Anti-inflammatory and diuretic effects of the diterpene ent-dihydrotucumanoic acid.

Gymnosperma glutinosum (Spreng) Less (Asteraceae) is a shrub used in traditional medicine for the treatment of inflammatory and renal diseases. The ent-dihydrotucumanoic acid (DTA) is a diterpene obtained from G. glutinosum. This study evaluated the antioxidant, genotoxic, and diuretic properties of DTA, as well as its in vitro and in vivo anti-inflammatory actions. The antioxidant actions of DTA were assessed with the 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), ferric reducing antioxidant power (FRAP), and 2,2'-diphenyl-1-picrylhydrazyl (DPPH) assays, the genotoxic action was assessed with the comet assay, and the diuretic effects of DTA were assessed using metabolic cages. The anti-inflammatory actions were evaluated using primary murine peritoneal macrophages stimulated with LPS and the λ-carrageenan-induced hind paw edema test. DTA lacked antioxidant (IC50 > 25,000 µg/mL) activity in the ABTS, FRAP, and DPPH assays. DTA at 500-1,000 µg/mL showed moderate genotoxicity. In LPS-stimulated macrophages, DTA showed IC50 values of 74.85 µg/mL (TNF-α) and 58.12 µg/mL (NO), whereas the maximum inhibition of IL-6 (24%) and IL-1ß (36%) was recorded at 200 µg/mL. DTA induced in vivo anti-inflammatory effects with ED50 = 124.3 mg/kg. The in vitro anti-inflammatory activity of DTA seems to be associated with the decrease in the release of TNF-α and NO. DTA promoted the excretion of urine (ED50 = 86.9 mg/kg), Na+ (ED50 = 66.7 mg/kg), and K+ (ED50 = 8.6 mg/kg). The coadministration of DTA with L-NAME decreased the urinary excretion shown by DTA alone. Therefore, the diuretic activity is probably associated with the participation of nitric oxide synthase. In conclusion, DTA exerted anti-inflammatory and diuretic effects, but lacked antioxidant effects.

Uso inapropiado de diuréticos: Algunas características no tan conocidas / Diuretic misuse: Some not so well known characteristics

Entre las situaciones asociadas al uso inapropiado de diuréticos se encuentran los intentos por descencer rápidamente de peso, comunes en los desordenes de la alimentación, y los intentos por enmascarar el consumo de otras sustancias, en el caso de las competencias deportivas. El uso sin indicación ni supervisión médica de estos fármacos genera un desbalance electrolítico, que puede manifestarse con hiponatremia, hipocalemia, hipocalcemia e hipomagnesemia, hipercalemia, entre otras alteraciones. El objetivo de este trabajo fue investigar las caracteríscas del uso inapropiado de diuréticos a partir de la casuística del CENATOXA. Se realizó un estudio descriptivo restrospectivo sobre los análisis ingresados al CENATOXA con solicitud de investigación cualitativa de diuréticos en orina, entre los años 2002 y 2016. En dicho período ingresaron al CENATOXA 138 casos, de los cuales el 56 % resultó positivo para algún diurético. Del total de casos con resultado positivo, el 93,5 % fueron mujeres entre 25 y 55 años de edad y predominó la etiología intencional. Los diuréticos mayoritariamente encontrados fueron hidroclorotiazida y furosemida. El perfil de diuréticos hasta el año 2008 (hidroclorotiazida = 68% de los casos positivos) se diferenció del hallado entre 2009 y 2016 (furosemida + hidroclorotiazida = 60% de los casos positivos). Se observó recurrencia en el uso inapropiado en el 8% de los casos. El uso simultáneo de más de un diurético y la recurrencia son factores que pueden contribuir a la aparición de toxicidad. Estos resultados sugieren que el uso inapropiado de diuréticos es una situación que debería ser ob­servada más atentamente para establecer mejor su alcance y sus riesgos.

Among the situations associated with diuretics misuse are the attempts to lose weight fast, frequently observed in eating disorders, and the attempts to mask the consumption of other substances, in the case of sports competitions. The use of these drugs with no medical indication or supervision generates an electrolyte imbalance, leading to hyponatremia, hypokalemia, hypocalcemia and hypomagnesemia, hyperkalemia, among other alterations. The objective of this work was to investigate the characteristics of diuretics misuse from the CENATOXA database, where the qualitative investigation of diuretics in urine is per­formed. A descriptive retrospective study was conducted on the cases admitted to the CENATOXA with a request for qualitative diuretic investigation, between 2002 and 2016. During this period, 138 urine samples were received at the CENATOXA and 56% were positive for at least one diuretic. Of all cases with positive results, 93.5% were women between 25 and 55 years of age, and intentional etiology predominated. The most detected diuretics were hydrochlorothiazide and furosemide. The diuretic misuse pattern detected up to 2008 (hydrochlorothiazide = 68% of positive cases) differed from that detected between 2009 and 2016 (furosemide + hydrochlorothiazide = 60% of positive cases). Recurrence in misuse was observed in 8% of the cases. The simul­taneous misuse of more than one diuretic and the recurrence are factors that can contribute to the onset of toxicity. These results suggest that diuretic misuse is a situation that should be observed more closely to better assess its consequences and its risks.

Ethnopharmacological approaches to kidney disease-prospecting an indigenous species from Brazilian Pantanal.

ETHNOPHARMACOLOGICAL RELEVANCE: Although Luehea divaricata Mart. (Malvaceae) is popularly used by the population of the Brazilian Pantanal for the treatment of different types of kidney diseases, no study has been carried out to prove this ethnobotanical indication. AIM: To investigate the possible cardiorenal effects of an herbal preparation obtained from L. divaricata leaves. MATERIALS AND METHODS: First, to provide quality control standards, a detailed morphological and microchemical characterization of L. divaricata leaves was performed. Then, the purified aqueous extract was obtained from the leaves of this species (ESLD) and a thorough phytochemical characterization was performed. Subsequently, acute oral toxicity test was performed after single administration of different doses (5, 50, 300, 2000mg/kg) in male and female Wistar rats. Finally, the diuretic, hypotensive and antioxidant properties of ESLD (30, 100, 300mg/kg) were evaluated after acute and prolonged treatment and the role of angiotensin converting enzyme, aldosterone, vasopressin, and nitric oxide in these effects was investigated. RESULTS: Analyses performed by liquid chromatography-mass spectrometry showed that the main secondary metabolites present in ESLD were flavonol O-glycosides and flavone C-glycosides. Acute and prolonged treatment with ESLD was able to expressively increase urinary volume and electrolyte excretion. Mean blood pressure and systolic blood pressure were also significantly reduced after acute treatment. Moreover, treatment with ESLD was able to reduce thiobarbituric acid reactive species and increase serum nitrate levels. CONCLUSION: The data obtained showed that ESLD has an important diuretic and hypotensive effect, which is probably dependent on the reduction of oxidative stress and increased bioavailability of nitric oxide.

[Acute diuretic effect of ethanolic and aqueous extracts of Ceratopteris pteridoides (Hook) in normal rats]. / Efecto diurético agudo de los extractos etanólico y acuoso de Ceratopteris pteridoides (Hook) en ratas normales.

INTRODUCTION: Ceratopteris pteridoides is a semiaquatic fern of the Parkeriacea family, widely used in the Colombian folk medicine as a diuretic and cholelithiasic, of which there are no scientific reports that validate its popular use. OBJECTIVE: To evaluate the acute and short-term repeated-dose diuretic effect of the ethanolic and aqueous extracts of C. pteridoides in an in vivo model. MATERIALS AND METHODS: The total ethanolic extract was obtained by maceration of the whole plant of C. pteridoides with ethanol and the aqueous extract by decoction at 60°C for 15 minutes. Both extracts were evaluated in preliminary phytochemical analysis and histological studies after the administration of the extracts for 8 consecutive days (1000 mg/Kg). The diuretic effect was evaluated using Wistar rats treated with the extracts (500 mg/Kg), using an acute and a short-term repeated-dose model, and quantifying water elimination, sodium and potassium excretion by atomic absorption spectrophotometry, and chloride excretion by mercurimetric titration. RESULTS: In the acute model both extracts showed significant diuretic, natriuretic, and kaliuretic effect compared to the control group. Whereas, a short-term repeated-dose administration showed a diuretic effect without elimination of electrolytes. The histopathologic study did not suggest a toxic effect in liver or kidney. CONCLUSION: The results represent evidence of the diuretic activity of C. pteridoides and give support the popular use given to this plant in the north coast of Colombia. Further studies are required to isolate and identify the compounds responsible for the activity and the mechanism of action involved.

Efecto diurético agudo de los extractos etanólico y acuoso de Ceratopteris pteridoides (Hook) en ratas normales / Acute diuretic effect of ethanolic and aqueous extracts of Ceratopteris pteridoides (Hook) in normal rats

Introducción. Ceratopteris pteridoides es un helecho semiacuático de la familia Parkeriacea, ampliamente utilizado en la medicina popular colombiana como diurético y colelitiásico, sobre el cual no existen reportes científicos que avalen su uso popular como diurético. Objetivo. Evaluar el efecto diurético agudo en dosis única y dosis repetidas a corto plazo, de los extractos etanólico y acuoso de C. pteridoides en un modelo in vivo . Materiales y métodos. El extracto etanólico total fue obtenido por maceración de la planta entera de C. pteridoides con etanol y el extracto acuoso fue obtenido por decocción a 60 °C por 15 minutos. Ambos extractos se sometieron a análisis fitoquímico preliminar y estudio histológico posterior a la administración de los extractos durante ocho días consecutivos (1.000 mg/kg). El efecto diurético se evaluó en ratas Wistar, tratadas con los extractos (500 mg/kg), en forma aguda y en dosis repetidas a corto plazo, cuantificando la eliminación de agua y la excreción renal de sodio y potasio por espectrofotometría de absorción atómica y, de cloruros, por titulación mercurimétrica. Resultados. En el modelo agudo, ambos extractos mostraron un significativo efecto diurético y de excreción renal de sodio y potasio en comparación con el control, mientras que con la administración en dosis repetidas a corto plazo mostraron efecto diurético sin eliminación de electrolitos. El estudio histopatológico no sugirió efectos tóxicos hepáticos o renales. Conclusión. Los resultados demuestran la actividad diurética de C. pteridoides y sustentan el uso popular dado a esta planta como diurético en la costa norte colombiana. Se requieren estudios posteriores que permitan aislar e identificar los compuestos responsables de la actividad y los mecanismos de acción involucrados.

Introduction. Ceratopteris pteridoides is a semiaquatic fern of the Parkeriacea family, widely used in the Colombian folk medicine as a diuretic and cholelithiasic, of which there are no scientific reports that validate its popular use. Objective. To evaluate the acute and short-term repeated-dose diuretic effect of the ethanolic and aqueous extracts of C. pteridoides in an in vivo model. Materials and methods. The total ethanolic extract was obtained by maceration of the whole plant of C. pteridoides with ethanol and the aqueous extract by decoction at 60°C for 15 minutes. Both extracts were evaluated in preliminary phytochemical analysis and histological studies after the administration of the extracts for 8 consecutive days (1000 mg/Kg). The diuretic effect was evaluated using Wistar rats treated with the extracts (500 mg/Kg), using an acute and a short-term repeated-dose model, and quantifying water elimination, sodium and potassium excretion by atomic absorption spectrophotometry, and chloride excretion by mercurimetric titration. Results. In the acute model both extracts showed significant diuretic, natriuretic, and kaliuretic effect compared to the control group. Whereas, a short-term repeated-dose administration showed a diuretic effect without elimination of electrolytes. The histopathologic study did not suggest a toxic effect in liver or kidney. Conclusion. The results represent evidence of the diuretic activity of C. pteridoides and give support the popular use given to this plant in the north coast of Colombia. Further studies are required to isolate and identify the compounds responsible for the activity and the mechanism of action involved.

Diuretic activity and acute oral toxicity of Palicourea coriacea (Cham.) K Schum.

AIM OF THE STUDY: Palicourea coriacea (Cham.) K Schum, is an endemic plant used in the Midwestern Region of Brazil, popularly known as "douradinha do campo" and "congonha do campo". This plant has been used in traditional medicine for several ailments, especially to treat kidney diseases. Since no formal studies on the biological activities and medicinal properties of the ethanolic extract of Palicourea coriacea (PCEE) have been carried out previously, the present study represents the first research into the efficacy of this plant as a diuretic agent employing laboratory rats as test animals. MATERIALS AND METHODS: For diuretic activity evaluation we assayed three doses of PCEE (20, 40 and 80mg/kg) and measurement of the urinary volume and electrolytes (Na(+), K(+)) concentration were taken. The acute oral toxicity of PCEE was investigated according to OECD Guideline 423. RESULTS: The oral administration of a single dose of PCEE significantly increased the urinary volume in 24h. Additionally, the treatment with PCEE increased, in a dose-dependent manner, the excretion of both, Na(+) and K(+). No sign of toxicity was observed in the animals. CONCLUSIONS: The present study confirmed the ethnopharmacological use of Palicourea coriacea as a diuretic agent in the experimental condition tested here. Additionally, this work supports the importance of the preservation of local knowledge as well as the conservation of Brazilian biodiversity.

Acute toxicity and diuretic studies of the roots of Asparagus racemosus Willd in rats.

OBJECTIVE: Asparagus racemosus Willd has been used as diuretic in Ayurveda but has not been validated by a suitable experimental model. Hence the present study was undertaken. MATERIALS AND METHODS: The study was carried out with an aqueous extract of the roots of Asparagus racemosus utilizing three doses viz 800 mg/kg, 1600 mg/kg and 3200 mg/kg for its diuretic activity in comparison with standard drug (furosemide) and control (normal saline) rats after doing acute toxicity study. RESULTS: Acute toxicity study showed no fatality even with the highest dose and the diuretic study revealed significant diuretic activity (p < 0.05) in the dose of 3200 mg/kg. CONCLUSION: Asparagus racemosus showed diuretic activity at a 3200 mg/kg dose without acute toxicity.

Acute toxicity and diuretic studies of the roots of Asparagus racemosus willd in rats / Toxicidad aguda y estudios diuréticos del espárrago racemoso willd en ratas

OBJECTIVE: Asparagusracemosus Willd has been used as diuretic in Ayurveda but has not been validated by a suitable experimental model. Hence the present study was undertaken. MATERIALS AND METHODS: The study was carried out with an aqueous extract of the roots of Asparagus racemosus utilizing three doses viz 800 mg/kg, 1600 mg/kg and 3200 mg/kg for its diuretic activity in comparison with standard drug (furosemide) and control (normal saline) rats after doing acute toxicity study. RESULTS: Acute toxicity study showed no fatality even with the highest dose and the diuretic study revealed significant diuretic activity (p < 0.05) in the dose of 3200 mg/kg. CONCLUSION: Asparagus racemosus showed diuretic activity at a 3200 mg/kg dose without acute toxicity.

OBJETIVO: El espárrago racemoso Willd ha sido usado como diurético en ayurveda pero no ha sido validado mediante un modelo experimental conveniente. De ahí la razón para emprender el presente estudio. MATERIALES Y MÉTODOS: El estudio fue realizado con extracto acuoso de raíces de espárrago racemoso, utilizando tres dosis, a saber, 800 mg/kg, 1600 mg/kg y 3200 mg/kg para analizar su actividad diurética, comparándolo con el medicamento estándar (furosemida), y ratas de control (solución salina normal) después de hacer un estudio de toxicidad aguda. RESULTADOS: El estudio de toxicidad aguda no mostró fatalidad, incluso con la dosis más alta, y el estudio del diurético reveló una actividad diurética significativa (p < 0.05) con la dosis de 3200 mg/kg. CONCLUSIÓN: El espárrago racemoso mostró actividad diurética en una dosis de 3200 mg/kg sin toxicidad aguda.

Hepatocytes isolated from preneoplastic rat livers are resistant to ethacrynic acid cytotoxicity.

Glutathione S-transferases (GSTs) are involved in the detoxification of xenobiotics, such as several cytostatic drugs, through conjugation with glutathione (GSH). Pi class GST (GST P) liver expression is associated with preneoplastic and neoplastic development and contributes with the drug-resistance phenotype. Ethacrynic acid (EA) is an inhibitor of rat and human GSTs. In addition, causes lipid peroxidation in isolated rat hepatocytes. Therefore, we decided to evaluate the role of the GST/GSH system in isolated hepatocytes from preneoplastic rat livers (IP) in the presence of EA and determine the cytotoxicity of the drug. Our results showed a resistance to the toxic effects of EA since viability and cellular integrity values were significantly higher than control. Initial levels of thiobarbituric acid reactive substances (TBARS) in IP hepatocytes were significantly higher than control and the presence of EA did not change TBARS levels. A diminution in intracellular total GSH was observed by treating with EA isolated hepatocytes from both groups. However, the initial total GSH levels were higher in IP hepatocytes than in control. Immunoblotting analysis showed the presence of GST P in IP animals only. Although alpha and mu class isoenzymes levels were decreased in IP hepatocytes, total GST activity was 1.5-fold higher than in control. In addition, multidrug-resistance protein 2 (Mrp2) showed fivefold decreased levels in IP hepatocytes. In conclusion, increased total GSH, decreased Mrp2 levels and the presence of GST P could be critical factors involved in the resistance of IP hepatocytes to the toxicity of EA.

Cardiovascular effects of the South American medicinal plant Cecropia pachystachya (ambay) on rats.

Cecropia pachystachya is used in South America for relieving cough and asthma. In Argentina it is known as "ambay" and grows in the neotropical forests (Ntr C.p.) and in temperate hilly regions (Tp C.p.). To evaluate their cardiovascular profile, the effect of extracts obtained from plants growing in the neotropical region as well as in temperate areas were compared by i.v. administration in normotensive rats. The following parameters were measured: blood pressure (BP) and heart rate (HR). The hypotensive effect was stronger for Ntr C.p., which aqueous extract decreased BP at doses between 90 and 300 mg lyophilised/kg until 46.2 +/- 12% of basal. The extract of Tp C.p. reduced BP to 86.1 +/- 11% of basal (p < 0.05 respect to Ntr C.p.) at 180 mg/kg, but increased HR at 90 and 180 mg/kg (until 133.6 +/- 10.8% of basal, p < 0.05) and produced death by respiratory paralysis at 320 mg/kg (about 3g dry leaves/kg). The hypotensive effects, but not the chronotropic ones, were attenuated by pretreatment with reserpine (5 mg/kg). The plant extracts had not diuretic activity by oral administration in conscious rats, nor produced vasodilation of perfused hindquarters arterial bed precontracted with high-[K] or 100 microM phenylephrine. The results suggest that neotropical ambay is more hypotensive than the one from the temperate hilly region. When it reaches plasma, it could produce hypotension (by central blockade of sympathic innervation of vessels) and tachycardia (by central cholinergic inhibition of heart), although it happens at doses higher than the oral ethnotherapeutic (about 340 mg dried leaves/kg).

Study of the photochemical and in vitro phototoxicity of chlortalidone [2-chloro-5-(1-hydroxy-3-oxo-1-isoindolinyl)benzene sulfonamide].

The photodegradation process of the phototoxic diuretic drug chlorthalidone was studied. The products of its photolysis under UV-B were isolated and identified. Chlorthalidone was found to be active when examined by photohemolysis on human erythrocytes, but not in the presence of the isolated photoproducts. Inhibition of the photohemolysis process induced by chlorthalidone on addition of reduced glutathione (GSH) or ascorbic acid suggests the involvement of radicals species. The inhibition with 1,4-diazabycyclo [2.2.2] octane (DABCO), sodium azide (NaN3) sowie 2,5-dimethylfuran proof the participation of singlet oxygen (1O2) in this process.

Photodegradation and phototoxicity studies of furosemide. Involvement of singlet oxygen in the photoinduced hemolysis and lipid peroxidation.

The phototoxic diuretic drug furosemide (1), a 5-(aminosulfonyl)-4-chloro-2-[(2-furanylmethyl)-amino] benzoic acid is photolabile under aerobic and anaerobic conditions. Irradiation of a methanol solution of 1 under oxygen produces photoproducts 2, 3, 4 and singlet oxygen, while under argon the photoproducts 2 and 4 were isolated. A peroxidic unstable photoproduct was detected during the photolysis under oxygen atmosphere. The formation of singlet oxygen by photolysis of 1 was evidenced by trapping with 2,5-dimethylfuran (GC-mass), furfuryl alcohol and 1,3-cyclohexadiene-1,4-diethanoate (HPLC) as 1O2 scavengers and by the histidine test. Furosemide was screened in vitro at different concentrations for UV-Vis-induced phototoxic effects in a photohemolysis test, in the presence and absence of different radical scavengers, singlet oxygen and hydroxyl radical quenchers. However, furosemide photosensitized the peroxidation of linoleic acid, as monitored by the UV-detection of dienic hydroperoxides and it also photosensitized the oxidation of histidine. The photodegradation was catalyzed in the presence of human serum albumin. Studies on peripheral blood mononuclear and polymorphonuclear cells (lymphocytes and neutrophils) demonstrated no phototoxicity on these cell lines.

Efecto diuretico y toxicidad aguda del Ortosiphon aristatus Blume (Te de rinon) / Diuretic effect and toxicity of Ortosiphon aristatus Blume (te de rinon)

Se realizo un estudio experimental en ratas con el objetivo de evaluar posible efecto diuretico y toxicidad aguda del Ortosiphon aristatus Blume (te de rinon). Para la accion diuretica se probaron tres niveles de dosis de la decoccion (20 porciento p/v), ademas se calcularon la DE 50 y dos de extracto fluido equivalentes a las dosis de decoccion. Los resultados fueron comparados con los obtenidos para la furosemida en dosis de 5, 10 y 20 mg/kg. La excrecion urinaria se midio por hora hasta la sexta hora, se le determinaron a este volumen final las concentraciones de sodio y potasio; tambien se analizaron estos electrolitos en el plasma sanguineo. Se comprobo la actividad diuretica de la de-coccion de Ortosiphon aristatus, efecto dosis dependiente acompanada de una natriuresis y kaluresis significativas, la DE 50 correspondio a 200 mg/kg. El extracto fluido no tuvo un comportamiento similar, debido fundamentalmente al vehiculo hidroalcoholico empleado en su prepararcion. El extracto fluido de Ortosiphon aristatus no mostro toxicidad en la dosis de 2 000 mg/kg

Pharmacological and toxicological evaluation of Alpinia speciosa.

Alpinia speciosa Schum or A. nutans is a plant of the Zingiberaceae family, known popularly as "colony" (colônia) and used as a diuretic and to control hypertension. We have determined the concentration of Na+ and K+ found in the alcoholic extract and in the tea concoction. They contained 51.0 mEq Na+, and 132 mEq K+ in the extract, and 0.0 mEq of Na+ and 26 mEq K+ in the tea. Phytochemical analysis of the leaves demonstrated the presence of catecquic tanins, phenols and alkaloids, and also some essential oils. When injected intra-peritoneally the hydroalcoholic extract, in a dose range of 100 to 1400 mg/kg, (or 2500-18000 mg/kg orally) produced in mice: writhing, psychomotor excitation, hypokinesis and pruritus. The LD50 by ip was 0.760 +/- 0.126 g/kg and 10.0 +/- 2.5 g/kg by oral administration for the hydroalcoholic extract. Subacute toxicity made by injecting daily for 30 days the LD10 in rats caused an increase in transaminases and lactate dehydrogenase, whereas other parameters such as blood glucose, urea and creatinine were normal. A histopathological analysis of liver, spleen, gut, lung and heart showed no alterations. The drug also produced a prolongation of the sleeping time. The hydroalcoholic extract induced in the rat and in the dog a dose-dependent fall in blood pressure in doses of 10 to 30 mg/kg. In isolated atria the extract induced a reduction of the frequency and in the inotropic responses. Neither the extract nor the tea had an effect on the diuresis of the rat.

Pharmacological and toxicological evaluation of Alpinia speciosa

Alpinia speciosa Schum or A. nutans is a plant of the Zingiberanceae family, Known popularly as "colony" (colônia) and used as a diuretic and to control hypertensión. We have determinated the concentration of Na+ and K+ found in the alcoholic extract and in the tea concoction. They contained 51.0mEq Na+, and 132 mEq K+ in the extract, and 0,0 mEq of Na+ and 26 mEq K+ in the tea. Phytochemical analysis of the leaves demonstrated the presence of catecquic tanins, phenols and alkaloids, and also some essential oils. When injected intra-peritoneally the hydroalcoholic extract, in range of 100 a 1400 mg/Kg, (or 2500-18000 mg/Kg orally) produced in mice: writhing, psychomorot excitation, hypokinesis and pruritus. The LD50 by ip was 0.760 + or - 0.126 g/Kg and 10.0 + or - 2.5 g/Kg by oral administration for the hydroalcoholic extract. Subacute toxicity made injecting daily for 30 days the LD10 in rats caused an increase in transaminases and lactate dehydrogenase, whereas other parameters such as nlood glucose, urea and creatinine were normal. A histopathological analysis of liver, spleen, gut, lung and heart showed no alterations. The drug also produced a prolongation of the sleeping time. The hydroalcoholic extract induced int he rat and in the dog a dose-dependent fall in blood pressure in doses of 10 to 30 mg/Kg. In isolated atria the extract induced a reduction of the frequnecy and in the inotropic responses. Neither the extract nor the tea had an effect on the diuresis of the rat.

Effect of xipamide and furosemide on guinea pig cochlear recorded potentials.

The effects of furosemide and xipamide on guinea pig cochlear potentials were studied under acute conditions. Auditory nerve action potentials (AP) and cochlear microphonics (CM) were depressed by both diuretics in a dose-related manner. Furosemide was more effective on AP than on CM. In contrast, the xipamide-induced reductions of AP and CM were similar. Our results suggest that the depressive effects of furosemide or xipamide may be related to a direct action on cochlear mechanisms.