Chemical characterization and toxicological assessment of hydroethanolic extract of Mandevilla velame xylopodium

Abstract The present study was aimed to characterize the chemical profile and evaluate the cytotoxicity and sub-chronic toxicity of the hydroethanolic extract of the xylopodium Mandevilla velame (A.St.-Hil.) Pichon, Apocynaceae. Chemical profile was analyzed by high performance liquid chromatography. Cytotoxic potential of hydroethanolic extract of the xylopodium M. velame was evaluated using Chinese hamster ovary cells. The sub-chronic assessment was done on rats with hydroethanolic extract of the xylopodium M. velame (50, 200 and 800 mg/kg) was orally administered daily for 30 consecutive days. High performance liquid chromatography analysis confirmed the presence of gallic acid, ellagic acid, catechin, epigallocatechin gallate, naringin, myricetin, quercetin and naringenin. hydroethanolic extract of the xylopodium M. velame tested concentrations did not alter the viability of Chinese hamster ovary cells. In the sub-chronic test, 50 and 200 mg/kg were safe, but there were significant changes in relation to weight gain and water consumption by animals that received 800 mg/kg of hydroethanolic extract of the xylopodium M. velame. Among the haematological and biochemical parameters evaluated, only the number of neutrophils, lymphocytes, and creatinine concentration were changed at 800 mg/kg. Phytochemical profile of hydroethanolic extract of the xylopodium M. velame revealed the presence of phenolics and flavonoid compounds. The in vitro cytotoxicity assay result demonstrated that hydroethanolic extract of the xylopodium M. velame had no cytotoxic effects in Chinese hamster ovary cells. In the in vivo models, hydroethanolic extract of the xylopodium M. velame was shown to be relatively safe after sub-acute administration in rats which is relation to that the population daily takes a total dose of the plant xylopodium decoction or infusion about 23.29 times lower than the no-observed-adverse effect level dose in rats.

Reference Data of the Main Physiological Parameters in Control Sprague-Dawley Rats from Pre-clinical Toxicity Studies / 한국실험동물학회지

The purpose of this paper is to provide reference data related to the body weight, food & water consumptions, urinalysis, hematology and serum biochemistry parameters and absolute & relative organ weights obtained from control Sprague-Dawley rats, used in the 4-week and 13-week repeated-dose toxicity studies conducted in our laboratory between 2005 and 2008. The mean, standard deviation, minimum and maximum range values for hematology and serum biochemistry parameters, data of absolute & relative organ weights, and the difference between sexes and study duration of week 4 versus 13 week are presented. The studies were conducted according to "the standards of Toxicity Study for Medicinal Products" (2005) and The KFDA Notification No. 2000-63 'Good Laboratory Practice (GLP)' (2000) issued by KFDA. These data could be used as reference material of Sprague-Dawley rats by conducting the studies to evaluate the toxicological profile of pre-clinical toxicity studies.

Avaliação da toxicidade aguda e subaguda, em ratos, do extrato etanólico das folhas e do látex de Synadenium umbellatum Pax / Acute and subacute toxicity studies of the latex and of the ethanolic extract of the leaves of Synadenium umbellatum Pax in rats

O uso de plantas medicinais tem sido muito significativo nos últimos anos, sendo incentivado pela Organização Mundial de Saúde (OMS). Synadenium umbellatum Pax, Euphorbiacea (vulgo cola-nota, cancerola, milagrosa) tem o látex usado empiricamente como antitumoral e antiinflamatório. Por existir espécies tóxicas nesta família e visando à segurança no uso de extratos vegetais, tal estudo avaliou a toxicidade pré-clínica do látex e do extrato etanólico das folhas (EEF) de S. umbellatum, por via oral, em ratas Wistar. O estudo seguiu diretrizes do Guideline 423 (toxicidade aguda) e Guideline 407 (toxicidade subaguda) da OECD (Organisation for Economic Cooperation and Development). Na toxicidade aguda do látex e do EEF, não se observou letalidade nem alterações fisiológicas e comportamentais das ratas na dose de 2000 mg/kg, sendo praticamente atóxico. Porém, na análise histopatológica, o látex ocasionou congestão e infiltrado leucocitário nos rins, fígado e pulmões, efeitos não observados com o EEF. Na toxicidade subaguda, doses de 50, 100 e 200 mg/kg de EEF não produziram alterações dose-dependentes significativas nos parâmetros laboratoriais e fisiológicos, nem alterações macroscópicas e histopatológicas nos órgãos das ratas. Contudo, o uso crônico da planta S. umbellatum merece mais estudos.

The use of medicinal plants has been being very significant in the last years, being the use encouraged by WHO. Synadenium umbellatum Pax, Euphorbiacea (popularly known as cola-note, cancerola, miraculous) has the latex used empirically as anti-cancerous and anti-inflammatory. For there being toxic species in this family and aiming at the safety in the use of vegetable extracts, such study evaluated the pre-clinical toxicity of the latex and of the ethanolic extract of the leaves (EEL) of S. umbellatum, administrated by oral route, in Wistar female rats. The study followed OECD's Guidelines for test of acute toxicity (Guideline 423) and for subacute toxicity (Guideline 407). In the acute toxicity of latex and EEL, behavioral and physiological alterations were not observed neither animal's death in the dose level of 2,000 mg/kg. However, the latex caused congestion and leukocytes infiltration of the kidneys, liver and lungs, effects not observed with EEL. In the subacute toxicity, dose levels of 50, 100 and 200 mg/kg of EEL did not produced significant dose-dependent alterations in the lab results and no physiologic, macroscopic and hystopathological alterations. EEL of S. umbellatum is practically poisonless in acute exposure; already the latex can cause hystological damages. The chronic use of S. umbellatum needs more specific studies.

Estudo toxicológico pré-clínico agudo com o extrato hidroalcoólico das folhas de Cissus sicyoides L. (Vitaceae) / Acute pre-clinical toxicological study with the hydroalcoholic extract of the leaves of Cissus sicyoides L. (Vitaceae)

O estudo objetivou realizar ensaio toxicológico pré-clínico inicial para investigar a toxicidade da planta. Na investigação da DL50 foram utilizados grupos de camundongos Swiss machos (n = 10) submetidos a doses de 5,0 g/kg, via oral, e dose de 2,0 g/kg por via intraperitoneal, da fração aquosa das folhas (FAF) de Cissus sicyoides L. Foi retirado sangue através do plexo braquial após sete dias, para análise laboratorial de parâmetros hematológicos e bioquímicos. No estudo anatomopatológico, os animais foram examinados macro e microscopicamente, com ressecção de pulmão, coração, fígado e rins. Para análise dos dados foram utilizadas técnicas de estatística descritiva e inferencial. Na avaliação dos parâmetros hematológicos e bioquímicos dos camundongos Swiss, foram detectadas alterações nas transaminases AST e ALT e na fosfatase alcalina (FAL), caracterizando as alterações hepáticas demonstradas no estudo histopatológico. Na avaliação histológica do fígado de camundongos, evidenciou-se hepatite reacional com portite linfocitária crônica e lobular multifocal, hiperplasia kupferiana, colapsos focais da trama reticular, ausência de fibrose portal e lobular. O estudo toxicológico pré-clínico agudo demonstrou em camundongos alterações hepáticas.

The aim of the study was to carry through pre-clinical toxicological assay to analyze the toxicity of the plant. In the inquiry of the LD50 groups of male Swiss rats (n = 10) were given orally 5.0 g/kg, and 2.0 g/kg intraperitoneally, of the water fraction of the leaves (WFL) of Cissus sicyoides L. Blood was removed through brachial plexus after seven days, for laboratory analysis of hematological and biochemical parameters. In the anatomopathological study, the animals had been examined macro and microscopically, with dissection of lung, heart, liver and kidneys. For analysis of the data techniques of descriptive and inferencial statistics had been used. In the evaluation of the hematological and biochemical parameters of the Swiss rats, alterations in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (FAL) had been detected, characterizing the demonstrated hepatic alterations in the histopathological study. In the histological evaluation of the rats's liver, submitted to the poisoning, reactionary hepatitis with chronic linfocity portite was proven and to lobular multifocal, hiperplasia kupferiana, focal collapses of the reticular tram, absence of fibrosis, absences of cellular atipias and reactionary subcapsulite. The acute pre-clinical toxicological study demonstrated hepatic alterations in rats.