ABSTRACT
Pelas características anatômicas e fisiológicas dos rins, a lesão renal aguda tem sua origem nefrotóxica pela alta circulação local, o que favorece a alta concentração de substâncias tóxicas e seus metabólitos no tecido. A lesão renal aguda é uma complicação comum em internações hospitalares e principalmente em internações em unidades de terapia intensiva. A ciclofosfamida, um quimioterápico utilizado no tratamento de doenças autoimunes e neoplasias sólidas, pode causar nefrotoxicidade com disfunção glomerular e tubular. O uso de plantas medicinais, pelas suas potentes ações antioxidantes, tem sido usado para prevenção ou tratamento de lesões celulares induzidas pelo desequilíbrio entre enzimas antioxidantes e oxidantes. Por esse motivo, o objetivo do experimento foi avaliar o potencial efeito protetor da Echinodorus grandiflorus na prevenção da nefrotoxidade induzida pela ciclofosfamida. Para isso, foi realizado o experimento com a utilização de 35 ratos machos, Wistar, divididos em seis grupos experimentais, sendo administrado a ciclofosfamida na dose de 150mg/kg nos grupos G2 a G6 e diferentes doses da Echinodorus grandiflorus, com posterior análise de parâmetros sanguíneos e histológicos. A administração de ciclofosfamida na dose de 150mg/kg de massa corporal, em dose única, foi capaz de induzir a nefrotoxicidade aguda em todos os ratos. O extrato bruto de Echinodorus grandiflorus apresentou potencial efeito renoprotetor ao uso da ciclofosfamida, na dose de 300mg/kg de massa corporal, sendo possível observar redução dos efeitos nefrotóxicos do quimioterápico, pela redução dos danos tubulares e pela diminuição dos espaços capsulas, nitidamente encontradas alterados no grupo que recebeu apenas ciclofosfamida, denotando resultados promissores para utilização desta planta medicinal na prevenção da nefrotoxicidade induzida pelo fármaco. Contudo, novos estudos dos efeitos renoprotetor do chapéu de couro, poderão elucidar os mecanismos envolvidos na ação do extrato bruto do chapéu de couro. A utilização de extrato bruto de plantas medicinais torna-se um adjuvante aos tratamentos pelo baixo custo e pela facilidade de acesso das diferentes populações as plantas desde que devidamente orientados pelos profissionais habilitados.
Due to the anatomical and physiological characteristics of the kidneys, acute kidney injury has its nephrotoxic origin due to the high local circulation, which favors the high concentration of toxic substances and their metabolites in the tissue. Acute kidney injury is a common complication in hospital admissions and especially in intensive care unit admissions. Cyclophosphamide, a chemotherapy drug used in the treatment of autoimmune diseases and solid neoplasms, can cause nephrotoxicity with glomerular and tubular dysfunction. The use of medicinal plants, due to their potent antioxidant actions, has been used for the prevention or treatment of cellular injuries induced by the imbalance between antioxidant and oxidant enzymes. For this reason, the aim of the experiment was to evaluate the potential protective effect of Echinodorus grandiflorus in preventing cyclophosphamide-induced nephrotoxicity. For this, the experiment was carried out with the use of 35 male Wistar rats, divided into six experimental groups, being administered cyclophosphamide at a dose of 150mg/kg in groups G2 to G6 and different doses of Echinodorus grandiflorus, with subsequent analysis of parameters blood and histology. The administration of cyclophosphamide at a dose of 150mg/kg of body weight, in a single dose, was able to induce acute nephrotoxicity in all rats. The crude extract of Echinodorus grandiflorus showed a potential renoprotective effect with the use of cyclophosphamide, at a dose of 300mg/kg of body mass, and it was possible to observe a reduction in the nephrotoxic effects of the chemotherapy, due to the reduction of tubular damage and the reduction of capsule spaces, clearly found altered in the group that received only cyclophosphamide, showing promising results for the use of this medicinal plant in the prevention of drug-induced nephrotoxicity. However, further studies of the renoprotective effects of the leather hat may elucidate the mechanisms involved in the action of the crude extract of the leather hat. The use of raw extract of medicinal plants becomes an adjuvant to treatments due to the low cost and ease of access of different populations to plants, provided that they are properly guided by qualified professionals.
Debido a las características anatómicas y fisiológicas de los riñones, la lesión renal aguda tiene su origen nefrotóxico por la elevada circulación local, que favorece la alta concentración de sustancias tóxicas y sus metabolitos en el tejido. La lesión renal aguda es una complicación frecuente en los ingresos hospitalarios y principalmente en las unidades de cuidados intensivos. La ciclofosfamida, un quimioterápico utilizado en el tratamiento de enfermedades autoinmunes y neoplasias sólidas, puede causar nefrotoxicidad con disfunción glomerular y tubular. El uso de plantas medicinales, debido a sus potentes acciones antioxidantes, se ha utilizado para la prevención o el tratamiento de lesiones celulares inducidas por el desequilibrio entre enzimas antioxidantes y oxidantes. Por este motivo, el objetivo del experimento era evaluar el posible efecto protector del Echinodorus grandiflorus en la prevención de la nefrotoxicidad inducida por la ciclofosfamida. Para ello, se realizó el experimento utilizando 35 ratas Wistar macho, divididas en seis grupos experimentales, administrándoseles ciclofosfamida a una dosis de 150mg/kg en los grupos G2 a G6 y diferentes dosis de Echinodorus grandiflorus, con posterior análisis de sangre y parámetros histológicos. La administración de ciclofosfamida a una dosis de 150mg/kg de masa corporal, en dosis única, fue capaz de inducir nefrotoxicidad aguda en todas las ratas. El extracto crudo de Echinodorus grandiflorus presentó un potencial efecto renoprotector al uso de ciclofosfamida, a una dosis de 300mg/kg de masa corporal, siendo posible observar una reducción de los efectos nefrotóxicos de la quimioterapia, por la reducción del daño tubular y por la disminución de los espacios capsulares, encontrándose claramente alterados en el grupo que recibió solamente ciclofosfamida, denotando resultados promisorios para el uso de esta planta medicinal en la prevención de la nefrotoxicidad inducida por el fármaco. Sin embargo, nuevos estudios sobre los efectos renoprotectores del sombrero de cuero podrían dilucidar los mecanismos implicados en la acción del extracto crudo de sombrero de cuero. El uso de extractos crudos de plantas medicinales se convierte en un coadyuvante de los tratamientos por su bajo coste y la facilidad de acceso de las diferentes poblaciones a las plantas desde que son guiadas adecuadamente por profesionales cualificados.
Subject(s)
Animals , Rats , Cyclophosphamide/analysis , Alismataceae/toxicity , Acute Kidney Injury/drug therapy , Plants, Medicinal/drug effects , Body Weight/drug effects , Pharmaceutical Preparations/analysis , Mesna/toxicity , Rats, WistarABSTRACT
This study evaluates the toxicological, genotoxic, mutagenic and apoptotic potential of an in vivo assay from Echinodorus macrophyllus extract (EEM). The acute toxicity test used 02 groups (n = 5) of female Wistar rats: negative control group (saline) and experimental group (2000 mg/kg b.w. EEM), both orally administered (gavage) at single doses and monitored for 14 days. To assess the genotoxic, mutagenic and apoptotic potential, 50 male Swiss mice were divided into 5 groups (n = 10): Group I: negative control (saline solution 0.1 ml/10 g b.w.); Group II: positive control (cyclophosphamide 100 mg/kg b.w.) intraperitoneally administered; groups III-V received EEM at 500, 1000 and 2000 mg/kg b.w., respectively. Groups I, III-V received oral administrations (gavage). The results showed that there was no acute lethality or any signs of acute toxicity, indicating that LD50 is greater than 2000 mg/kg b.w. The groups treated with EEM showed no genotoxic or mutagenic activity and did not induce apoptosis in the liver and kidney. Therefore, EEM showed no acute toxicity and at doses of 500, 1000 and 2000 mg/kg b.w. absence of genotoxicity, mutagenicity and no apoptotic events were observed.
Subject(s)
Alismataceae/toxicity , Apoptosis/drug effects , Ethanol/chemistry , Kidney/drug effects , Liver/drug effects , Plant Extracts/toxicity , Plant Leaves/toxicity , Solvents/chemistry , Toxicokinetics , Administration, Oral , Alismataceae/chemistry , Animals , Chromatography, High Pressure Liquid , Comet Assay , Female , Injections, Intraperitoneal , Kidney/pathology , Lethal Dose 50 , Liver/pathology , Male , Mice , Micronucleus Tests , Phytotherapy , Plant Extracts/administration & dosage , Plant Extracts/isolation & purification , Plant Leaves/chemistry , Plants, Medicinal , Rats, Wistar , Risk Assessment , Time Factors , Toxicity Tests, AcuteABSTRACT
Extracts of Echinodorus grandiflorus obtained from dried leaves by three different techniques were evaluated by bacterial lysogenic induction assay (Inductest) in relation to their genotoxic properties. Before being added to test cultures, extracts were sterilized either by steam sterilization or ultraviolet light. Only the extracts prepared by infusion and steam sterilized have shown genotoxic activity. The phytochemical analysis revealed the presence of the flavonoids isovitexin, isoorientin, swertisin and swertiajaponin, isolated from a genotoxic fraction. They were assayed separately and tested negative in the Inductest protocol. The development of browning color and sweet smell in extracts submitted to heat, prompted further chemical analysis in search for Maillard's reaction precursors. Several aminoacids and reducing sugars were cast in the extract. The presence of characteristic Maillard's melanoidins products was determined by spectrophotometry in the visible region and the inhibition of this reaction was observed when its characteristic inhibitor, sodium bisulfite, was added prior to heating. Remarkably, this is the first paper reporting on the appearance of such compounds in a phytomedicine preparation under a current phytopharmaceutical procedure. The genotoxic activity of such heat-prepared infusions imply in some risk of developing degenerative diseases for patients in long-term, uncontrolled use of such phytomedicines.
Subject(s)
Alismataceae/toxicity , DNA Damage/drug effects , DNA, Bacterial/drug effects , Plant Extracts/toxicity , Alismataceae/chemistry , Escherichia coli/drug effects , Escherichia coli/genetics , Mutagenicity Tests/methodsABSTRACT
To evaluate the possible toxicity of the aqueous extract of Echinodorus grandiflorus in pregnant rats, animals were distributed in groups treated with 250, 500 and 1,000 mg/kg/day, by gavage, and a control group received saline solution. The treatment was carried out for 15 consecutive days, remaining during mating and until the 14(th) day of gestation. On the 15(th )day, pregnant animals were euthanized by exsanguination under anesthesia. A blood sample was destined to the hematological and biochemical analysis. The ovaries, liver, kidneys, spleen, and adrenal glands were removed and weighed. Liver, kidneys and spleen were processed for histopathological analysis. The number mated, cohabitated and pregnant rats were counted as well as the corpora lutea, implants, resorptions, and live and dead fetuses. Fetus body weight and placenta were measured. Treatment with 1,000 mg of extract caused anemia, leukocytosis, and an increase in AST and in cholesterol. The liver of animals treated with the two higher doses exhibited discrete inflammatory reaction, located mainly at the stroma which supports the portal space; in the kidneys of animals of T-500 and T-1000 groups there was an expressive decrease in the capsular space, and focal areas of vasodilatation and congestion, as well as a discrete hyalinization, and in the spleen of T-1000 group the red pulp presented excessive pigmentation suggestive of hemosiderin. There were no alterations in reproductive parameters, in fetus external morphology or in placenta weight. In conclusion, the extract causes maternal toxicity, though it does not alter the reproductive performance.
