RESUMEN
The study of pharmacological interactions between herbal remedies and conventional drugs is important because consuming traditional herbal remedies as supplements or alternative medicine is fairly common and their concomitant administration with prescribed drugs could either have a favorable or unfavorable effect. Therefore, this work aims to determine the pharmacological interactions of a turmeric acetone extract (TAE) and its main metabolite (curcumin) with common anti-ulcer drugs (ranitidine and bismuth subsalicylate), using an ethanol-induced ulcer model in Wistar rats. The analysis of the interactions was carried out via the Combination Index-Isobologram Equation method. The combination index (CI) calculated at 0.5 of the affected fraction (fa) indicated that the TAE or curcumin in combination with ranitidine had a subadditive interaction. The results suggest that this antagonistic mechanism is associated to the mucoadhesion of curcumin and the TAE, determined by rheological measurements. Contrastingly, both the TAE and curcumin combined with bismuth subsalicylate had an additive relationship, which means that there is no pharmacological interaction. This agrees with the normalized isobolograms obtained for each combination. The results of this study suggest that mucoadhesion of curcumin and the TAE could interfere in the effectiveness of ranitidine, and even other drugs.
Asunto(s)
Antiulcerosos/uso terapéutico , Bismuto/uso terapéutico , Curcumina/farmacología , Etanol/efectos adversos , Compuestos Organometálicos/uso terapéutico , Extractos Vegetales/farmacología , Ranitidina/uso terapéutico , Salicilatos/uso terapéutico , Úlcera Gástrica/prevención & control , Animales , Antiulcerosos/antagonistas & inhibidores , Curcuma , Modelos Animales de Enfermedad , Interacciones Farmacológicas , Mucosa Gástrica/efectos de los fármacos , Interacciones de Hierba-Droga , Masculino , Compuestos Organometálicos/antagonistas & inhibidores , Ranitidina/antagonistas & inhibidores , Ratas , Ratas Wistar , Salicilatos/antagonistas & inhibidores , Úlcera Gástrica/inducido químicamenteRESUMEN
BACKGROUND: Lead without nutritional value is a widely studied occupational and environmental toxicant. Leads' toxic effects on female reproduction are decreased fertility, inability to sustain pregnancy and reduced pregnancy. OBJECTIVE: This study aimed at examining the effect of oral administration of lead acetate (1.5 mg/kg) on the histology of female albino Wistar rats' ovary and Uterus and the extracts' protective role against toxicity. METHODS: The experiment took 28 days involving 25 female Wistar rats divided into 5 groups A, B, C, D and E. A is an untreated group that received normal saline, D lead acetate group that received lead acetate solution, E received aqueous extract, B and C low and high dose of aqueous extract respectively and lead acetate solution. RESULTS: The positive control group showed a significant increase in SOD at P ≤ 0.01 compared to the negative control. Group E showed significant decrease ovarian SOD. The organs weights were significantly reduced in group D. The changes seen in the organs include oedema, necrosis, optical empty spaces, denudations and fatty changes. Administrating the extract protected the organs against the lead acetate. These alterations are shown to cause infertility in female rats. CONCLUSION: The results suggested that the extract has protective role against lead reproductive toxicity.
Asunto(s)
Ficus/química , Compuestos Organometálicos/antagonistas & inhibidores , Compuestos Organometálicos/toxicidad , Ovario/diagnóstico por imagen , Extractos Vegetales/farmacología , Útero/efectos de los fármacos , Administración Oral , Animales , Relación Dosis-Respuesta a Droga , Femenino , Compuestos Organometálicos/administración & dosificación , Extractos Vegetales/administración & dosificación , Extractos Vegetales/aislamiento & purificación , Embarazo , Ratas , Ratas WistarRESUMEN
Lead (Pb)-induced reproductive toxicity is a well-characterized adverse effect associated with this heavy metal. It has been found that Pb exposure is associated with altered spermatogenesis, increased testicular degeneration, and pathological sperm alterations. On the other hand, it has been reported that Pb-induced reproductive toxicity is associated with increased reactive oxygen species (ROS) formation and diminished antioxidant capacity in the reproductive system. Hence, administration of antioxidants as protective agents might be of value against Pb-induced reproductive toxicity. This study was designed to investigate whether carnosine (CAR) and histidine (HIS) supplementation would mitigate the Pb-induced reproductive toxicity in male rats. Animals received Pb (20 mg/kg/day, oral, 14 consecutive days) alone or in combination with CAR (250 and 500 mg/kg/day, oral, 14 consecutive days) or HIS (250 and 500 mg/kg/day, oral, 14 consecutive days). Pb toxicity was evident in the reproductive system by a significant increase in tissue markers of oxidative stress along with severe histopathological changes, seminal tubule damage, tubular desquamation, low spermatogenesis index, poor sperm parameters, and impaired sperm mitochondrial function. It was found that CAR and HIS supplementation blunted the Pb-induced oxidative stress and mitochondrial dysfunction in the rat reproductive system. Thereby, antioxidative and mitochondria-protective properties serve as primary mechanisms for CAR and HIS against Pb-induced reproductive toxicity.
Asunto(s)
Carnosina/farmacología , Histidina/farmacología , Mitocondrias/efectos de los fármacos , Compuestos Organometálicos/antagonistas & inhibidores , Sustancias Protectoras/farmacología , Espermatozoides/efectos de los fármacos , Animales , Antioxidantes/metabolismo , Carnosina/administración & dosificación , Suplementos Dietéticos , Histidina/administración & dosificación , Masculino , Mitocondrias/metabolismo , Compuestos Organometálicos/toxicidad , Sustancias Protectoras/administración & dosificación , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Lead acetate (Led) and mercury chloride (Mer) represent important ecological and public health concerns due to their hazardous toxicities. Naturally found products play a vital role in chemopreventive agent innovation. The current study aimed to assess the modifying effect of garlic (Gar) and/or vitamin E (Vit E) against the half-maximal inhibitory concentration (IC50) Led and/or Mer-induced cytotoxic, genotoxic and apoptotic effects. METHODS: Human lung cells (WI-38) were pretreated with Gar and/or Vit E for 24h and then treated with Led and/or Mer either alone or with their combination for 24h. Cytotoxicity of Led and Mer and the viability of Gar and Vit E were assessed using MTT assay. The alkaline comet assay was used to assess DNA damage, whereas QRT-PCR was performed to evaluate p53, Bax, and Bcl2 mRNA-expression. RESULTS: The results of this study showed that IC50 of Led was (732.72µg/mL) and for Mer was (885.83µg/mL), while cell viability effective dose for Gar was (300µg/mL) and for Vit E was (26,800µg/mL). Treating cells with the IC50-concentration of Led or Mer or their combination using half IC50 of both of them induced severe DNA-damage. Bax-expression was increased, while p53 and Bcl2-expressions were decreased. Pretreatment of cells with Gar and/or Vit E ameliorated the previous alternations. CONCLUSIONS: Led and Mer can induce oxidative stress and change the expressions of apoptosis-related proteins in WI-38 cells. Gar and Vit E may be promising protective candidate agent against the toxic effect of heavy metals.
Asunto(s)
Apoptosis/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Ajo/química , Cloruro de Mercurio/antagonistas & inhibidores , Compuestos Organometálicos/antagonistas & inhibidores , Sustancias Protectoras/farmacología , Vitamina E/farmacología , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Interacciones de Hierba-Droga , Humanos , Cloruro de Mercurio/toxicidad , Compuestos Organometálicos/toxicidad , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Proteína p53 Supresora de Tumor/biosíntesis , Proteína X Asociada a bcl-2/biosíntesisRESUMEN
Flavonoids are agents with strong antioxidant properties and ameliorate many diseases associated with oxidative stress. Leaves of Casimiroa sapota were investigated for components and antioxidant/anti-inflammatory activities against lead acetate ((AcO)2 Pb) induced hepatotoxicity in rats. Three groups of male albino rats were administrated orally with vehicle or C. sapota (100 and 200 mg/kg b.w/day) for 28 days; other group was injected with sub-acute dose (100 mg/kg b.w/day) of (AcO)2 Pb. Three protective groups were injected with (AcO)2 Pb (100 mg/kg b.w/day) for 7 days at day 22 after treatment with either C. sapota (100 or 200 mg/kg b.w/day) or silymarin (SILY) for 28 days. We isolated and identified, from C. sapota, a new compound for the 1st time in nature; 5,6,2',3'-tetramethoxyflavone in addition to the rare compound 5,6,3'-trimethoxyflavone (second report of isolation from nature) and the known compound 5,6,2',3',4'-pentamethoxyflavone. There is an improvement in all hemato-biochemical parameters, antioxidant defense system and anti-inflammatory cytokines of protective groups, which received C. sapota in dose dependent manner. The percentage of changes in all parameters measured in (AcO)2 Pb groups that received vehicle, CS100, CS200 or SILY were 109.2, 37.3, 12.5%, and 1.2% compared with the healthy control group. The C. sapota groups confer a better antioxidant activity by preventing oxidative stress and inflammation in (AcO)2 Pb treated rats. The compounds isolated are responsible at least in part for the observed protective effects.
Asunto(s)
Casimiroa/química , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Flavonas/farmacología , Compuestos Organometálicos/antagonistas & inhibidores , Extractos Vegetales/farmacología , Hojas de la Planta/química , Animales , Relación Dosis-Respuesta a Droga , Flavonas/química , Flavonas/aislamiento & purificación , Masculino , Estructura Molecular , Compuestos Organometálicos/toxicidad , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Ratas , Relación Estructura-ActividadRESUMEN
In this study, the effect of geraniol (50 mg/kg for 30 d), a natural antioxidant and repellent/antifeedant monoterpene, in a rat model of lead acetate-induced (500 ppm for 30 d) liver damage was evaluated. Hepatic malondialdehyde increased in the lead acetate group. Reduced glutathione unchanged, but glutathione S-transferase, glutathione reductase, as well as carboxylesterase activities decreased in geraniol, lead acetate and geraniol + lead acetate groups. 8-OhDG immunoreactivity, mononuclear cell infiltrations and hepatic lead concentration were lower in the geraniol + lead acetate group than the lead acetate group. Serum aspartate aminotransferase and alanine aminotransferase activities increased in the Pb acetate group. In conclusion, lead acetate causes oxidative and toxic damage in the liver and this effect can reduce with geraniol treatment. However, we first observed that lead acetate, as well as geraniol, can affect liver carboxylesterase activity.
Asunto(s)
Carboxilesterasa/antagonistas & inhibidores , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Repelentes de Insectos/uso terapéutico , Intoxicación por Plomo/prevención & control , Hígado/efectos de los fármacos , Sustancias Protectoras/uso terapéutico , Terpenos/uso terapéutico , Monoterpenos Acíclicos , Animales , Antioxidantes/efectos adversos , Antioxidantes/uso terapéutico , Biomarcadores/sangre , Biomarcadores/metabolismo , Carboxilesterasa/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/enzimología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Enfermedad Hepática Inducida por Sustancias y Drogas/fisiopatología , Glutatión/química , Glutatión/metabolismo , Glutatión Reductasa/metabolismo , Glutatión Transferasa/metabolismo , Repelentes de Insectos/efectos adversos , Intoxicación por Plomo/metabolismo , Intoxicación por Plomo/patología , Intoxicación por Plomo/fisiopatología , Peroxidación de Lípido/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Hígado/fisiopatología , Masculino , Compuestos Organometálicos/antagonistas & inhibidores , Compuestos Organometálicos/toxicidad , Oxidación-Reducción , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras/efectos adversos , Distribución Aleatoria , Ratas Wistar , Terpenos/efectos adversosRESUMEN
Lead, one of the most harmful heavy metals, can cause various hazardous effects on living organisms. This study was undertaken to evaluate the antagonistic and protective effects of two economically important laver species, Pyropia yezoensis and P. haitanensis, against subchronic lead poisoning in rats by a 30-day feeding test. Sixty-four healthy Wistar rats were randomly divided into eight groups with eight rats (4â + 4â) per group, among which, one group was served as the control, the others were respectively treated with lead acetate (5 mg/kg b w), and a combination of lead acetate and P. yezoensis or P. haitanensis at different dosages. Weight gain of rats was observed and recorded. Changes in antioxidant indexes, and liver and renal function markers were determined to evaluate the antagonistic effect. Lead content in rats was determined to investigate lead excretion effect of laver. The results showed that exposure to lead caused lead accumulation in kidney and liver, thus leading to significant oxidative damage and impaired liver and renal function compared to the control group. The co-treatment of laver slightly increased body weight compared to the lead-treated group. The co-administration of laver restored liver and renal function of rats by preventing the increment in the activities of alanine transaminase (ALT), alkaline phosphatase (ALP), and aspartate transaminase (AST), and the levels of blood urea nitrogen (BUN) and creatinine (Cr). The increasing of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities, and lowering of the enhanced malondialdehyde (MDA) contents of rats were observed in the laver co-treated groups, which indicated that laver enhanced the antioxidative capacity of rats. The laver also enhanced lead content in feces and reduced it in liver and kidney. The results indicated that P. yezoensis and P. haitanensis could maintain or promote the normal physiological and biochemical function of lead-induced subchronic poisoning of rats, probably owing to their enhancements of antioxidant capacity and lead excretion.
Asunto(s)
Antioxidantes/farmacología , Intoxicación por Plomo/tratamiento farmacológico , Compuestos Organometálicos/antagonistas & inhibidores , Extractos Vegetales/farmacología , Rhodophyta/química , Animales , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Riñón/efectos de los fármacos , Riñón/metabolismo , Intoxicación por Plomo/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Compuestos Organometálicos/administración & dosificación , Compuestos Organometálicos/toxicidad , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Ratas , Ratas Wistar , Distribución TisularRESUMEN
The aim of this study was to investigate the beneficial effects of zinc (Zn) in preventing lead (Pb)-induced reproductive toxicity in Wistar rats. The rats were divided into four groups, namely, control group, Pb group, Zn group, and Pb + Zn group. Animals were exposed to Pb (819 mg of Pb/L) or Zn (71 mg of Zn/L) or both through drinking water for 65 days. Rats exposed to Pb showed decreased weights of testes and accessory sex organs. Significant decrease in the testicular daily sperm production, epididymal sperm count, motility, viability, and number of hypoosmotic tail coiled sperm was observed in Pb-exposed rats. Testicular 3ß- and 17ß-hydroxysteroid dehydrogenase activity levels and circulatory testosterone levels were also decreased significantly in Pb-exposed rats. A significant increase in the lipid peroxidation products with a significant decrease in the activities of catalase and superoxide dismutase were observed in the testes and epididymis of Pb-exposed rats. Moreover, the testicular architecture showed lumens devoid of sperm in Pb-exposed rats. Supplementation of Zn mitigated Pb-induced oxidative stress and restored the spermatogenesis and steroidogenesis in Pb-exposed rats. In conclusion, cotreatment of Zn is effective for recovering suppressed spermatogenesis, steroidogenesis, elevated oxidative status, and histological damage in the testis of rats treated with Pb.
Asunto(s)
Suplementos Dietéticos , Epidídimo/efectos de los fármacos , Infertilidad Masculina/prevención & control , Intoxicación por Plomo/prevención & control , Estrés Oxidativo/efectos de los fármacos , Testículo/efectos de los fármacos , Zinc/uso terapéutico , 17-Hidroxiesteroide Deshidrogenasas/antagonistas & inhibidores , 17-Hidroxiesteroide Deshidrogenasas/química , 17-Hidroxiesteroide Deshidrogenasas/metabolismo , 3-Hidroxiesteroide Deshidrogenasas/antagonistas & inhibidores , 3-Hidroxiesteroide Deshidrogenasas/química , 3-Hidroxiesteroide Deshidrogenasas/metabolismo , Animales , Biomarcadores/sangre , Biomarcadores/metabolismo , Suplementos Dietéticos/efectos adversos , Epidídimo/metabolismo , Epidídimo/patología , Infertilidad Masculina/etiología , Intoxicación por Plomo/metabolismo , Intoxicación por Plomo/patología , Intoxicación por Plomo/fisiopatología , Peroxidación de Lípido/efectos de los fármacos , Masculino , Tamaño de los Órganos/efectos de los fármacos , Compuestos Organometálicos/antagonistas & inhibidores , Compuestos Organometálicos/toxicidad , Sustancias Protectoras/efectos adversos , Sustancias Protectoras/uso terapéutico , Distribución Aleatoria , Ratas Wistar , Espermatogénesis/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Espermatozoides/patología , Testículo/metabolismo , Testículo/patología , Testosterona/sangre , Enfermedades Transmitidas por el Agua/metabolismo , Enfermedades Transmitidas por el Agua/patología , Enfermedades Transmitidas por el Agua/fisiopatología , Enfermedades Transmitidas por el Agua/prevención & control , Zinc/efectos adversosRESUMEN
OBJECTIVE: Lead (Pb) is a long-known poison of environment and industrial origin. Its prolonged exposure affects cellular material and alters cellular genetics and produces oxidative damages. In this study, we investigated the exposure of chronic sustained hypoxia or lead acetate alone or in combination with or without supplementation of α-tocopherol on hepatic oxidative and nitrosative stress in rats. MATERIALS AND METHODS: The rats weighing 165 ± 5 g were exposed to chronic sustained hypoxia (10% oxygen) or lead acetate (25 mg/kg of body weight, intraperitoneally) alone or in combination with or without supplementation of α-tocopherol (10 mg/100 g b.wt, intramuscularly). The body weight of all the rats was recorded on the day 1 of the treatment and the day of sacrifice. Serum lipid profile was estimated by using a biochemical analyzer. Oxidant and enzymatic antioxidants status was evaluated by using spectrophotometer. Serum levels of hypoxia inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) were measured by using ELISA technique. Histopathological assessments of hepatic tissue were also done. RESULTS: Exposure of both lead and hypoxia showed decreased body weight, altered serum lipid profile, oxidant and enzymatic antioxidants status, serum HIF-1α and VEGF concentrations. Simultaneous α-tocopherol supplementation showed beneficial effects to all these alterations. Histopathological observations also showed hepatic degenerative changes after lead or hypoxia exposure either alone or in combination, but remarkable improvement has been noticed after α-tocopherol supplementation. CONCLUSION: Supplementation of α-tocopherol is beneficial to counter both lead acetate and hypoxia induced hepatic cytotoxicities possibly by reducing oxidative and nitrosative stress.
Asunto(s)
Antioxidantes/farmacología , Hipoxia/prevención & control , Hepatopatías/prevención & control , Compuestos Organometálicos/antagonistas & inhibidores , Compuestos Organometálicos/toxicidad , alfa-Tocoferol/farmacología , Animales , Antioxidantes/administración & dosificación , Peso Corporal/efectos de los fármacos , Interacciones Farmacológicas , Hipoxia/sangre , Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/sangre , Lípidos/sangre , Hepatopatías/metabolismo , Hepatopatías/fisiopatología , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas , Factor A de Crecimiento Endotelial Vascular/sangre , alfa-Tocoferol/administración & dosificaciónRESUMEN
The effect of four trichlorotelluro-dypnones, named compounds 1, 2, 3, and 4, on the bioenergetics of isolated rat liver mitochondria (RLM) and cells was investigated. In a dose-dependent manner, the studied organotelluranes promoted Ca(2+)-dependent mitochondrial swelling inhibited by cyclosporine A and were associated with a decrease of the total mitochondrial protein thiol content. These effects characterize the opening of the classical mitochondrial permeability transition pore. Despite the reactivity with mitochondrial protein thiol groups, these compounds did not promote significant glutathione depletion. In the absence of Ca(2+), the organotelluranes promoted mitochondrial loss of ΔΨ in RLM concomitant with respiratory control decrease due to an increase of the state 4 respiration rate. In these conditions, mitochondrial swelling was absent, and thiol content was higher than that in the presence of Ca(2+). The differentiated effects observed in the presence and absence of Ca(2+) are probably related to the effects of that ion on membrane structure, with repercussions for the exposure of specific reactive protein thiol groups. In smooth muscle cells, these compounds promoted the loss of mitochondrial ΔΨ and apoptosis. The loss of ΔΨ was not preceded by a decrease of cell viability that is consistent with mitochondria as the primary targets for the action of these organotelluranes.
Asunto(s)
Chalconas/farmacología , Metabolismo Energético/efectos de los fármacos , Mitocondrias Hepáticas/efectos de los fármacos , Mitocondrias Hepáticas/metabolismo , Compuestos Organometálicos/farmacología , Compuestos de Sulfhidrilo/metabolismo , Animales , Calcio/metabolismo , Supervivencia Celular/efectos de los fármacos , Chalconas/antagonistas & inhibidores , Chalconas/química , Ciclosporina/farmacología , Relación Dosis-Respuesta a Droga , Masculino , Estructura Molecular , Compuestos Organometálicos/antagonistas & inhibidores , Compuestos Organometálicos/química , Ratas , Ratas Wistar , Relación Estructura-ActividadRESUMEN
It is well known that chronic exposure to lead (Pb(+2)) alters a variety of behavioral tasks in rats and mice. Here, we investigated the effect of flaxseed oil (1,000 mg/kg) on lead acetate (20 mg/kg)-induced brain oxidative stress and neurotoxicity in rats. The levels of Pb(+2), lipid peroxidation, nitric oxide (NO), and reduced glutathione (GSH) and the activity of catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione-S-transferase (GST), and glutathione peroxidase (GPx) were determined in adult male albino rats. The level of Pb(+2) was markedly elevated in brain and blood of rats. This leads to enhancement of lipid peroxidation and NO production in brain with concomitant reduction in GSH, CAT, SOD, GR, GST, and GPx activities. These findings were associated with DNA fragmentation. In addition, lead acetate induced brain injury as indicated by histopathological changes of the brain. Treatment of rats with flaxseed oil resulted in marked improvement in most of the studied parameters as well as histopathological features. These findings suggest to the conclusion that flaxseed oil significantly decreased the adverse harmful effects of lead acetate exposure on the brain as well as Pb(+2)-induced oxidative stress.
Asunto(s)
Intoxicación del Sistema Nervioso por Plomo/prevención & control , Aceite de Linaza/farmacología , Compuestos Organometálicos/antagonistas & inhibidores , Compuestos Organometálicos/toxicidad , Animales , Antioxidantes/metabolismo , Encéfalo/patología , Química Encefálica/efectos de los fármacos , Fragmentación del ADN/efectos de los fármacos , Glutatión/metabolismo , Plomo/sangre , Plomo/metabolismo , Intoxicación del Sistema Nervioso por Plomo/patología , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Nitratos/metabolismo , Nitritos/metabolismo , Ratas , Ratas WistarRESUMEN
Selenium (Se) has been demonstrated in previous studies to inhibit mammary tumorigenesis in C3H mice infected with the murine mammary tumorvirus, MMTV. The antitumorigenic effects of Se in this animal model of breast cancer were subsequently shown to be counteracted by Se-antagonistic elements. Lead (Pb), for example, was found to abolish the anticarcinogenic effects of Se at 5 ppm in the drinking water. The present study was undertaken to explore the effects of Pb at just 0.5 ppm in the water, i.e., at a level comparable to the concentrations of Pb that have been measured in the tap water of older homes in some communities. Groups of 30 female virgin C3H/St mice infected with MMTV maintained on Torula yeast-based diets containing either 0.15 or 0.65 ppm of yeast-based organic Se and received either deionized water or water containing 0.5 ppm Pb as the acetate over their entire postweaning lifespan. In the control group on deionized water and the 0.15 ppm Se feed, the tumor incidence was 78.6%, which is normal for this strain. Increasing the Se content of the feed to 0.65 ppm lowered the tumor incidence to 30%, demonstrating the antitumorigenic effect of Se. In the experimental groups, the Pb-exposed mice on the 0.15 ppm Se feed developed signs of chronic Pb toxicity as evidenced by diminished weight gain that persisted up to the age of 10 months, during which period the animals remained tumor-free. Thereafter, weight gains ensued to near the values of the controls, and the tumors began to develop in rapid succession until the final tumor incidence of 73.7% was reached. In the group of mice on the 0.65 ppm Se feed, the toxic effects of Pb were diminished, as evidenced by the normal weight gains during the first 10 months but with concomitant physiological inactivation of Se, causing 82.6% of the mice to develop tumors, with the first tumor to appear at the age of 5 months, 7 months earlier than in the Pb-unexposed controls. In addition, tumor growth rates in this group were greatly accelerated and the survival of the tumor-bearing animals was significantly shortened. Direct evidence for the interactions of Pb with Se were obtained by determinations of the two elements in the livers, kidneys, and hair of tumor-free and tumor-bearing mice. However, the exposure of the mice to Pb in the water also altered the levels of Zn, Cu, Fe, and Cr in the organs and tissues, more so in tumor-bearing than tumor-free animals. The present study demonstrates the need to consider the interactions of Se with other trace elements in discussions of its mechanism of anticarcinogenic action.
Asunto(s)
Antioxidantes/administración & dosificación , Transformación Celular Neoplásica/efectos de los fármacos , Neoplasias Mamarias Experimentales/prevención & control , Compuestos Organometálicos/antagonistas & inhibidores , Selenio/administración & dosificación , Animales , Transformación Celular Neoplásica/inducido químicamente , Transformación Celular Viral/efectos de los fármacos , Femenino , Neoplasias Mamarias Experimentales/inducido químicamente , Neoplasias Mamarias Experimentales/virología , Virus del Tumor Mamario del Ratón , Ratones , Ratones Endogámicos C3H , Compuestos Organometálicos/toxicidad , Oligoelementos/análisis , Aumento de Peso/efectos de los fármacosRESUMEN
Rats were treated with 0, 8, 16 and 24 mg/kg of lead acetate (LA) (i.p.) for 35 days with or without Maca. Maca was co-administrated orally from day 18 to day 35. The lengths of stages of the seminiferous epithelium were assessed by transillumination. Also, sex organ weights, testicular and epididymal sperm count, sperm motility, daily sperm production, sperm transit rate and serum testosterone levels were measured. Lead acetate treatment resulted in a dose-response reduction of lengths of stages VIII and IX-XI, and serum testosterone levels. However, rats treated with 8 and 16 mg/kg but not 24 mg/kg of lead acetate showed a low number of testicular spermatids, low daily sperm production (DSP) and low epididymal sperm count. Administration of Maca to rats treated with lead acetate resulted in higher lengths of stages VIII and IX-XI with respect to lead acetate-treated rats. Moreover, treatment with Maca to lead acetate-treated rats resulted in lengths of stages VIII and IX-XI similar to the control group. Maca administration also reduced the deleterious effect on DSP caused by lead acetate treatment. Maca prevented LA-induced spermatogenic disruption in rats and it may become in a potential treatment of male infertility associated with lead exposure.
Asunto(s)
Lepidium/química , Compuestos Organometálicos/antagonistas & inhibidores , Compuestos Organometálicos/toxicidad , Reproducción/efectos de los fármacos , Animales , Epidídimo/citología , Genitales Masculinos/efectos de los fármacos , Masculino , Tamaño de los Órganos/efectos de los fármacos , Extractos Vegetales/farmacología , Ratas , Ratas Sprague-Dawley , Recuento de Espermatozoides , Motilidad Espermática/efectos de los fármacos , Testosterona/sangreRESUMEN
Organochalcogens are important intermediates and useful reagents in organic synthesis, which can increase human exposure risk to these chemicals in the workplace. As well, there are a number of reported cases of acute toxicity following organochalcogen ingestion of vitamins and dietary supplements. Since, the erythrocytic delta-ALA-D activity could be an important indicator of toxicity this report investigated the organochalcogens effects on blood delta-ALA-D in vitro. To investigate a possible involvement of cysteinyl groups in the inhibitory actions of diphenyl diselenide, diphenyl ditelluride and Ebselen (4-100 micro M), the effects of thiol reducing agents (0-3 mM) or zinc chloride (0-2 mM) were examined. Diphenyl ditelluride, diphenyl diselenide and Ebselen inhibited in a concentration-dependent manner delta-ALA-D activity from human erythrocytes. Ebselen was lesser delta-ALA-D inhibitor than (PhSe)(2) and (PhTe)(2), whereas the diorganoyldichalcogenides displayed similar inhibitory potency towards delta-ALA-D. Dithiothreitol, a hydrophobic SH-reducing agent, was able to reactivate and to protect inhibited delta-ALA-D. The pre-incubation of blood with the inhibitors changed considerably the reversing potency of thiols. From these findings we suggest that organochalcogens inactivate in vitro human erythrocyte delta-ALA-D by an interaction with the sulfhydryl group essential of the enzyme activity.
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Antioxidantes/toxicidad , Azoles/toxicidad , Derivados del Benceno/toxicidad , Disulfuros/toxicidad , Eritrocitos/efectos de los fármacos , Compuestos Organometálicos/toxicidad , Compuestos de Organoselenio/toxicidad , Porfobilinógeno Sintasa/metabolismo , Azoles/antagonistas & inhibidores , Azoles/sangre , Derivados del Benceno/antagonistas & inhibidores , Derivados del Benceno/sangre , Cisteína/farmacología , Disulfuros/antagonistas & inhibidores , Disulfuros/sangre , Ditiotreitol/farmacología , Interacciones Farmacológicas , Eritrocitos/enzimología , Glutatión Transferasa/farmacología , Humanos , Isoindoles , Compuestos Organometálicos/antagonistas & inhibidores , Compuestos Organometálicos/sangre , Compuestos de Organoselenio/antagonistas & inhibidores , Compuestos de Organoselenio/sangre , Porfobilinógeno Sintasa/antagonistas & inhibidores , Zinc/farmacologíaRESUMEN
Curcumin (diferuloylmethane), an active ingredient of turmeric, is known to have multiple activities, including an antioxidant property, and has been suggested to be of use in treatment of several diseases. The present study has been undertaken to investigate the protective effect of curcumin against lead-induced neurotoxicity in rats. Exposure of rats to lead (50 mg/kg po) for 45 days caused an increase in lipid peroxidation (LPO) and a decrease in reduced glutathione (GSH) levels in cerebellum, corpus striatum, hippocampus and frontal cortex as compared with controls. Lead levels were significantly increased in these rats. Activity of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) decreased in all the brain regions following lead exposure. Interestingly, cotreatment with curcumin (100 mg/kg po) and lead (50 mg/kg po) for 45 days caused a significant decrease in LPO with concomitant decrease in lead levels in all the brain regions as compared with those treated with lead alone. A significant increase in reduced glutathione (GSH) levels, SOD and CAT activities was also observed in all the four brain regions in rats simultaneously treated with curcumin and lead. The results suggest that curcumin may prevent lead-induced neurotoxicity.
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Curcumina/uso terapéutico , Síndromes de Neurotoxicidad/tratamiento farmacológico , Compuestos Organometálicos/efectos adversos , Compuestos Organometálicos/antagonistas & inhibidores , Administración Oral , Animales , Catalasa/antagonistas & inhibidores , Catalasa/química , Cerebelo/química , Cerebelo/efectos de los fármacos , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/enzimología , Cuerpo Estriado/metabolismo , Curcumina/administración & dosificación , Curcumina/farmacocinética , Esquema de Medicación , Glutatión/antagonistas & inhibidores , Glutatión/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipocampo/enzimología , Hipocampo/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Peroxidación de Lípido/fisiología , Masculino , Corteza Motora/efectos de los fármacos , Corteza Motora/enzimología , Corteza Motora/metabolismo , Compuestos Organometálicos/farmacocinética , Ratas , Ratas Wistar , Superóxido Dismutasa/antagonistas & inhibidores , Superóxido Dismutasa/química , Sustancias Reactivas al Ácido Tiobarbitúrico/análisis , Factores de Tiempo , Distribución TisularRESUMEN
OBJECTIVE: To evaluate the effect of an aqueous extract of Phyllanthus niruri (Pn), a plant used in folk medicine to treat lithiasis, on the urinary excretion of endogenous inhibitors of lithogenesis, citrate, magnesium and glycosaminoglycans (GAGs). MATERIALS AND METHODS: The effect of chronic (42 days) administration of Pn (1.25 mg/mL/day, orally) was evaluated in a rat model of urolithiasis induced by the introduction of a calcium oxalate (CaOx) seed into the bladder of adult male Wistar rats. The animals were divided into four groups: a sham control (16 rats); a control+Pn (six); CaOx+water instead of Pn (14); and CaOx+Pn (22). Plasma and urine were collected after 42 days of treatment for biochemical analysis and the determination of urinary excretion of citrate, magnesium and GAGs. The animals were then killed and the calculi analysed. RESULTS: The creatinine clearance or urinary and plasma concentrations of Na+, K+, Ca2+, oxalate, phosphate and uric acid were unaffected by Pn or the induction of lithiasis. Treatment with Pn strongly inhibited the growth of the matrix calculus and reduced the number of stone satellites compared with the group receiving water. The calculi were eliminated or dissolved in some treated animals (three of 22). The urinary excretion of citrate and magnesium was unaffected by Pn treatment. However, the mean (sd) urinary concentration of GAGs was significantly lower in rats treated with CaOx+Pn, at 5.64 (0.86) mg/g creatinine, than when treated with CaOx + water, at 11.78 (2.21) mg/g creatinine. In contrast, the content of GAGs in the calculi was higher in the CaOx + Pn rats, at 48.0 (10.4) g/g calculus, than in the CaOx + water group, at 16.6 (9.6) g/g calculus. CONCLUSION: These results show that Pn has an inhibitory effect on crystal growth, which is independent of changes in the urinary excretion of citrate and Mg, but might be related to the higher incorporation of GAGs into the calculi.
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Oxalato de Calcio/antagonistas & inhibidores , Cálculos Renales/tratamiento farmacológico , Phyllanthus , Fitoterapia/métodos , Extractos Vegetales/uso terapéutico , Cálculos de la Vejiga Urinaria/tratamiento farmacológico , Animales , Ácido Cítrico/antagonistas & inhibidores , Cristalización , Glicosaminoglicanos/orina , Cálculos Renales/orina , Masculino , Compuestos Organometálicos/antagonistas & inhibidores , Fosfatos/sangre , Fosfatos/orina , Potasio/sangre , Potasio/orina , Ratas , Ratas Wistar , Sodio/sangre , Sodio/orina , Ácido Úrico/orina , Cálculos de la Vejiga Urinaria/orinaRESUMEN
Pure submandibular saliva was collected intraorally by micro polyethylene cannulation of anaesthetized rats using pilocarpine as a secretagogue. Twenty-four days treatment with lead acetate 0.05% in drinking water altered salivary function. Except for flow rate that was (P<0.01) increased by lead acetate, the reminder of parameters, concentrations of total protein and calcium and the activity of N-acetyl-beta-D-glucosaminidase (NAG) in submandibular secretions were decreased significantly (P<0.01) by lead acetate. Selenium (2.5 mg l(-1)) in drinking water for 24 days did not induce any significant change in saliva secretory function. Pretreatment by selenium, prevented the lead acetate-induced decrease of NAG activity and concentrations of calcium and protein (P<0.01). The increased flow rate by lead acetate was also affected by selenium pretreatment and reached the level of control. It is concluded that selenium can protect rat submandibular gland function from lead-acetate-induced adverse effects. Properties of selenium as an antioxidant, free radical scavenger and maintenance of cell membrane integrity may be possible mechanisms of its protective effects.
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Compuestos Organometálicos/antagonistas & inhibidores , Compuestos Organometálicos/toxicidad , Selenio/uso terapéutico , Glándula Submandibular/efectos de los fármacos , Acetilglucosaminidasa/metabolismo , Amilasas/metabolismo , Animales , Calcio/metabolismo , Masculino , Proteínas/metabolismo , Ratas , Ratas Sprague-Dawley , Saliva/química , Saliva/enzimología , Saliva/metabolismo , Salivación/efectos de los fármacos , Glándula Submandibular/enzimología , Glándula Submandibular/metabolismoRESUMEN
Male albino rats were intramuscularly administered a single dose of lead acetate (100 micromol/kg b.wt). Another group of rats were injected with sodium selenite (10 micromol/kg b.wt) before lead intoxication. After 3 and 24 hours, lead treatment resulted in significant increases in acid and alkaline phosphatases, GOT and GPT, total proteins, and cholesterol in serum. The total triglycerides in serum was decreased after 24 hours of intoxication. Lead treatment also produced significant elevation of lipid peroxidation in liver and kidney. The antioxidant capacity of hepatic and renal cells in terms of the activities of superoxide dismutase, glutathione reductase, and glutathione content was diminished. It appears from these results that lead may exert its toxic effect via peroxidative damage to renal and hepatic cell membranes after 24 hours. Selenium administration prior to lead injection produced pronounced prophylactic action against lead effects, and it is observed that selenium enhances the endogenous antioxidant capacity of the cells by increasing the activities of the superoxide dismutase and glutathione reductase and the glutathione content. As a result, the lipid peroxidation was decreased in both liver and kidney.
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Compuestos Organometálicos/antagonistas & inhibidores , Selenio/farmacología , Fosfatasa Ácida/sangre , Alanina Transaminasa/sangre , Fosfatasa Alcalina/sangre , Animales , Aspartato Aminotransferasas/sangre , Glutatión/metabolismo , Riñón/efectos de los fármacos , Riñón/enzimología , Riñón/metabolismo , Intoxicación por Plomo/sangre , Intoxicación por Plomo/prevención & control , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/enzimología , Hígado/metabolismo , Masculino , Compuestos Organometálicos/toxicidad , Ratas , Superóxido Dismutasa/metabolismoRESUMEN
In vitro administration of lead acetate (PbA) to cultures of Chinese hamster ovary (CHO) cells had a concentration-dependent inhibitory effect on colony formation. Colony formation was returned to control levels in lead-treated cultures that were supplemented with 1 mM N-actylcysteine (NAC), a well-documented synthetic antioxidant. In order to investigate the nature of NAC's protective effect, we measured L-gamma-glutamyl-L-cysteinylglycine (GSH), oxidized glutathione (GSSG), malondialdehyde (MDA) and catalase activity both in the presence and absence of NAC in lead-exposed CHO cells. Increases in both MDA levels (p < 0.05) and catalase activity (P < 0.05) were observed in cultures that received only PbA, but supplementation with NAC returned these measures to pretreatment levels. The ratio of GSH to GSSG increased in lead-exposed cells incubated in NAC-enhanced media, but declined in cultures treated with PbA only. Our results suggest that NAC can confer protection against lead-induced oxidative stress to CHO cells, possibly through the enhancement of the cell's own antioxidant defense mechanisms.
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Acetilcisteína/farmacología , Depuradores de Radicales Libres/farmacología , Plomo/antagonistas & inhibidores , Compuestos Organometálicos/antagonistas & inhibidores , Animales , Células CHO , Supervivencia Celular/efectos de los fármacos , Cricetinae , Contaminantes Ambientales , Glutatión/metabolismo , Plomo/toxicidad , Peroxidación de Lípido , Malondialdehído/metabolismo , Compuestos Organometálicos/toxicidad , Estrés Oxidativo/efectos de los fármacosRESUMEN
Female rats were administered intraperitoneal injections of solutions of lead acetate and sodium selenite. The salt solutions were given singly to 'control' animals and successively to the 'treated' animals in both chronic and acute treatments but with or without a time gap of 1 h in the latter treatment. In the chronic treatments the dosage of lead acetate was kept constant and that of sodium selenite varied while in the acute treatments the ratio of the two salts was kept constant. Degrees of protection afforded by sodium selenite against chromosomal damage caused by lead acetate were assessed.