Artemether-loaded polymeric lipid-core nanocapsules reduce cell viability and alter the antioxidant status of U-87 MG cells.

Glioblastomas are tumors that present a high mortality rate. Artemether (ART) is a lactone with antitumor properties, demonstrating low bioavailability and water solubility. In the present study, we developed lipid-core nanocapsules (LNC) containing pequi oil (Caryocar brasiliense Cambess) as the oily core for ART-loaded LNCs (LNCART) and evaluated their effect on human glioblastoma cells (U-87 MG). LNCs were developed by interfacial deposition of a preformed polymer, followed by physicochemical characterization. LNCART revealed a diameter of 0.216 µm, polydispersity index of 0.161, zeta potential of -12.0 mV, and a pH of 5.53. Furthermore, mitochondrial viability, proliferation, total antioxidant status, and antioxidant enzyme activity were evaluated. ART reduced cell viability after 24 h and proliferation after 48 h of treatment at concentrations equal to or above 40 µg . mL-1. LNCART, at 1.25 µg . mL-1, reduced these parameters after 24 h of treatment. Furthermore, superoxide dismutase (SOD) activity was elevated, while glutathione reductase (GR) activity was reduced. These findings suggest that ART loaded into LNC may be a promising alternative to improve its pharmacological action and possible application as a therapeutic agent for glioblastoma.

In vivo mutagenic effects and oxidative stress parameters evaluation of cypermethrin and benzoate of emamectin and their mixtures in female mice.

We evaluated the biological effects of ingestion by gavage, for 28 days, of the pesticides cypermethrin (CP) and emamectin benzoate (EB) and their mixtures in female Swiss mice. The groups were Control (water); CP; EB and three distinct concentrations of CP and EB mixture expressed in mg/kg/day. The biological effects were analyzed in the complete blood count and plasma (alkaline phosphatase (ALP), alanine aminotransferase (ALT) and creatinine); the biochemical parameters of oxidative stress (substances reactive to thiobarbituric acid (TBARS); reduced glutathione (GSH); catalase (CAT), superoxide dismutase (SOD) and glutathione-S-transferase (GST)), and bone marrow cells obtained from the femur for the micronucleus (MN) test. In the heart, there was a reduction in GSH in the groups (0.5 + 0.67 and 2.5 + 3.37), although in the brain this effect appeared for the other groups, except EB. Brain TBARS increased in CP and in the group (2.5 + 3.37) and platelets increased in the group (12.5 + 16.87). Genotoxic/mutagenic effects, showing a consistent increase dose-dependent effect on micronucleus counting for in the female mice. After 28 days of treatment, we can observe that the pesticide mixtures promoted genotoxic damage and oxidative brain damage in female mice, which can damage the health of these animals and possibly their future offspring.

Influence of biochar on the sorption and leaching of thiamethoxan in soil.

This study evaluated the long-term effect of biochar application on the sorption and desorption of thiamethoxam in a Haplic Plinthosol. The experiment was conducted in a randomized block design with combination of doses of mineral fertilizer NPK (0 and 300 kg·ha-1 formula 05-25-15) and biochar (0, 16 and 32 Mg ha-1). Deformed soil samples were collected in the field from the 0-0.10 m layer of all plots to determine the sorption and desorption of the thiamethoxam insecticide in the soil; fulvic acid (FA), humic acid (AH) and humin (HUM) carbon contents; and total organic carbon. The Batch slurry method was used to evaluate sorption and desorption. The Freundlich isotherm adequately described thiamethoxam sorption in all treatments. The application of biochar increased the sorption (Kfs) and decreased the desorption (Kfd) of thiamethoxam. The sorption intensity (1/n) showed reduction characteristics as the soil concentration of thiamethoxam increased. Biochar has a sorption effect on the soil through covalent bonds and H-bonds with the insecticide molecules, thereby indirectly increasing the sorption potential in the chemical fractions of the organic matter of soil. The application of 32 Mg ha-1 of biochar significantly reduced thiamethoxam in the soil solution. Altogether, the present study reveals that biochar application in soil is a promising tool for mitigating the contaminant potential of thiamethoxam in subsurface waters.

Effects of the acute exposition to glyphosate-based herbicide on oxidative stress parameters and antioxidant responses in a hybrid Amazon fish surubim (Pseudoplatystoma sp).

The aim of this study was to investigate the effects of acute glyphosate (active ingredient) exposure on the oxidative stress biomarkers and antioxidant defenses of a hybrid surubim (Pseudoplatystoma sp). The fish were exposed to different herbicide concentrations for 96 h. The thiobarbituric acid-reactive substances (TBARS), protein carbonyls and antioxidant responses were verified. The 15 mg a.pL(-1) of herbicide resulted in the death of 50% of the fish after 96 h. An increase in liver and muscle TBARS levels was observed when fish were exposed to the herbicide. The protein carbonyl content was also increased in the liver (4.5mg a.pL(-1) concentration) and brain (2.25 mg a.pL(-1) concentration). The antioxidant activities decreased in the liver and brain after exposure to herbicide. Levels of ascorbic acid in the liver (2.25 mg a.pL(-1) and 4.5 mg a.pL(-1) concentrations) and brain (2.25 mg a.pL(-1) concentration) were increased post-treatment. Levels of total thiols were increased in the liver and brain (2.25 mg L(-1) and 7.5mg a.pL(-1), respectively). Glyphosate exposure, at the tested concentrations affects surubim health by promoting changes that can affect their survival in natural environment. Some parameters as TBARS and protein carbonyl could be early biomarkers for Roundup exposure in this fish species.

Characterization and quantification of the compounds of the ethanolic extract from Caesalpinia ferrea stem bark and evaluation of their mutagenic activity.

Caesalpinia ferrea Martius has traditionally been used in Brazil for many medicinal purposes, such as the treatment of bronchitis, diabetes and wounds. Despite its use as a medicinal plant, there is still no data regarding the genotoxic effect of the stem bark. This present work aims to assess the qualitative and quantitative profiles of the ethanolic extract from the stem bark of C. ferrea and to evaluate its mutagenic activity, using a Salmonella/microsome assay for this species. As a result, a total of twenty compounds were identified by Flow Injection Analysis Electrospray Ionization Ion Trap Mass Spectrometry (FIA-ESI-IT-MS/MSn) in the ethanolic extract from the stem bark of C. ferrea. Hydrolyzable tannins predominated, principally gallic acid derivatives. The HPLC-DAD method was developed for rapid quantification of six gallic acid compounds and ellagic acid derivatives. C. ferrea is widely used in Brazil, and the absence of any mutagenic effect in the Salmonella/microsome assay is important for pharmacological purposes and the safe use of this plant.

Effect of Liposomal Protium heptaphyllum (Alb.) March Extract in the Treatment of Obesity Induced by High-Calorie Diet.

Obesity, a chronic disease, resulted from excessive consumption of high-calorie foods, leading to an energy imbalance. Protium heptaphyllum (P. heptaphyllum) was used in folk medicine for its analgesic, anti-inflammatory, and healing properties. The association of the extract from P. heptaphyllum with nanotechnology was innovative for combining high technology with active ingredients that are easily accessible in the Amazon region. This study evaluated the effect of liposomes containing the ethyl acetate fraction of the crude extract of P. heptaphyllum leaves on obesity. Male Wistar rats treated with a high-calorie diet for 8 weeks to induce obesity received treatment with the liposome formulation containing P. heptaphyllum extract (1 mg/kg/day, via gavage) for 14 days. Morphological, metabolic, redox status, immunological, and histological parameters were evaluated in the adipose and liver tissue of the animals. The groups were divided as follows: C: control; P: liposomes containing extract; O: obese, and OP: obese + liposomes containing extract. The obesity model resulted in increases in body weight, caloric intake, body fat weight, and in the lipid profile. In adipose tissue, P decreased SOD (superoxide dismutase) activity in obese animals. In the liver, a positive modulation of the extract was observed in relation to glucose, amino acids, lactate, hepatoprotective action, and anti-inflammatory activity, with a decrease in interleukin 1ß (IL-1ß) in obese animals. The results showed an improvement in the functional and inflammatory aspects, but the treatment was not effective in alleviating general changes related to obesity, such as weight gain, fat, glucose, triglycerides, and inflammation in adipose tissue, highlighting the complexity of responses in different organs during obesity and treatment with P. heptaphyllum.

Study of Liposomes Containing Extract from the Leaves of Protium heptaphyllum (Aubl.) March in Animals Submitted to a Mutagenic Model Induced by Cyclophosphamide.

Cyclophosphamide (CPA) is an alkylating agent used as a chemotherapy agent in the treatment of cancer, but it has immunosuppressive effects. Protium heptaphyllum (P. heptaphyllum) is a plant rich in triterpenes and flavonoids, with some bioactive and therapeutic properties presented in the literature. Thus, the present study aimed to investigate the chemoprotective potential of P. heptaphyllum extract inserted into liposomes against oxidative damage chemically induced by CPA. Male Swiss mice received 1.5 mg/kg of P. heptaphyllum liposomes as a pre-treatment for 14 consecutive days (via gavage) and 100 mg/kg of CPA in a single dose (via intraperitoneal) on the 15th day. After the experimental period, blood and organ samples were collected for histopathological and biochemical analyses, including superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione S-transferase (GST), reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS), ascorbic acid (ASA), carbonyl protein, cytokine measurement, and micronucleus testing. The results showed that liposomes containing P. heptaphyllum extract have an antimutagenic effect against damage induced to DNA by CPA, and that they also protect against oxidative stress, as verified by the increase in the antioxidant enzymes SOD and GPx. The improvement in alkaline phosphatase and creatinine markers suggests a beneficial effect on the liver and kidneys, respectively. However, the depletion of GSH in the liver and brain suggests the use of antioxidants for the metabolism of molecules generated in these tissues. In general, these data show good prospects for the use of P. heptaphyllum liposomes as a cancer chemoprotective agent, as well as possible antioxidant action, conceivably attributed to the flavonoids present in the plant extract.

Vasoconstrictor and hemodynamic effects of a methanolic extract from Rhinella marina toad poison.

Rhinella marina toad is abundant in Brazil. Its poison contains cardiac glycosides called bufadienolides, which are extensively investigated for their bioactivity. Our aim was to characterize the vasoactivity of Rhinella marina poison (RmP) on the aorta of male Wistar rats. For this, the RmP was first collected and processed to obtain an alcoholic extract. To determine cardiovascular effects of RmP, we performed in vivo tests by administering RmP intravenously in doses of 0.1-0.8 mg/kg. Vascular reactivity was also performed through concentration-response curves to RmP (10 ng/mL to 200 µg/mL) in aortic segments with and without endothelium. RmP induced a concentration-dependent contraction in rat aorta which was partly endothelium-mediated. Nitric oxide contributes with this response in view that incubation with L-NAME increased the contractile response. Additionally, treatment with indomethacin [cyclooxygenase, (COX) inhibitor], nifedipine (L-type voltage-gated calcium channels blocker), and BQ-123 (ETA receptors antagonist) decreased maximum response, and ketanserin (5-HT2 receptors antagonist) decreased pEC50, suggesting active participation of these pathways in the contractile response. On the other hand, apocynin (NADPH oxidase inhibitor) did not alter contractility. Incubation with prazosin (α1-adrenergic receptor antagonist) abolished the contractile response, suggesting that the RmP-induced contraction is dependent on the adrenergic pathway. In the Na+/K+ ATPase protocol, a higher Emax was observed in the RmP experimental group, suggesting that RmP potentiated Na+/K+ATPase hyperpolarizing response. When this extract was injected (i.v.) in vivo, increase in blood pressure and decrease in heart rate were observed. The results were immediate and transitory, and occurred in a dose-dependent manner. Overall, these data suggest that the poison extract of R. marina toad has an important vasoconstrictor action and subsequent vasopressor effects, and its use can be investigated to some cardiovascular disorders.

Chemical profile of the parotoid gland secretion of the Amazonian toad (Rhinella margaritifera).

The secreted poisonin bufonids (Anura: Bufonidae) include proteins, biogenic amines, toxic bufadienolides and alkaloids. The chemical composition of the methanolic extract of parotoid gland secretions by the Amazonian toad Rhinella margaritifera was evaluated in a UFLC-DAD-micrOTOF system. Of the twenty three compounds found in the methanolic extract, eighteen were identified by the mass/charge ratio as: five arginine diacids, six bufagenins (telocinobufagin, marinobufagin, bufotalin, cinobufotalin, bufalin and cinobufagin), six bufotoxins, and an alkaloid (dehydrobufotenin).

Comparative study of the chemical profile of the parotoid gland secretions from Rhaebo guttatus from different regions of the Brazilian Amazon.

Amphibian cutaneous secretion has great potential for bioprospection and is a great tool in the development of bioproducts. Thus, the objective of the present work was to evaluate the comparative study of the chemical profile parotoid gland secretions from Rhaebo guttatus collected in two distinct regions of the Brazilian Amazon. For this, the chemical composition of six methanolic extracts of this species were analyzed by Liquid Chromatography in UV and MS Detection Ultra-Chromatography Systems (UFLC-DAD-micrOTOF). All obtained chromatograms presented two distinct regions; one referring to the more hydrophilic molecules (alkaloids), while the other refers to the more hydrophobic compounds (steroids). The steroid region resembles all samples, regardless of where they were collected. In the alkaloid region, there was a standardized variation for the samples from the southern Brazilian Amazon, but the same was not true for the samples collected in the Amazon-Cerrado transition region. Thus, the data suggest that the environment and diet of R. guttatus may be important in alkaloid production, but do not influence steroid content. These results add new information about the poison of the toad R. guttatus and raises new questions to be further investigated, thus contributing to the knowledge of the anuran fauna of the Brazilian Amazon.

Healing of dermal wounds property of Caryocar brasiliense oil loaded polymeric lipid-core nanocapsules: formulation and in vivo evaluation.

Cutaneous lesions lead to complications in patients, since they may be recurrent and also represent risk of progression to infection and/or amputation. Therefore, effective, protective, and topical treatments of easy application and removal need to be developed to provide effective alternatives to patients. The Caryocar brasiliense Cambess (CBC) presents important pharmacological activities and proved in the healing process. This paper reports the improvement of the CBC nanostructured (LNCCBC and LNCCBC+) activity in dermal wounds in vivo. The oil was physico-chemically characterized and used in the development of lipid-core nanocapsules (LNCs), coated (LNCCBC+) or without chitosan (LNCCBC), in concentration of 1.0 mg mL-1. Hydrogel (HG) was tested in vivo on lesions in the back of male Wistar rats for 14 days. The oil presented appropriate physico-chemical characteristics for its use, such as moisture 0.76 %, acidity 0.85 % and oleic acid 25.90 %. The LNCs showed nanometric size (around 200 nm), monomodal distribution, slight acid pH and zeta potential of + 22.1 mV in accordance with the composition. The nanostructured oil induced dermal healing in vivo showing significantly better improvement than free oil. LNCCBC+ showed best results showing the higher increase of the production of type 1 collagen, an important protein to the healing repair. These results suggest that development of formulations LNCCBC and LNCCBC+ are promising and important alternative for the treatment of dermal wounds, avoiding complications related to cutaneous lesions.

Investigation of crude methanolic extract from poison secreted by the Rhaebo gutattus on status redox antioxidant in mice

The study evaluated the antioxidant properties of a crude methanolic extract (CME) from Rhaebo guttatus poison in mice over a period of 7 and 30 days. The mice were divided into groups and treated with different concentrations of the extract (0; 8 µg mL-1; 16 µg mL-1 and 32 µg mL-1 or vehicle; 100 µL/animal/day; via gavage). The liver samples were analyzed for status redox parameters as catalase (CAT), glutathione-S-transferase (GST), reduced glutathione (GSH) and thiobarbituric acid reactive substances (TBARS). The results showed that the CME caused changes in the levels of various antioxidants and oxidative stress markers. At 7 days, there was an increase in TBARS levels (8 µg mL-1 dose) and GST activity (16 µg mL-1 dose), and a reduction in GSH levels (32 µg mL-1 dose) compared to the control group. At 30 days, TBARS and GSH levels returned to control values in the same period, but GSH increased (32 µg mL-1 dose) compared at 7 days; GST activity remained high after 30 days for 32 µg mL-1 dose compared other groups and time of treatment (7 days). Overall, the study suggests that the extract modulates antioxidant properties per se that can affect various markers of status redox in the liver of mice, mainly 16 µg mL-1 dose demonstrated to act under antioxidant enzymes in different times (7 or 30 days).

Investigation of antioxidant activity of ethanolic extract of the bark of Caesalpinia ferrea in Swiss mice exposed to paracetamol / Investigação da atividade antioxidante do extrato etanólico da casca de Caesalpinia ferrea em camundongos Swiss expostos ao paracetamol

Aims: it was evaluated the antioxidant effect of the ethanolic extract of Caesal-pinia ferrea bark in a model of oxidative stress induced by paracetamol (PCM). Methods: male Swiss mice were subdivided into four groups (control; PCM; PCM+extract; extract; n=8) in which a dose of paracetamol (250 mg.kg-1) was administered and after 3 hours the treatment with the extract (100 mg.kg-1/day) was administered for seven days, via gavage. Oxidative stress biomarkers were determined, such as catalase, glutathione-S-transferase, reduced gluta-thione, ascorbic acid, thiobarbituric acid reactive substances and carbonylated proteins of liver, kidneys and brain and plasma parameters through the dosage of glucose, cholesterol, triglycerides, aspartate aminotransferase and alanine aminotransferase. Results: the Caesalpinia ferrea extract was able to reverse the lipid and protein damage caused by the drug in the liver tissue and caused the same effect in the renal and brain tissues in the carbonylated proteins. The extract alone decreased liver glutathione-S-transferase and increased catalase and brain glutathione-S-transferase activity, in addition to lowering glucose and cholesterol, but without altering the triglycerides. Conclusions: it was possible to conclude that the ethanolic extract of the bark of Caesalpinia ferrea has a good antioxidant activity, probably due to dose of paracetamol in the samples investigated. However, more studies are needed for a better understanding of the effects of this extract compared to the effects found in this research

Objetivos: foi avaliado o efeito antioxidante do extrato etanólico da casca de Caesalpinia ferrea em modelo de estresse oxidativo induzido por paracetamol (acetaminofeno, PCM). Métodos: camundongos Swiss machos foram subdivididos em quatro grupos (controle; PCM; PCM+extrato; extrato; n=8) nos quais foi administrada uma dose de paracetamol (250 mg.kg-1) e após três horas foi administrado o tratamento com o extrato (100 mg.kg-1/ dia) por sete dias, via gavagem. Foram determinados biomarcadores de estresse oxidativo, como catalase, glutationa-S-transferase, glutationa reduzida, ácido ascórbico, substâncias reativas ao ácido tiobarbitúrico e proteínas carboniladas do fígado, rins e cérebro, além de parâmetros plasmáticos através da dosagem de glicose, colesterol, triglicerídeos, aspartato aminotransferase e alanina aminotransferase. Resultados: o extrato de Caesalpinia ferrea foi capaz de reverter os danos lipídicos e proteicos causados pela droga no tecido hepático, e também causou o mesmo efeito nos tecidos renal e cerebral nas proteínas carboniladas. O extrato sozinho diminuiu a atividade da glutationa-S-transferase hepática e aumentou a da catalase e glutationa-S-transferase cerebral, além de diminuir a glicose e o colesterol, mas sem alterar os triglicerídeos. Conclusões: foi possível concluir que o extrato etanólico da casca de Caesalpinia ferrea apresenta uma boa atividade antioxidante, provavelmente devido à presença de taninos, tendo em vista os danos causados pela alta dose de paracetamol nas amostras investigadas. Entretanto, mais estudos são necessários para um melhor entendimento dos efeitos deste extrato frente aos efeitos encontrados nesta pesquisa

Acute toxicity and effects of Roundup Original® on pintado da Amazônia.

The toxicity of Roundup Original® (GLY), a glyphosate-based herbicide widely used in crops in Mato Grosso state, was determined in hybrid fish jundiara or pintado da Amazônia. The 96 h-LC50 of GLY was 13.57 mg L-1. Moreover, exposure to sublethal concentrations of GLY (0, 0.37, 0.75, 2.25, 4.5, 7.5 mg L-1) has not altered the survival rate (100% for all treatments). In fish liver, protein carbonyl (PC) levels as well as glutathione-S-transferase (GST) activity, reduced glutathione (GSH), and ascorbic acid (ASA) contents increased when compared to control group. Superoxide dismutase (SOD) activity was reduced and catalase (CAT) has not changed. PC content has grown in muscle and brain, and thiobarbituric acid-reactive species (TBARS) levels also increased in muscle, but in the brain, they remained unaltered. Acetylcholinesterase (AChE) activity reduced in muscle but increased in brain when compared to control group. Our results suggest that short-term exposure to GLY induced alterations in the oxidative stress biomarkers in fish and can be interfering with their survival in natural environment; besides, these findings may be considered of high ecotoxicological relevance.

Oxidative stress in the hybrid fish jundiara (Leiarius marmoratus × Pseudoplatystoma reticulatum) exposed to Roundup Original®.

The aim of this study was to investigate the effects of Roundup Original®, a glyphosate-based herbicide, against biochemical parameters including thiobarbituric acid-reactive substances (TBARS), protein carbonyl, enzymatic and nonenzymatic antioxidant responses and acetylcholinesterase (AChE) of jundiara fish (Leiarius marmoratus × Pseudoplatystoma reticulatum) at a sublethal concentration of 1.357 mg L-1. Fish exposed to the herbicide for different periods (6-96 h) showed a significant increase of both hepatic and muscular TBARS and protein carbonyl. Enzymatic antioxidant activity was decreased in the liver and brain after 48 h of exposure. Glutathione-S-tranferase (GST) had its levels raised in the brain and gills, probably as a toxicity event response. Non protein thiols (GSH) demonstrated a reduction after 6 and 24 h of exposure in the hepatic tissue, followed by an increase at 48 and 96 h in the same tissue. GSH brain levels, however, increased only after 96 h. AChE activity in muscle decreased for all the times tested (26.5, 45, 38 and 14% for 6, 24, 48 and 96 h respectively), but only at 96 h (34%) in the brain. We found that Roundup Original® is able to trigger important changes in the biochemical parameters tested, showing it can be a potential threat for the health and survival of fish in the environment.

Effects of glyphosate-based herbicide on pintado da Amazônia: Hematology, histological aspects, metabolic parameters and genotoxic potential.

Roundup Original® is an herbicide widely used in Mato Grosso's agriculture and it may contamine water bodies, being an unforeseen xenobiotic to aquatic organisms, particularly fish. This study investigated the effects on the hybrid fish jundiara (Leiarius marmoratus×Pseudoplatystoma reticulatum) of an environmentally relevant exposure to this herbicide. Glucose levels in liver, muscle and plasma decreased after exposure to 1.357mgL-1 of Roundup Original® (glyphosate nominal concentration), while glycogen levels reduced in liver and muscle for different times. Elevated cholesterol and triglycerides revealed an adaptive response. Protein and lactate levels also increased during the experiment, however no changes were observed for muscle lactate. Increment of the transaminases suggests damage to the liver cells. After 96hours of exposure, reductions in all hematological parameters were observed, whereas the micronucleus test findings showed genotoxic scenery. Histological analysis did not display pathological alterations of the hepatic tissue. The results obtained provide valuable data for noticing the effects of pollutants on non-target organisms.

Investigation of the possible protective effect of Smilax fluminensis steud. leaf in mice subjected to oxidative stress by paracetamol

Paracetamol (PCM) is a drug widely used by the population as an antipyretic and analgesic. If administered in high doses it can cause liver damage, leading to hepatoxicity. The genus Smilax, found in temperate and tropical regions, is traditionally used by the population through the extract of leaves and roots for several conditions, such as in the treatment of syphilis, diabetes, asthma and as a diuretic action. Through this, Smilax fluminensis leaf extracts were used to evaluate the protective effect against oxidative stress induced by a high dose of PCM in mice that received the drug and after receiving treatment with crude extract and fractions. Plasma analysis was performed using as partate aminotransferase (AST), alanine aminotransferase (ALT), glucose, triglycerides and cholesterol, in addition to biochemical techniques such as catalase (CAT), glutathione-S-transferase (GST), reduced glutathione (GSH), ascorbic acid (ASA), substances reactive to thiobarbituric acid (TBARS) and carbonylated proteins (CARBONYL) of liver, brain and kidneys. Fraction 1 of the extract was the most promising, decreasing the plasma levels of AST and ALT, the levels of CAT and GST of the liver, together with GSH and in the renal and brain tissue there was a decrease in carbonylated proteins (PCM + F1 versus PCM ). Besides, fraction 1 proved to be hypoglycemic and hypocholesterolemic. It is concluded that fraction 1 of Smilax fluminensis leaves has good antioxidant activity in the face of the damage caused by the high dose of paracetamol.

First phytochemical study and biological activity of the leaves ethanolic extract from Cissus spinosa Cambess / Primeiro estudo fitoquímico e atividade biológica do extrato etanólico de folhas de Cissus spinosa Cambess

Aims: The objective of this study was to identify the phytochemical profile and to evaluate the biological effects of the crude ethanolic extract (EE) and the ethanolic fraction (EF) of leaves of the species Cissus spinosa Cambess, after oxidative stress induced by cyclophosphamide (CP) in mice. Methods: Phytochemical profile was performed detecting functional groups and, analysis of total flavonoids and phenols concentration, as well as the antiradical activity in EE and EF. The phytochemical characterization was done for the identification of flavonoids present in the leaves of the plant. In the biochemical tests, hematological parameters, glucose, total cholesterol, creatinine, alkaline phosphatase and aminotransferases dosages in plasma, enzymatic and non--enzymatic antioxidants and lipid damage marker were evaluated in different tissues (liver, kidney and heart), besides genotoxic and immunological analyzes. The animals received 15 days of treatment, via gavage, with EE (50 mg kg-1) or EF (50 mg kg-1) and on the 15th day, an intraperitoneal injection of CP (100 mg kg-1) or saline (0.9%). After 24 h the last treatment, the animals were anesthetized for blood withdrawal, sacrificed and removal of the organs. Results: In the phytochemical analyzes, the presence of alkaloids, flavonoids and phenols was identified, the latter presented a higher concentration for EF. Eight flavonoids were identified - Rutin, Quercetin-3-ß-D-glucoside, Quercitrin, Taxifolin, Quercetin, Canferol, Luteolin and Apigenin. In the biochemical analyzes, in general, EE showed a better antioxidant action against oxidative damages, hypoglycemic and antitilipemic action when comparing with EF, probably due to the synergism caused by flavonoids. It was observed the reduction and an increase of micronucleated polychromatic erythrocytes, due to the action of antioxidant compounds and alkaloids present in the plant, also considering the question of the seasonal period that directly interferes in the production of these compounds. In the immunological analysis, the extracts did not stimulate the spontaneous production of oxygen peroxide (H2 O2) and nitric oxide (NO•). Conclusions: Other studies, such as the variation of the chemical composition of the plant by local seasonality, hypoglycemic and antilipemic action, should be carried out to better delineate the biological action present in this plant.

Objetivos: O objetivo deste estudo foi identificar o perfil fitoquímico e avaliar os efeitos biológicos do extrato etanólico bruto (EE) e da fração etanólica (EF) das folhas da espécie Cissus spinosa Cambess, após estresse oxidativo induzido pela ciclofosfamida. (CP) em camundongos. Métodos: O perfil fitoquímico foi realizado detectando grupos funcionais e, análise da concentração de flavonoides e fenóis totais, bem como a atividade antirradical em EE e EF. A caracterização fitoquímica foi realizada para a identificação de flavonoides presentes nas folhas da planta. Nos testes bioquímicos, os parâmetros hematológicos, as dosagens de glicose, colesterol total, creatinina, fosfatase alcalina e aminotransferases no plasma, os antioxidantes enzimáticos e não enzimáticos e o marcador de dano lipídico foram avaliados em diferentes tecidos (fígado, rim e coração), além de análises genotóxicas e imunológicas. Os animais receberam 15 dias de tratamento, via gavagem, com EE (50 mg kg-1) ou EF (50 mg kg-1) e no 15º dia, injeção intraperitoneal de CP (100 mg kg-1) ou soro fisiológico (0,9%) . Após 24 h do último tratamento, os animais foram anestesiados para retirada do sangue, sacrificados e após a retirada dos órgãos. Resultados: Nas análises fitoquímicas, identificou-se a presença de alcaloides, flavonoides e fenóis, estes últimos apresentaram maior concentração para EF. Oito flavonoides foram identificados - rutina, quercetina-3-ß--D-glicosídeo, quercitrina, taxifolina, quercetina, canferol, luteolina e apigenina. Nas análises bioquímicas, em geral, o EE apresentou melhor ação antioxidante contra os danos oxidativos, ação hipoglicemiante e antitilipêmica quando comparada à EF, provavelmente devido ao sinergismo causado pelos flavonoides. Observou-se a redução e um aumento de eritrócitos policromáticos micronucleados, devido à ação de compostos antioxidantes e alcaloides presentes na planta, considerando também a questão do período sazonal que interfere diretamente na produção desses compostos. Na análise imunológica, os extratos não estimularam a produção espontânea de peróxido de oxigênio (H2O2) e óxido nítrico (NO•). Conclusões: Outros estudos, como a variação da composição química da planta por sazonalidade local, ação hipoglicemiante e antilipêmica, devem ser realizados para melhor delineamento da ação biológica presente nesta planta.

Antioxidant potential of Carica papaya Linn (Caricaceae) leaf extract in mice with cyclophosphamide induced oxidative stress / Potencial antioxidante do extrato de folhas de Carica papaya Linn (Caricaceae) em camundongos com estresse oxidativo induzido por ciclofosfamida

AIMS: This study aimed to investigate the effects of crude extract of Carica papaya leaves on oxidative stress in mice induced by cyclophosphamide, as well as phytochemical profile characterization of this extract. METHODS: The male Swiss mice received 15 days of treatment with the extract (500 mg kg-1, via gavage) and intraperitoneal injection of cyclophosphamide (75 mg kg-1) or saline (0.9%) on the 15th day. After 24 h the last treatment, the animals were anesthetized for blood withdrawal, sacrificed and removal of the organs for analyses (liver, kidney and heart). In the biochemical tests were determined: hematological parameters in blood, aminotransferases, alkaline phosphatase, glucose and total cholesterol dosages in plasma, enzymatic and non-enzymatic antioxidants and lipid damage marker were evaluated in different tissues, besides genotoxic and histopathological analyzes. RESULTS: In the extract of Carica papaya leaves, the flavonoids quercetin-3ß-D-glucoside and rutin were identified, besides present positive results for alkaloids, saponins and tannins. This extract increased the activity of glutathione-S-transferase and catalase enzymes in the liver and reduced the levels of reduced glutathione in the kidneys and hematocrit levels, red cell count, and hemoglobin. It promoted the decrease of the reactive species of thiobarbituric acid (TBARS) in the kidneys and the activity of enzyme aspartate aminotransferase in the plasma and was antimutagenic in the micronucleus test. CONCLUSIONS: The study showed that extract of Carica papaya was beneficial against oxidative events and prevented DNA damage. The extract also showed hepatotoxicity, therefore prolonged infusion of papaya leaves is not advisable.

OBJETIVOS: O objetivo deste estudo foi investigar os efeitos do extrato bruto de folhas de Carica papaya sobre o estresse oxidativo em camundongos induzidos pela ciclofosfamida, bem como a caracterização do perfil fitoquímico deste extrato. MÉTODOS: Os camundongos Swiss machos receberam 15 dias de tratamento com o extrato (500 mg kg-1, via gavagem) e injeção intraperitoneal de ciclofos-famida (75 mg kg-1) ou salina (0,9%) no 15º dia. Após 24 h do último tratamento, os animais foram anestesiados para retirada do sangue, sacrificados e retirada dos órgãos para análises (fígado, rim e coração). Nos testes bioquímicos foram determinados: parâmetros hematológicos em sangue, aminotransferases, fosfatase alcalina, dosagens de glicose e colesterol total no plasma, antioxidantes enzimáticos e não enzimáticos e marcador de dano lipídico foram avaliados em diferentes tecidos, além de análises genotóxicas e histopatológicas. RESULTADOS: No extrato de folhas de Carica papaya foram identificados os flavonoides quercetina-3ß-D-glicosídeo e rutina, além de resultados positivos para alcaloides, saponinas e taninos. Este extrato aumentou a atividade das enzimas glutationa-S-transferase e catalase no fígado e diminuiu os níveis de glutationa reduzida nos rins, a concentração do hematócrito, a contagem dos glóbulos vermelhos e a hemoglobina. Promoveu a diminuição das espécies reativas de ácido tiobarbitúrico (TBARS) nos rins, a atividade da enzima aspartato aminotransferase no plasma e foi antimuta-gênico no teste do micronúcleo. CONCLUSÕES: O estudo mostrou que o extrato de Carica papaya foi benéfico contra eventos oxidativos e preveniu danos no DNA. O extrato também mostrou hepatotoxicidade, portanto, a infusão prolongada de folhas de mamão não é aconselhável.

Evaluation of the antioxidant potential of Copaifera multijuga in Ehrlich tumor-bearing mice

Copaifera multijuga, commonly known as copaiba, is popularly used in the form of tea for various conditions due to the presence of antioxidant substances in its composition, which protect cells against damage caused by free radicals. Its oleoresin is also used as an anti-inflammatory and antitumoral agent. The present study investigated the antioxidant effect of the ethanolic extract of copaiba stem bark on Swiss mice inoculated with solid Ehrlich tumors. Mice were inoculated subcutaneously with 1x106 Ehrlich's tumor cells and treated via gavage with ethanolic extract of copaiba for thirty days, with doses varying between 100 and 200 mg kg-1. Biochemical analyses of enzymatic antioxidants [superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST)], non-enzymatic antioxidants [reduced glutathione (GSH) and ascorbic acid (ASA)], substances reactive to thiobarbituric acid (TBARS) and protein carbonylation (carbonyl) in different tissues were significantly affected. The extract administered at 200 mg kg-1 presented higher antioxidant capacity in the liver, increased CAT, GST, GSH and decreased TBARS, as well as increased CAT activity and protein carbonylation in brain tissue. The results showed that the copaiba extract was able to reverse the oxidative stress caused by solid Ehrlich tumor, probably due to the presence of antioxidant compounds, and had potential antineoplasic effect after a 30-day treatment. (AU)