RESUMEN
Mercury (Hg), a divalent metal, produces adverse effects predominantly in the renal and central nervous systems. The aim of this study was to determine the effectiveness of copper (Cu) in prevention of mercuric mercury (Hg2+)-mediated toxic effects as well as the role metallothioneins (MT) play in this protective mechanism in young rats. Wistar rats were treated subcutaneously with saline (Sal) or CuCl2.2H2O (Cu 2.6 mg/kg/day) from 3 to 7 days old and with saline or HgCl2 (Hg 3.7 mg/kg/day) from 8 to 12 days old. The experimental groups were (1) Sal-Sal, (2) Cu-Sal, (3) Sal-Hg, and (4) Cu-Hg. MTs and metal contents were determined at 13 and 33 days of age. Porphobilinogen synthase (PBG-synthase) activity as well as renal and hepatic parameters were measured at 33 days. At 13 day, Hg2+ exposure increased hepatic MT, Hg, zinc (Zn) and iron (Fe) levels, in kidney elevated Cu and Hg and decreased renal Fe concentrations, accompanied by elevated blood Hg levels. At 33 days, Hg2+ exposure inhibited renal PBG-synthase activity, increased serum urea levels and lowered Fe and Mg levels. Copper partially prevented the rise in blood Hg and liver Fe noted at 13 days; and completely blocked urea rise and diminished renal PBG-synthase activity inhibition at 33 days. In 13-day-old rats, Cu exposure redistributed the Hg in the body, decreasing hepatic and blood levels while increasing renal levels, accompanied by elevated renal and hepatic MT levels in Hg2+-exposed animals. These results suggest that hepatic MT might bind to hepatic and blood Hg for transport to the kidney in order to be excreted. ABBREVIATIONS: MT: metallothioneins; PBG-synthase: porphobilinogen synthase.
Asunto(s)
Cobre/farmacología , Cloruro de Mercurio/toxicidad , Intoxicación del Sistema Nervioso por Mercurio/prevención & control , Metalotioneína/metabolismo , Sustancias Protectoras/farmacología , Animales , Animales Recién Nacidos , Cloruro de Mercurio/envenenamiento , Ratas , Ratas Wistar , Oligoelementos/farmacologíaRESUMEN
This work investigated zinc (Zn) and mercury (Hg) effects on oxidative parameters, markers of toxicity and metal levels in different tissues from non-lactating rats (NLR) and lactating rats (LR). Adult NLR and LR received ZnCl2 (27mg/kg) or saline (0.9%) subcutaneously and after 24h they received HgCl2 (5mg/kg) or saline (0.9%). Twenty four hours later, they were sacrificed and the preparation of biological material and biochemical analyses were performed. With respect to oxidative parameters, Hg exposure decreased kidney total SH levels from NLR and LR and hepatic catalase activity (not statistically significant) in NLR. Zinc pre-treatment partly prevented the decrease of kidney total SH levels in LR. Zinc per se increased hepatic non-protein SH levels of NLR and LR. Regarding toxicity markers, Hg exposure inhibited the δ-aminolevulinic acid dehydratase (δ-ALA-D) activity from kidney and liver of NLR, inhibited serum alanine aminotransferase (ALT) activity of LR and increased serum creatinine and urea levels of NLR and LR. Zinc pre-exposure prevented the enzymatic alterations caused by Hg. NLR and LR Hg exposed presented accumulation of mercury in the kidney, liver, blood and urine. Zinc pre-treatment prevented this accumulation partly in NLR liver and blood and completely in LR kidney and liver. These results show that NLR and LR are differently sensitive to HgCl2 and that ZnCl2 showed a promising effect against Hg toxicity.
Asunto(s)
Cloruros/farmacología , Lactancia/efectos de los fármacos , Cloruro de Mercurio/toxicidad , Sustancias Protectoras/farmacología , Compuestos de Zinc/farmacología , Alanina Transaminasa/sangre , Animales , Ácido Ascórbico/metabolismo , Catalasa/metabolismo , Creatinina/sangre , Femenino , Riñón/efectos de los fármacos , Riñón/enzimología , Lactancia/sangre , Hígado/efectos de los fármacos , Hígado/enzimología , Especificidad de Órganos/efectos de los fármacos , Porfobilinógeno Sintasa/sangre , Ratas Wistar , Compuestos de Sulfhidrilo/metabolismo , Urea/sangreRESUMEN
The aim of the present study was to evaluate the possible effects of zinc chloride against the gastrointestinal lesions caused by oral administration of ethanol in rats. Rats were divided into five groups, namely, saline, ethanol, zn, zn+ethanol and ethanol+zn. Ethanol 70% (2 mL/kg) was administered by gavage in 36 h fasted rats. Zinc chloride (27 mg/kg, ~13 mg/kg of zinc) was given by gavage 1h before or 1h after the administration of ethanol. Oral administration of ethanol consistently induced damage in the rat glandular stomach and intestine. Zinc did not demonstrate effect per se and significantly reduced gastrointestinal lesions when administered either before or after lesion induction. Ethanol induced enhancement of thiobarbituric acid reactive substance and reactive species levels, diminished the ascorbic acid and total protein SH content as well as superoxide dismutase and catalase activity in stomach and intestine of rats. Zinc treatment prevented and reversed these alterations induced by ethanol. Stomach and intestine of rats treated with zinc presented higher zinc content than the tissues of rats treated only with ethanol. Non-protein SH content was not altered by any treatment. Results suggested that the gastrointestinal protective effect of zinc in this experimental model could be due to its antioxidant effect.
Asunto(s)
Antioxidantes/farmacología , Cloruros/farmacología , Etanol/toxicidad , Mucosa Gástrica/efectos de los fármacos , Compuestos de Zinc/farmacología , Animales , Ácido Ascórbico/metabolismo , Catalasa/metabolismo , Mucosa Gástrica/enzimología , Mucosa Gástrica/metabolismo , Peroxidación de Lípido , Masculino , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Compuestos de Sulfhidrilo/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
This work investigated the effects of copper as preventive treatment against mercury-induced alterations in young rats. Wistar rats were treated (subcutaneous) with saline or CuCl(2) · 2H(2) O (6.9 mg/kg/day) from 3 to 7 days old and with saline or HgCl(2) (5.0 mg/kg/day) from 8 to 12 days old. Rats were sacrificed 24 h after the last dose. Mercury-exposed rats presented inhibition of liver (43%) and kidney (52%) porphobilinogen (PBG)-synthase activity and serum lactic dehydrogenase activity (50%). Also, an increase of the serum creatinine and urea levels around threefold and fivefold was observed, respectively. Pre-exposure to copper partially prevented the mercury effect on liver but not on kidney PBG synthase, and prevented the increase of the creatinine levels. Blood and brain PBG synthase and serum alanineaminotransferase activities, as well as glycemia, and liver glycogen content were not altered by treatments. These results show that copper, although being an essential metal, is inefficient as a preventive agent against mercury poisoning in parameters investigated after the end of mercury exposure.
Asunto(s)
Cobre/farmacología , Cloruro de Mercurio/toxicidad , Sustancias Protectoras/farmacología , Animales , Animales Recién Nacidos , Anoctaminas , Glucemia , Nitrógeno de la Urea Sanguínea , Peso Corporal/efectos de los fármacos , Encéfalo/enzimología , Canales de Cloruro , Cobre/uso terapéutico , Creatinina/sangre , Relación Dosis-Respuesta a Droga , Glucógeno/metabolismo , Riñón/efectos de los fármacos , Riñón/enzimología , Hígado/efectos de los fármacos , Hígado/enzimología , Tamaño de los Órganos/efectos de los fármacos , Porfobilinógeno Sintasa/sangre , Porfobilinógeno Sintasa/metabolismo , Sustancias Protectoras/uso terapéutico , Ratas WistarRESUMEN
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
This work investigated the in vivo and in vitro effects of HgCl2 and ZnCl2 on metabolic enzymes from tissues of young rats to verify whether the physiological and biochemical alterations induced by mercury and prevented by zinc are related to hepatic and renal glucose metabolism. Wistar rats received (subcutaneous) saline or ZnCl2 (27 mg/kg/day) from 3 to 7 days old and saline or HgCl2 (5.0 mg/kg/day) from 8 to 12 days old. Mercury exposure increased the hepatic alanine aminotransferase (â¼6-fold) and glucose 6-phosphatase (75%) activity; zinc pre-exposure prevented totally and partially these mercury alterations respectively. In vitro, HgCl2 inhibited the serum (22%, 10 µM) and liver (54%, 100 µM) alanine aminotransferase, serum (53%) and liver (64%) lactate dehydrogenase (10 µM), and liver (53%) and kidney (41%) glucose 6-phosphatase (100 µM) from 10- to 13-day-old rats. The results show that mercury induces distinct alterations in these enzymes when tested in vivo or in vitro as well as when different sources were used. The increase of both hepatic alanine aminotransferase and glucose 6-phosphatase activity suggests that the mercury-exposed rats have increased gluconeogenic activity in the liver. Zinc prevents the in vivo effects on metabolic changes induced by mercury.