Repeated dose 90-day oral toxicity study of Vitex megapotamica (Spreng.) Moldenke.

Vitex megapotamica (Spreng.) Moldenke is a plant with medicinal properties popularly used in Brazil to treat diabetes and obesity. Despite the promising use of this plant, are still incipient toxicology studies on prolonged periods of treatment. The aim of this study was to evaluate the repeated dose 90-day oral toxicity study of V. megapotamica methanolic extract (VMME) in male and female Wistar rats. Different groups of rats (n = 8) were treated daily with three different doses of VMME (100, 300, and 900 mg/kg) or vehicle (filtered water). Body weight, water, and feed consumption, and clinical and behavioral changes were monitored daily. At the end of the experimental period, blood samples were obtained for hematological and biochemical analyzes. After euthanasia, the vital organs were removed for the determination of relative weight and for histopathological analysis. No clinical signs of toxicity or mortality were found during the experimental period. Treatment with VMME did not induce any change in body weight gain, eating patterns, and behavior. We found no statistically significant changes in the different hematological and biochemical parameters evaluated. The relative weight of the organs and histopathological analysis did not show any significant change when compared to animals treated with the vehicle. The data obtained in this study allow us to conclude that the VMME obtained from V. megapotamica is safe after a repeated-dose 90-day oral toxicity study in male and female Wistar rats.

Characterization of the Activity of Croton tiglium Oil in Hetter's Very Heavy Phenol-Croton Oil Chemical Peels.

BACKGROUND: Croton oil (CO) is used by dermatologists and plastic surgeons in deep chemical peels. It is mixed with phenol, water, and a soap in Baker-Gordon's or Hetter's formulas. There is controversy as to whether CO or phenol is the active agent in the dermal effect of deep chemical peels. OBJECTIVE: To better clarify the role of CO in deep peels, by identification of active compounds in commercially available CO in the United States and biological effects in vivo. MATERIALS AND METHODS: Liquid chromatography-tandem mass spectrometry on CO and a domestic pig model experiment using 3 different formulas: G1: 5% Septisol (SEP), G2: 1.6% croton oil in 35% phenol with 5% SEP, and G3: 35% phenol with 5% SEP. RESULTS: Liquid chromatography-tandem mass spectrometry indicated the presence of phorbol esters. G1 was null overall. Extent of the coagulative necrosis: G2 > G3. Vascular ectasia: G2 > G3. Inflammation pattern: intense neutrophilic inflammatory band in G2 versus mild, sparse, perivascular mononuclear cell infiltrate in G3. Neocollagenesis: pronounced in G2, negligible in G3. CONCLUSION: Coagulative necrosis of the epidermis, superficial fibroblasts, and vasculature can be attributed to the action of phenol. Phorbol esters on CO could be responsible for the dense deep acute inflammation and the distinctive neocollagenesis.

Genotoxicity Study of Vitex megapotamica (Spreng.) Moldenke.

Vitex megapotamica (Spreng) Moldenke is commonly known as tarumã, it is an important medicinal and edible fruit plant. It is native to regions of tropical and subtropical climate in greater proportion than temperate zones and widely distributed in Central America, South America, Asia, and Africa. In Brazil, it is present in the Atlantic Forest and Cerrado biomes. Despite its widespread use, there are no minimum standards for quality control or information on genotoxicity. Therefore, the aim of this study was to present a detailed description of the short-term genotoxicity assays of V. megapotamica and to provide parameters of a preparation routinely used in traditional folk medicine. For genotoxicity assays, five groups were used with eight wistar rats in each group. For this, three doses of the V. megapotamica extract in doses (100, 300, and 900 mg/kg) or negative control (filtered water) were administered orally and positive control cyclophosphamide monohydrate (20 mg/kg; Sigma-Aldrich®) was applied by the intraperitoneal route after 24 h. At the end, whole blood was collected in a tube containing EDTA for the comet test and later the animals were euthanized. For the micronucleus test, femurs were removed, and bone marrow was collected. In the comet assay, V. megapotamica crude extract did not show significant DNA damage at all doses tested. The micronucleus assay showed no significant increase in the frequency of inducing micronuclei at any dose examined. It can be concluded that the safety parameters in genotoxicity studies reveal that V. megapotamica has no toxicity, which characterizes the important quality control of this plant species.

Antiatherosclerotic Properties of Echinodorus grandiflorus (Cham. & Schltdl.) Micheli: From Antioxidant and Lipid-Lowering Effects to an Anti-Inflammatory Role.

Echinodorus grandiflorus is an important medicinal plant species that is native to South America. Despite extensive popular usage as a hypolipidemic drug, its effects as an atheroprotective agent remain unknown. The aim of this study was to evaluate the effects of an ethanol-soluble fraction that was obtained from E. grandiflorus (ESEG) leaves against the development of atherosclerosis in rabbits. Male rabbits received a diet that was supplemented with 1% cholesterol (cholesterol-rich diet [CRD]) for 60 days. After 30 days of the CRD, the animals were divided into five groups (n = 6) and treated with ESEG (10, 30, and 100 mg/kg), simvastatin (2.5 mg/kg), or vehicle once daily for 30 days. The negative control group was fed a cholesterol-free diet and treated orally with vehicle. At the end of 60 days, serum lipids, oxidized low-density lipoprotein, thiobarbituric acid reactive substances, nitrotyrosine, and serum interleukin 1 beta (IL-1ß), IL-6, soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) levels were determined. Samples from the aortic arch and thoracic segment were also collected to investigate the tissue antioxidant defense system and perform histopathological analysis. Oral ESEG administration significantly reduced serum lipid levels in CRD-fed rabbits. This treatment also modulated the arterial antioxidant defense system by reducing lipid and protein oxidation. Similarly, serum IL-1ß, IL-6, sICAM-1, and sVCAM-1 levels significantly decreased, accompanied by a reduction of atherosclerotic lesions in all arterial branches. These findings suggest that ESEG may be a new herbal medicine that can be directly applied for the treatment and prevention of atherosclerotic disease.

Heart-Protective Effects of Echinodorus grandiflorus in Rabbits That Are Fed a High-cholesterol Diet.

Excess weight and dyslipidemia are among the most serious health problems in Western societies. These conditions enhance the risk of cardiac disease and have been linked with a higher prevalence of cardiac arrhythmias and sudden death. The present study investigated the cardioprotective effects of Echinodorus grandiflorus on ventricular remodeling in rabbits that were fed a 1% cholesterol-rich diet. We first obtained an ethanol-soluble fraction of E. grandiflorus and performed a detailed phytochemical study by liquid chromatography-DAD/ESI-MS. For 60 days, male rabbits were fed the cholesterol-rich diet or a diet without the addition of cholesterol. After 30 days, different groups of rabbits were treated with the ethanol-soluble fraction of E. grandiflorus (10, 30, and 100 mg/kg, p. o.), simvastatin (2.5 mg/kg), or vehicle once daily for 30 days. At the end of 60 days, the serum lipoprotein ratio, electrocardiographic profile, histopathological alterations, and the cardiac antioxidant defense system were investigated. Echocardiographic analysis showed morphological and functional alterations in cholesterol-rich diet-fed animals, indicating left ventricle hypertrophy. The total cholesterol/high-density lipoprotein ratio and low-density lipoprotein/high-density lipoprotein ratio were significantly higher in cholesterol-rich diet-fed rabbits. Myocardial flaccidity, fatty degeneration, and concentric left ventricular hypertrophy were observed. An increase in lipid peroxidation levels, a decrease in superoxide dismutase activity, and a decrease in reduced glutathione levels were observed in the myocardium of all cholesterol-rich diet-fed rabbits. Treatment with the ethanol-soluble fraction of E. grandiflorus, especially the highest dose, significantly reduced all of these alterations, thus demonstrating the cardioprotective effect of the ethanol-soluble fraction of E. grandiflorus on cardiac changes that are induced by a cholesterol-rich diet.

90-Day Oral Toxicity Assessment of Tropaeolum majus L. in Rodents and Lagomorphs.

Tropaeolum majus L., popularly known as nasturtium, is a species widely used in the form of infusions and salads. In the last years, the antihypertensive, diuretic, and calcium and potassium sparing activities of T. majus preparations were shown. Moreover, no preclinical 90-day oral toxicity studies were conducted. Thus, this study evaluated the toxicity of the hydroethanolic extract obtained from T. majus (HETM) leaves in female and male mice, rats, and rabbits. Swiss mice and Wistar rats were treated with HETM (75, 375, and 750 mg/kg). The doses of rabbits (30, 150, and 300 mg/kg) were calculated by allometric extrapolation. The control groups received vehicle. The animals were orally treated, daily, for 90 days. At the end, the animals were anesthetized, and body weight gain, relative weight of liver, kidney, and spleen, and histopathological changes were evaluated. Serum hematological and biochemical parameters were also analyzed. No alterations were found in body and organ weights or in histopathological and biochemical evaluation. Hematological analyses revealed small changes in lymphocytes and neutrophil counts in rats after administration of 750 mg/kg of HETM. These results showed that 90-day use of T. majus is safe in rodents and lagomorphs.