RESUMEN
The aim of this study was to investigate the effects of inorganic mercury (Hg2+) exposure on biochemical parameters of dams and their offspring exposed to metal in drinking water. Female Wistar rats were exposed to 0, 10, and 50 µg Hg2+/mL (as HgCl2) for 42 days corresponding to gestational (21 days) and lactational (21 days) periods. The offspring were sacrificed on postnatal days 10, 20, 30, and 40. Dams exposed to Hg2+ presented a decrease in water intake in gestation [total: F(2,19) = 15.84; p ≤ 0.0001; daily: F(2,21) = 12.71; p = 0.0002] and lactation [total: F(2,19) = 4.619; p = 0.024; daily: F(2,21) = 5.309; p = 0.0136] without alteration in food intake. Dams exposed to 50 µg Hg2+/mL had an increase in kidney total [F(2,21) = 8.081; p = 0.0025] and relative [F(2,21) = 14.11; p = 0.0001] weight without changes in biochemical markers of nephrotoxicity. Moreover, dams had an increase in hepatic [F(2,10) = 3.847; p = 0.0577] and renal [F(2,11) = 6.267; p = 0.0152] metallothionein content concomitantly with an increase in renal Hg levels after Hg2+ exposure. Regarding offspring, the exposure to Hg2+in utero and breast milk increased the relative liver [F(2,18) = 5.33; p = 0.0152] and kidney [F(2,18) = 3.819; p = 0.0415] weight only on the postnatal day 40. In conclusion, dams were able to handle the Hg2+ avoiding the classic Hg2+ toxic effects as well as protecting the offspring. We suggest that this protection is related to the hepatic and renal metallothionein content increase.
RESUMEN
The aim of this work was to investigate the effects of HgCl2 exposure in the doses of 0, 10 and 50µg Hg2+/mL in drinking water during pregnancy on tissue essential metal homeostasis, as well as the effects of HgCl2 exposure in utero and breast milk on behavioral tasks. Pregnant rats exposed to both inorganic mercury doses presented high renal Hg content and an increase in renal Cu and hepatic Zn levels. Mercury exposure increased fecal Hg and essential metal contents. Pups exposed to inorganic Hg presented no alterations in essential metal homeostasis or in behavioral task markers of motor function. In conclusion, this work showed that the physiologic pregnancy and lactation states protected the offspring from adverse effects of low doses of Hg2+. This protection is likely to be related to the endogenous scavenger molecule, metallothionein, which may form an inert complex with Hg2+.
Asunto(s)
Metales Pesados/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , Animales Recién Nacidos , Conducta Animal/efectos de los fármacos , Agua Potable , Heces/química , Femenino , Feto/efectos de los fármacos , Feto/metabolismo , Homeostasis/efectos de los fármacos , Riñón/efectos de los fármacos , Riñón/metabolismo , Lactancia , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Metalotioneína/metabolismo , Metales Pesados/sangre , Metales Pesados/farmacocinética , Metales Pesados/orina , Placenta/efectos de los fármacos , Placenta/metabolismo , Embarazo , Ratas Wistar , Contaminantes Químicos del Agua/sangre , Contaminantes Químicos del Agua/farmacocinética , Contaminantes Químicos del Agua/orinaRESUMEN
Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment, associated with a reduced concentration of acetylcholine (ACh) in brain cortex and hippocampus. Recently we reported that the N-acetylcysteine (NAC) decreases brain acetylcholinesterase (AChE) activity in vitro. Thus, the aim of the current study was to investigate the effect of NAC against streptozotocin (STZ) induced AD in mice. Mice were divided into four groups: I) Sham, II) NAC, III) STZ and IV) NAC + STZ. Animals were daily treated with NAC (50 mg/kg/day, p.o.) for nine consecutive days and with STZ (2.5 mg/kg i.c.v.) at the first and third days. Step down passive avoidance (SDPA, days 7-8) and Morris water maze (MWM, days 6-9) task were assessed to evaluate learning and memory. On the tenth day animals were euthanized for AChE and butyrylcholinesterase (BChE) activities and ACh, energy-rich phosphate and brain glucose uptake levels evaluations. A learning and memory impairment was observed in SDPA and MWM in those animals that receive STZ. Nevertheless, the same was not observed in those animals that also received NAC. Brain cortex and hippocampus AChE and hippocampus BChE activities increase induced by STZ were also prevented by NAC treatment. The STZ induced a brain energy metabolism imbalance, decreasing adenosine triphosphate and increasing adenosine levels. The glucose uptake decrease in hippocampus was prevented by NAC. In conclusion, NAC treatment prevented the cognitive disturbance, by restoring the cholinergic system and brain energy metabolism disorders. NAC could modulate cholinergic imbalance without causing any changes per se in the same.
Asunto(s)
Acetilcisteína/farmacología , Memoria/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Estreptozocina/toxicidad , Acetilcolinesterasa/metabolismo , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Animales , Butirilcolinesterasa/metabolismo , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/enzimología , Metabolismo Energético/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipocampo/enzimología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , RatonesRESUMEN
This study evaluated the effects of HgCl2 on renal parameters in nonlactating and lactating rats and their pups, as well as the preventive role of ZnCl2 . Rats received 27 mg kg(-1) ZnCl2 for five consecutive days and 5 mg kg(-1) HgCl2 for five subsequent days (s.c.). A decrease in δ-aminolevulinic acid dehydratase (δ-ALA-D) activity in the blood and an increase in urine protein content in renal weight as well as in blood and urine Hg levels were observed in lactating and nonlactating rats from Sal-Hg and Zn-Hg groups. ZnCl2 prevented partially the δ-ALA-D inhibition and the proteinuria in nonlactating rats. Renal Hg levels were increased in all HgCl2 groups, and the ZnCl2 exposure potentiated this effect in lactating rats. Nonlactating rats exposed to HgCl2 exhibited an increase in plasma urea and creatinine levels, δ-ALA-D activity inhibition and histopathological alterations (necrosis, atrophic tubules and collagen deposition) in the kidneys. ZnCl2 exposure prevented the biochemical alterations. Hg-exposed pups showed lower body and renal weight and an increase in the renal Hg levels. In conclusion, mercury-induced nephrotoxicity differs considerably between lactating and nonlactating rats. Moreover, prior exposure with ZnCl2 may provide protection to individuals who get exposed to mercury occupationally or accidentally.
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Cloruros/farmacología , Riñón/efectos de los fármacos , Cloruro de Mercurio/toxicidad , Compuestos de Zinc/farmacología , Animales , Nitrógeno de la Urea Sanguínea , Peso Corporal/efectos de los fármacos , Creatinina/sangre , Femenino , Riñón/metabolismo , Riñón/patología , Lactancia , Mercurio/sangre , Porfobilinógeno Sintasa/metabolismo , Proteínas/análisis , Ratas , Ratas Wistar , Zinc/sangreRESUMEN
This work investigated the effects of low and high doses of inorganic mercury in drinking water on biochemical parameters of pregnant rats and their offspring. Female Wistar rats were treated during pregnancy with 0, 0.2, 0.5, 10 or 50 µg Hg(2+)/mL as HgCl(2). Rats were euthanized on day 20 of pregnancy. Pregnant rats presented a decrease in total water intake in all doses of mercury tested. At high doses, a decrease in the total food intake and in body weight gain was observed. Pregnant rats exposed to 50 µg Hg(2+)/mL presented an increase in kidney relative weight. Mercury exposure did not change serum urea and creatinine levels in any of the doses tested. Moreover, mercury exposure did not change porphobilinogen synthase activity of kidney, liver and placenta from pregnant rats in any of the doses tested, whereas fetuses of pregnant rats exposed to 50 µg Hg(2+)/mL presented an increase in the hepatic porphobilinogen synthase activity. In general, pregnant rats presented alterations due to HgCl(2) exposure in drinking water. However, only the dose 50 µg Hg(2+)/mL appeared to be enough to cross the blood-placenta barrier, since at this dose the fetuses presented change in the porphobilinogen synthase activity.
Asunto(s)
Exposición Materna , Mercurio/toxicidad , Abastecimiento de Agua , Animales , Conducta Alimentaria/efectos de los fármacos , Femenino , Embarazo , Ratas , Ratas Wistar , Aumento de Peso/efectos de los fármacosRESUMEN
The aim of this study was to evaluate lipid peroxidation, protein oxidation and activity of enzymes that are indicators of oxidative stress in Rangelia vitalii infection in dogs. Animals were divided into two groups: negative control (n=5) and infected with R. vitalii (n=7). After inoculation, the parasitemia was estimated daily by microscopic examination of smears. Lipid peroxidation (TBARS) and advanced oxidation protein products (AOPP); and delta-aminolevulinate dehydratase (δ-ALA-D), superoxide dismutase (SOD) and catalase (CAT) activities in blood were evaluated. The samples were collected at days 10 and 20 post-inoculation (PI). TBARS and AOPP levels were higher in the infected group in both analyzed periods (P<0.01). The δ-ALA-D activity was reduced in blood of dogs infected with R. vitalii on days 10 and 20 PI. SOD activity was significantly increased (P<0.01) in the blood of dogs infected with R. vitalii at days 10 and 20 PI, while CAT activity was significantly increased (P<0.01) only at day 20 PI when compared to non-infected animals. A positive correlation was observed between the degree of parasitemia and TBARS and AOPP levels and activity of antioxidant enzymes. The δ-ALA-D activity was negatively correlated with the degree of parasitemia. Based on the increased levels of TBARS, AOPP, SOD and CAT activities, and inhibition δ-ALA-D activity, we concluded that dogs experimentally infected with R. vitalii develop a state of redox unbalance and that these changes might be involved in the pathophysiology of disease.
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Apicomplexa/fisiología , Enfermedades de los Perros/parasitología , Estrés Oxidativo/fisiología , Infecciones Protozoarias en Animales/parasitología , Productos Avanzados de Oxidación de Proteínas/metabolismo , Animales , Apicomplexa/clasificación , Catalasa/genética , Catalasa/metabolismo , Perros , Femenino , Regulación Enzimológica de la Expresión Génica , Parasitemia , Porfobilinógeno Sintasa/genética , Porfobilinógeno Sintasa/metabolismo , Infecciones Protozoarias en Animales/patología , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
The aim of this study was to evaluate the activity of delta-aminolevulinate dehydratase (δ-ALA-D) in red blood cells of rats infected with Trypanosoma evansi and establish its association with haematocrit, serum levels of iron and zinc and lipid peroxidation. Thirty-six male rats (Wistar) were divided into 2 groups with 18 animals each. Group A was non-infected while Group B was intraperitoneally infected, receiving 7·5×106 trypomastigotes per animal. Each group was divided into 3 subgroups of 6 rats and blood was collected during different periods post-infection (p.i.) as follows: day 5 (A1 and B1), day 15 (A2 and B2) and day 30 PI (A3 and B3). Blood samples were collected by cardiac puncture to estimate red blood cell parameters (RBC), δ-ALA-D activity and serum levels of iron, zinc and thiobarbituric acid reactive substances (TBARS). Rats in group B showed a significant (P<0·05) reduction of RBC count, haemoglobin concentration and haematocrit at days 5 and 15 p.i. The activity of δ-ALA-D in blood was significantly (P<0·001) increased at days 15 and 30 p.i. δ-ALA-D activity in blood had a significant (P<0·05) negative correlation with haematocrit (r=-0·61) and haemoglobin (r=-0·70) at day 15 p.i. There was a significant (P<0·05) decrease in serum iron and zinc levels and an increase in TBARS levels (P<0·05) during infection. The δ-ALA-D activity in blood was negatively correlated with the levels of iron (r=-0·68) and zinc (r=-0·57) on day 30 p.i. It was concluded that the increased activity of δ-ALA-D in blood might have occurred in response to the anaemia in remission as heme synthesis was enhanced.
Asunto(s)
Anemia/enzimología , Porfobilinógeno Sintasa/sangre , Trypanosoma/fisiología , Tripanosomiasis/enzimología , Anemia/sangre , Anemia/complicaciones , Anemia/parasitología , Animales , Recuento de Eritrocitos , Eritrocitos/química , Hematócrito , Hemoglobinas/análisis , Hierro/análisis , Peroxidación de Lípido , Masculino , Parasitemia/sangre , Ratas , Ratas Wistar , Espectrofotometría , Sustancias Reactivas al Ácido Tiobarbitúrico/análisis , Tripanosomiasis/sangre , Tripanosomiasis/complicaciones , Tripanosomiasis/parasitología , Zinc/análisisRESUMEN
Ebselen is a seleno compound whose antioxidant properties have been attributed to its thiol-peroxidase and thioredoxin-like activity. However, the excessive oxidation of thiols can be potentially toxic. Thus, this work investigated whether lactate dehydrogenase (LDH) can be a possible in vitro target to the toxicity of ebselen, in comparison with diphenyl diselenide [(PhSe)(2)] and diphenyl ditelluride [(PhTe)(2)]. Ebselen was the most potent inhibitor of LDH. A maximal inhibitory effect was obtained at 2 µM to LDH purified and at 20 µM to LDH from heart and liver homogenates. Moreover, (PhSe)(2), followed by (PhTe)(2), also presented a significant inhibitory effect on LDH activity. DL-dithiothreitol (DTT) was able to revert the inhibition of LDH induced by all compounds tested, confirming the involvement of essential thiol groups on LDH inhibition by organochalcogens. In conclusion, our results show that liver and heart LDH may be a possible target for the toxicity of organochalcogens at relative low concentrations. Our results also indicate that the use of LDH, as a marker of cell viability, may be biased by a direct inhibitory effect of ebselen or other chalcogenides on LDH, resulting in false protection in an in vitro system.
Asunto(s)
Antioxidantes/toxicidad , Azoles/toxicidad , Derivados del Benceno/toxicidad , L-Lactato Deshidrogenasa/antagonistas & inhibidores , Compuestos Organometálicos/toxicidad , Compuestos de Organoselenio/toxicidad , Animales , Antioxidantes/química , Azoles/química , Derivados del Benceno/química , Biomarcadores/análisis , Ditiotreitol/farmacología , Relación Dosis-Respuesta a Droga , Corazón/efectos de los fármacos , Isoindoles , Hígado/efectos de los fármacos , Hígado/enzimología , Masculino , Estructura Molecular , Miocardio/enzimología , Compuestos Organometálicos/química , Compuestos de Organoselenio/química , Ratas , Compuestos de Sulfhidrilo/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The infusion or decoction of Mirabilis jalapa leaves is used in traditional medicine in Brazil to treat inflammatory and painful diseases. AIM OF THE STUDY: The present study examined the antinociceptive effect of Mirabilis jalapa extracts from leaves and stems in models of pain in mice. MATERIALS, METHODS AND RESULTS: The crude hydroethanolic extract from leaves (CrdL) was more potent than the crude extract from stems (CrdS) to inhibit abdominal constrictions induced by acetic acid, with ID(50) values of 5.5 (2.3-13.1) and 18.0 (11.3-28.5) mg/kg, respectively. Among the fractions tested, the Eta fraction from leaves (Eta) was more effective (maximal inhibition of 83+/-8%) and potent (ID(50) of 1.1 (0.6-2.1) mg/kg) to induce antinociception. Eta and CrdL also possessed an antinociceptive effect in the tail-flick test. Pre-treatment with naloxone did not modify the antinociceptive effect of Eta, but co-administration with atropine completely prevented it. This suggests that the antinociceptive effect might depend on the cholinergic system. Instead, Eta was not able to alter the acetylcholinesterase activity in blood or spinal cord. Concerning side effects, Eta did not alter locomotor activity, body temperature, gastrointestinal transit and did not produce gastric lesions. CONCLUSION: Our results demonstrate that Mirabilis jalapa presents antinociceptive activity in mice, which supports its folkloric use as an analgesic.
Asunto(s)
Analgésicos/administración & dosificación , Mirabilis/química , Dolor/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Acetilcolinesterasa/efectos de los fármacos , Acetilcolinesterasa/metabolismo , Analgésicos/aislamiento & purificación , Analgésicos/toxicidad , Animales , Atropina/farmacología , Temperatura Corporal/efectos de los fármacos , Brasil , Modelos Animales de Enfermedad , Tránsito Gastrointestinal/efectos de los fármacos , Concentración 50 Inhibidora , Masculino , Medicina Tradicional , Ratones , Actividad Motora/efectos de los fármacos , Naloxona/farmacología , Dimensión del Dolor , Extractos Vegetales/toxicidad , Hojas de la Planta , Tallos de la Planta , Pruebas de ToxicidadRESUMEN
This paper shows the toxicity of mercury (HgCl(2) 5mg/kg/day for 5 days, sc) applied at specific stages of development (1-5, 8-12 or 17-21 days old, 1st, 2nd and 3rd phases, respectively) on the performance of rats in three behavioral tasks and on cerebral mercury levels. The mercury exposure at the 1st and 2nd phases affected the performances of rats in the rim escape. Spontaneous alternation behavior was not altered by mercury exposure. In the open field task, habituation was absent when the rats were treated at the 1st phase, and the crossing response number was lower in rats exposed to mercury at the last period. In general, the brain accumulated large quantities of mercury. In short, the first days of postnatal life (1st phase) appeared to be more sensitive to mercury exposure than the other phases studied, since they presented behavioral deficits even at a time period somewhat after the exposure.
Asunto(s)
Conducta Animal/efectos de los fármacos , Desinfectantes/toxicidad , Cloruro de Mercurio/toxicidad , Factores de Edad , Análisis de Varianza , Animales , Animales Recién Nacidos , Peso Corporal/efectos de los fármacos , Reacción de Fuga/efectos de los fármacos , Conducta Exploratoria/efectos de los fármacos , Aprendizaje por Laberinto/efectos de los fármacos , Ratas , Ratas Wistar , Distribución TisularRESUMEN
Os serviços de hemoterapia no Brasil são, atualmente, regulamentados segundo a RDC-343. Indivíduos fumantes apresentam, em geral, níveis de HT e Hb dentro dos valores de referência para doação de sangue. Considerando que estes valores estão em uma faixa ampla, o presente trabalho avaliou a qualidade do sangue utilizado para doação quanto a estes parâmetros hematológicose quanto à atividade das enzimas sanguíneas PBG-sintase e colinesterase, às quais, têm sido utilizadas como biomarcadores de exposição e/ou intoxicação por agentes oxidantes e inseticidas, respectivamente. Estes parâmetros foram analisados em 30 amostras,divididas em três grupos: NF não fumantes; F10 fumantes de 10±5 cigarros/dia; e, F20 fumantes de 20 ou mais cigarros/dia. Os resultados demonstram que os níveis de HT e Hb apresentaram-se significativamente aumentados no grupo F20, e os níveis de COHb, aumentados em ambos os grupos fumantes (F10 e F20). Quanto às enzimas em estudo, o tabagismo não alterou suas atividades. O grupo F20 apresentou atividade da PBG-sintase e índice de reativação ligeiramente diminuídos. A atividade colinesterásica apresentou um aumento de 18% no grupo F20, porém, não significativo. De acordo com os resultados obtidos faz-se necessário aprofundar os estudos sobre a qualidade do sangue utilizado nos serviços de hemoterapia brasileiro...
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Humanos , Colinesterasas , Hematología , Toxicología , Análisis Químico de la Sangre , Fumar , NicotianaRESUMEN
A number of C(4)-C9 aliphatic ketones, including 2,5-hexanedione (2,5-HD), are acetylcholinesterase (AChE; EC 3.1.1.7) inhibitors. In the previous work, we demonstrated that antinociception induced by 2,5-HD was partially reversed by atropine. Since cholinergic system seems to be affected by hexacarbon compounds, in the present study we examined the effect of 2,5-HD on AChE activity of rat brain in vitro. The results demonstrated that both Km and Vmax were altered by 2,5-HD. At 5 mM 2,5-HD, there were no significant changes in Km or Vmax parameters, but at concentrations higher than 10 mM an increase in Km and a decrease in Vmax was observed. The Ki plot was linear and the curves intersect on the left of the 1/V versus [I] plot. These data characterize an inhibition of the mixed type. Although the 2,5-HD concentration that inhibited AChE activity is high compared to that attainable in occupationally exposed workers, these data are useful in understanding the neurotoxicity of this compound. Furthermore, the effect of 2,5-HD on AChE activity must not be a consequence of its effects as an organic solvent on protein structure, because total inhibition induced by 2,5-HD was partially reversed by increasing substrate concentration.
Asunto(s)
Encéfalo/enzimología , Inhibidores de la Colinesterasa/toxicidad , Hexanonas/toxicidad , Acetilcolinesterasa/metabolismo , Animales , Encéfalo/efectos de los fármacos , Cinética , Masculino , Ratas , Ratas WistarRESUMEN
The effects of CdCl2 and ZnCl2 pretreatments on the inhibition of delta-ALA-D (delta-aminolevulinic acid dehydratase) activity and Hg contents in liver and kidneys of suckling rats intoxicated with HgCl2 were investigated. Zn-pretreatment prevented the effects of mercury at a higher magnitude than CdCl2. Hepatic and renal delta-ALA-D activities were significantly inhibited by HgCl2 and prior exposure to CdCl2 partially prevented the renal effect of mercury but not altered the mercury levels in both tissues. Pretreatment with ZnCl2 abolished mercury-induced delta-ALA-D-inhibition in kidneys and liver and induced an increase in renal (about three times) and a decrease in hepatic (to one-third) Hg contents when compared to the group injected only with mercury. In face of zinc effects to prevent Hg-delta-ALA-D inhibition and to alter Hg-deposition levels in kidney and liver, these results suggest that these effects may be partially due to the synthesis of metallothioneins (MT). In fact, liver MT content presented by animals pretreated with zinc was significantly greater than control and Hg-treated groups, but the increase showed by renal tissue (about 60%) was not significant. Although the MT is rich in cysteine (-SH) and consequently can form a great number of MT-Hg complex, other mechanisms should be also involved in zinc protection on mercury toxicity.