SciCombinator

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Concept: Acute toxicity

169

The objective of the study is a comparative evaluation of flavone isolated from Mucuna pruriens and coumarin isolated from Ionidium suffruticosum was assessed for the hypolipidemic activity in rats fed with high fat diet. The acute toxicity study was found that flavone (M.pruriens) and coumarin (I.suffruticosum) are safe up to 100mg/kg, so one tenth of this dose (10mg/kg) was consider as a evaluation dose. High fat diet group of rats showed significant (p<0.001) elevation in plasma total and LDL-cholesterol, triglycerides and phospholipids. Administration of flavone (M. pruriens) and coumarin isolated from (I.suffruticosum) at the dose of 10mg/kg b.wt/day along with high fat diet significantly (p<0.001) prevented the rise in the plasma total and LDL-cholesterol, triglycerides and phospholipids than that of other extracts. However, treatment of coumarin isolated from (I.suffruticosum) had showed more cardio protective effect against hyperlipidemia than that of flavone (M.pruriens).

Concepts: Cholesterol, Fatty acid, Statin, Toxicology, Acute accent, Glycerol, Acute toxicity, Mucuna pruriens

168

Copper is an essential element in various metabolisms. The investigation was carried out to evaluate acute gastroprotective effects of the Copper (II) complex against ethanol-induced superficial hemorrhagic mucosal lesions in rats.

Concepts: Chemical element, Toxicology, Acute toxicity, Alchemy, Schiff base, Peter Slabakov, Hugo Schiff

28

The present investigation was carried out to evaluate the safety of hydro-ethanol extract of Bridelia ferruginea Benth (Euphorbiaceae) root bark. For acute toxicity study, a single dose of 2000 and 5000mg/kg of the B. ferruginea root bark extract was given orally to healthy male Wistar rats and Balb/c mice. The animals were observed for mortality and clinical signs for 3h and then daily for 14days. In the sub-chronic toxicity study, the extract was administered orally at doses of 250, 500 and 1000mg/kg/day for 28days to male Wistar rats. Animals were sacrificed to examine their organs, and urine and blood serum were analyzed. In the acute toxicity study, B. ferruginea root bark extract caused neither significant visible signs of toxicity, nor mortality in Wistar rats and Balb/c mice. In sub-chronic toxicity study, administration of the B. ferruginea root bark extract at 250, 500, and 1000mg/kg for 28 consecutive days to Wistar rats did not produce mortality. No significant differences were found in relative organ weights, biochemical studied parameters in treated groups compared to control group. No obvious histological changes were observed in organs of B. ferruginea extract treated animals compared to controls.

Concepts: Coral, Organ, Toxicology, Rat, Rodent, Mouse, Blood plasma, Acute toxicity

28

ETHNOPHARMACOLOGICAL RELEVANCE: The stem-barks of Hintonia latiflora and H. standleyana, locally known as “copalchi”, are used for treating several maladies such as diabetes and gastrointestinal complaints, including gastric ulcers. Although the antidiabetic properties have been demonstrated, the gastroprotective action remains unexplored. AIM OF THE STUDY: The main goals of this study were to establish the potential acute toxicity and the gastroprotective activity of aqueous extracts and compounds from H. latiflora and H. standleyana in order to demonstrate their preclinical efficacy for the treatment of gastric ulcers in Mexican folk medicine. MATERIALS AND METHODS: The aqueous extracts from the stem-barks (HLSB and HSSB) and leaves (HLL and HSL) from H. latiflora and H standleyana were prepared by infusion. Investigation of the acute toxicity was accomplished by the Lorke method. The gastroprotective effect was assessed by means of a conventional ethanol-induced gastric injury model in rats using carbenoxolone as positive control. 5-O-[β-D-apiofuranosyl-(1→6)-β-D-glucopyranosyl]-7-methoxy-3',4'-dihydroxy-4-phenylcoumarin (1) and chlorogenic acid (2) were also assayed. Preliminary mechanism of action of the tested compounds was analyzed using the same pharmacological models but pretreating the animals with N(G)-nitro-L-arginine methyl ester (L-NAME), N-ethylmaleimide (NEM) and indomethacin. RESULTS: Investigation of the acute toxicity revealed that infusions of the leaves and stem-barks of both Hintonia species were not toxic to mice (LD(50)>5000mg/kg in all cases). HLSB, HSSB, HLL and HSL provoked a significant gastroprotective effect [80.5±3.35% (ED(50)=184.7mg/kg), 80.26±3.96%, 75.1±7.26% % (ED(50)=109.1mg/kg), 76.85±3.17% (ED(50)=149.7mg/kg) of gastroprotection respectively]. Compounds 1 and 2, present in all the extracts, were also active [68.85±8.4% (ED(50)=15mg/kg), 74.04±4.4% (ED(50)=26mg/kg) of gastroprotection respectively] and their mode of action involved non-protein sulfhydryl endogenous (NP-SH) compounds, since only pretreatment with NEM inhibited their gastroprotective action. CONCLUSIONS: The present investigation tends to support the ethnomedical use of HLSB, HSSB for treating gastric ulceration. Since HLL and HSL were also active, the leaves could be use alternatively, which in terms of natural resources conservation is an outstanding finding, considering that the plant populations of both Hintonia are scarce and in danger of extinction. Mainly two compounds (1 and 2) are important active principles of the plants.

Concepts: Present, Toxicology, Ester, Helicobacter pylori, Acute accent, Acute toxicity, Traditional medicine, Hintonia latiflora

27

Abstract Context: Muntingia calabura L. (Muntingiaceae) is a native plant species of the American continent and is widely cultivated in warm areas in Asia, including Malaysia. The plant is traditionally used to relieve pain from gastric ulcers. Objective: This study was designed to determine the antiulcer activity of a methanol extract of M. calabura leaves (MEMC) and the possible mechanisms of action involved. Materials and methods: An acute toxicity study was conducted using a single oral dose of 2000 mg/kg MEMC. The antiulcer activity of MEMC was evaluated in absolute ethanol- and indomethacin-induced gastric ulcer rat models. MEMC was administered orally (dose range 25-500 mg/kg) to rats fasted for 24 h. The animals were pretreated with N(G)-nitro-l-arginine methyl esters (l-NAME) or N-ethylmaleimide (NEM) prior to MEMC treatment to assess the possible involvement of endogenous nitric oxide (NO) and nonprotein sulfhydryl (NP-SH) compounds in the gastroprotective effect of MEMC. Results: As the administered dose did not cause toxicity in the rats, the oral median lethal dose (LD50) of MEMC was >2000 mg/kg in rats. MEMC exerted significant (p < 0.001) gastroprotective activity in the ethanol- and indomethacin-induced ulcer models dose-dependently. Histological evaluation supported the observed antiulcer activity of MEMC. l-NAME and NEM pretreatment significantly (p < 0.05) reversed and abolished the gastroprotective effect of MEMC, respectively. Discussion and conclusion: The results obtained indicate that MEMC has significant antiulcer activity that might involve the participation of endogenous NO and NP-SH compounds. These findings provide new pharmacological information regarding the potential use of M. calabura.

Concepts: Stomach, Toxicology, Peptic ulcer, Acute toxicity, Median lethal dose, Muntingia, Certain safety factor, Sodium nitrite

23

Octahedral rhenium cluster complexes may have considerable potential as therapeutic and diagnostic drugs due to their luminescent and X-ray contrast properties, as well as their ability to generate singlet oxygen upon photoirradiation. However, their potential biological effects and toxicity in vitro and in vivo are rather far from being understood. Thus, the aim of our research was to study cytotoxicity, intracellular localization and cellular uptake/elimination kinetics in vitro, biodistribution and acute intravenous toxicity in vivo of a complex Na4[{Re6Te8}(CN)6] as the promising compound for biomedical application. The results have demonstrated that the complex penetrates through cell membranes with the maximum accumulation in cells in 24h of incubation and have low toxic effects in vitro and in vivo. The median lethal dose (LD50) of intravenously administrated Na4[{Re6Te8}(CN)6] is equal to 1082±83mg/kg. These findings will be useful for future development of cluster-based agents for different biomedical applications.

Concepts: Cell membrane, Magnetic resonance imaging, Toxicology, Cytotoxicity, In vitro, Toxicity, Acute toxicity, Median lethal dose

13

Herbicide use is among the most criticized aspects of modern farming, especially as it relates to genetically engineered (GE) crops. Many previous analyses have used flawed metrics to evaluate herbicide intensity and toxicity trends. Here, I show that herbicide use intensity increased over the last 25 years in maize, cotton, rice and wheat. Although GE crops have been previously implicated in increasing herbicide use, herbicide increases were more rapid in non-GE crops. Even as herbicide use increased, chronic toxicity associated with herbicide use decreased in two out of six crops, while acute toxicity decreased in four out of six crops. In the final year for which data were available (2014 or 2015), glyphosate accounted for 26% of maize, 43% of soybean and 45% of cotton herbicide applications. However, due to relatively low chronic toxicity, glyphosate contributed only 0.1, 0.3 and 3.5% of the chronic toxicity hazard in those crops, respectively.

Concepts: Agriculture, Toxicology, Relative, Acute toxicity, Chronic toxicity, Herbicide, Glyphosate, Roundup

11

Inhalation toxicity testing, which provides the basis for hazard labeling and risk management of chemicals with potential exposure to the respiratory tract, has traditionally been conducted using animals. Significant research efforts have been directed at the development of mechanistically based, non-animal testing approaches that hold promise to provide human-relevant data and an enhanced understanding of toxicity mechanisms. A September 2016 workshop, “Alternative Approaches for Acute Inhalation Toxicity Testing to Address Global Regulatory and Non-Regulatory Data Requirements”, explored current testing requirements and ongoing efforts to achieve global regulatory acceptance for non-animal testing approaches. The importance of using integrated approaches that combine existing data with in vitro and/or computational approaches to generate new data was discussed. Approaches were also proposed to develop a strategy for identifying and overcoming obstacles to replacing animal tests. Attendees noted the importance of dosimetry considerations and of understanding mechanisms of acute toxicity, which could be facilitated by the development of adverse outcome pathways. Recommendations were made to (1) develop a database of existing acute inhalation toxicity data; (2) prepare a state-of-the-science review of dosimetry determinants, mechanisms of toxicity, and existing approaches to assess acute inhalation toxicity; (3) identify and optimize in silico models; and (4) develop a decision tree/testing strategy, considering physicochemical properties and dosimetry, and conduct proof-of-concept testing. Working groups have been established to implement these recommendations.

Concepts: Game theory, Risk, Animal testing, In vivo, Toxicology, Respiratory system, In vitro, Acute toxicity

6

There are sporadic cases of fatalities from acutely eating salt. Yet, on social media, there are “challenges to” and examples of children and some adults acutely eating salt, and recently a charity advocated eating small amounts of salt to empathize with Syrian refugees. We performed a systematic review of fatalities from ingesting salt to assess if relatively moderate doses of salt could be fatal. In 27 reports, there were 35 fatalities documented (19 in adults and 16 in children). The lethal dose was estimated to be less than 10 g of sodium (<5 teaspoons of salt) in two children, and less than 25 g sodium in four adults (<4 tablespoons of salt). The frequency of fatal ingestion of salt is not able to be discerned from our review. If investigation of the causes of hypernatremia in hospital records indicates salt overdose is relatively common, consideration could be given to placing warning labels on salt containers and shakers. Such warning labels can have the added advantage of reducing dietary salt consumption.

Concepts: Eating, Ingestion, Dose, Toxicology, Sodium, Potassium, Salt, Acute toxicity

4

Although the recreational use of psychoactive substances is common there is only limited systematic collection of data on acute drug toxicity or hospital presentations, in particular regarding novel psychoactive substances (NPS) that have emerged on the illicit market in the last years.

Concepts: Hospital, Drug, Toxicology, Opioid, Psychoactive drug, Acute toxicity, Recreational drug use, Median lethal dose