Endothelium denudation clearly diminished the vasoconstrictor potency of 15-E_2t-IsoP, demonstrating that the endothelium releases a vasoconstrictor factor in response to 15-E_2t-IsoP. The absence of an inhibitory effect at the highest concentration of furegrelate (30 μM) on 15-E_2t-IsoP-induced contraction of HUV rings without endothelium suggested that endothelium is the source of thromboxane A₂. We conclude that prostanoids derived from the COX-2 isoenzyme pathway participate in 15-E_2t-IsoP-induced vasoconstriction of isolated HUV rings. Our results also indicate that endothelial thromboxane A₂ is one of the prostanoids involved in this effect.     

In praise of H2O2, the versatile ROS,and its vanadium complexes

Hydrogen peroxide (H₂O₂) is generated in mitochondria in aerobic cells as a minor product of electron transport, is inhibited selectively by phenolic acids (in animals) or salicylhydroxamate (in plants) and is regulated by hormones and environmental conditions. Failure to detect this activity is due to presence of H₂O₂-consuming reactions or inhibitors present in the reaction mixture. H₂O₂ has a role in metabolic regulation and signal transduction reactions. A number of enzymes and cellular activities are modified, mostly by oxidizing the protein-thiol groups, on adding H₂O₂ in mM concentrations. On complexing with vanadate, also occurring in traces, H₂O₂ forms diperoxovanadate (DPV), stable at physiological pH and resistant to degradation by catalase. DPV was found to substitute for H₂O₂ at concentrations orders of magnitude lower, and in presence of catalase, as a substrate for user reaction, horseradish peroxidase (HRP), and in inactivating glyceraldehyde-3-phosphate dehydrogenase. superoxide dismutase (SOD) -sensitive oxidation of NADH was found to operate as peroxovanadate cycle using traces of DPV and decameric vanadate (V₁₀) and reduces O₂ to peroxide (DPV in presence of free vanadate). This offers a model for respiratory burst. Diperoxovanadate reproduces several actions of H₂O₂ at low concentrations: enhances protein tyrosine phosphorylation, activates phospholipase D, produces smooth muscle contraction, and accelerates stress induced premature senescence (SIPS) and rounding in fibroblasts. Peroxovanadates can be useful tools in the studies on H₂O₂ in cellular activities and regulation.     

Effect of strontium chloride on bone resorption induced by prostaglandin E2 in cultured bone

We examined whether the bone resorption induced by PGE₂ was inhibited by SrCl₂ using⁴⁵Ca-labelled calvaria of CD-strain mice in tissue culture. It was found that Sr salts inhibited physiological bone resorption in a dose-dependent manner (0.1–5.0 mM) and did not act via PGE₂. Accordingly, it was suggested that Sr salts did not inhibit bone resorption induced by exogenous PGE₂.Abbreviations PGE₂ Prostaglandin E₂ - PTH Parathyroid hormone - CT Calcitonin - Vit. D₃ Vitamin D₃ - HSDM₁ Harvard School of Dental Medicine 1     

Safety assessment of methanol extract of red dragon fruit (Hylocereus polyrhizus): Acute and subchronic toxicity studies

Recently, the fruits of Hylocereus polyrhizus, known as red dragon fruit, have received much attention from growers worldwide. However, there is little toxicological information regarding the safety of repeated exposure to these fruits. The present study evaluated the potential toxicity of a methanol extract of H. polyrhizus fruit after acute and subchronic administration in rats. In the acute toxicity study, single doses of fruit extract (1250, 2500 and 5000 mg/kg) were administered to rats by oral gavage, and the rats were then monitored for 14 days. In the subchronic toxicity study, the fruit extract was administered orally to rats at doses of 1250, 2500 and 5000 mg/kg/day for 28 days. There was no mortality or signs of acute or subchronic toxicity. There was no significant difference in body weight, relative organ weight or hematological parameters in the subchronic toxicity study. Biochemical analysis showed some significant changes, including creatinine, globulin, total protein and urea levels. No abnormality of internal organs was observed between treatment and control groups. The lethal oral dose of the fruit extract is more than 5000 mg/kg and the no-observed-adverse-effect level (NOAEL) of the extract for both male and female rats is considered to be 5000 mg/kg per day for 28 days.