Maria L. Albina

Influence of Maternal Stress on the Effects of Prenatal Exposure to Methylmercury and Arsenic on Postnatal Development and Behavior in Mice: A Preliminary Evaluation

The present study combined maternal restraint stress with exposure to 2 environmental toxic elements, mercury and arsenic, given to mice concurrently with the restraint period (1000-1200 h, gestational days 15-18). Two groups of animals were given, by gavage, methylmercury chloride (MMC) (2 mg/kg/day), and 2 additional groups received sodium arsenite (10 mg/kg/day) on days 15-18 of gestation. Immediately after MMC or arsenite exposure, 1 group of MMC-treated mice and 1 group of arsenite-treated animals were restrained for 2 h/day. Control groups included restrained and unrestrained pregnant mice nonexposed to MMC or arsenite. All animals were allowed to deliver and wean their offspring. Pups were evaluated for physical development, as well as for behavioral effects. Except for a significant decrease in pivoting on postnatal day 9 in the group exposed to arsenite plus restraint, no other MMC- or arsenite-induced behavioral changes were noted in unrestrained or restrained groups. Although a significant delay in pinna detachment and in eye opening was observed in pups of the group exposed to arsenite and restraint, the development landmarks were not affected by restraint in the MMC-treated animals. Although maternal stress reduced body weight gain in the dams exposed to MMC plus restraint, a significant interaction between maternal stress and MMC could not be established for developmental toxicity. These preliminary results, combined with those of previous investigations, show that stress can significantly exacerbate the adverse effects of environmental toxic elements.

Effects of BDE-99 on hormone homeostasis and biochemical parameters in adult male rats

In this study, we evaluated the effects of BDE-99 on hormone homeostasis, as well as in urinary and serum biochemical parameters of adult male rats. Animals (10 per group) received BDE-99 by gavage at single doses of 0, 0.6 and 1.2mg/kg. Forty-five days after BDE-99 exposure, urine and serum samples were collected for hormonal and biochemical analysis. Oxidative stress (OS) markers in erythrocytes, plasma and urine were also evaluated. Urinary excretion of total protein significantly increased following BDE-99 exposure, while lactate dehydrogenase (LDH), gamma-glutamil transferase (GGT), and N-acetylglucosaminidase (NAG) activities significantly decreased. Liver toxicity was evidenced by elevated serum activities of the enzymes glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) and alkaline phosphatase (ALP). Following BDE-99 administration, OS markers in erythrocytes showed an increase in superoxide dismutase (SOD) activity, and a reduction in glutathione reductase (GR) activity. In urine, isoprostane levels increased after BDE-99 exposure. The hormonal analysis showed a significant decrease in testosterone and progesterone levels. These results support the hypothesis that BDE-99 interacts with hormonal response. Moreover, BDE-99 administration to adult male rats showed signs of renal and hepatic toxicity.

Effects of maternal stress on methylmercury-induced developmental toxicity in mice

The developmental toxicity of combined exposure to maternal restraint stress and methylmercury chloride (MMC) was assessed in Swiss mice. On day 10 of gestation, four groups of plug-positive female mice were treated (p.o.) with a single dose of 12.5 or 25 mg MMC/kg. Immediately after MMC exposure, two of those groups were subjected to restraint for 14 hr. Control groups included restrained and unrestrained pregnant mice nonexposed to MMC. Combined exposure to 25 mg MMC/kg and restraint enhanced MMC-induced maternal toxicity, which included deaths and decreased body weight gain and food consumption. The number of nonviable implants was also increased significantly following concurrent exposure to MMC (25 mg/kg) and restraint, with the percentage of postimplantation loss increased from 64% (MMC alone) to 100% (MMC plus restraint). However, the types and incidence of internal and skeletal anomalies observed after administration of 12.5 mg MMC/kg were not increased by maternal restraint. These results suggest that maternal stress would enhance the MMC-induced maternal and embryo/fetal toxicity at doses of MMC that are highly toxic to the dams, whereas at doses that are less acutely toxic the role of maternal stress would not be significant.

Sulfasalazine induced oxidative stress: A possible mechanism of male infertility

The mechanism of action of sulfasalazine (SASP) in male infertility is not well elucidated. For it, an oxidative stress-like mechanism inductor of infertility was hypothesized. Adult male Sprague-Dawley rats (20/group) were orally administered 0, 300, and 600mg SASP/kg body weight for 14 days. One-half of animals in each group remained an additional period of 14 days without treatment. SASP induced a significant decrease of superoxide dismutase (SOD) and glutathione reductase (GR) at the highest dose in both testis and epididymis. GR remained altered in these tissues within the recovery period. However, an increase in SOD was noted in epididymis. An increase in thiobarbituric acid-reactive substances (TBARS) was noted in all SASP-treated groups. In epididymis, catalase (CAT) significantly increased at 600mg/(kgday). These results suggest that SASP induces oxidative stress, which in turn might act as a possible mechanism of male-induced infertility.

Lipid peroxidation and antioxidant status in kidney and liver of rats treated with sulfasalazine

Sulfasalazine (SASP) is a drug commonly used in the treatment of inflammatory bowel diseases (IBD). In this study, the changes in endogenous antioxidant capacity and oxidative damage in liver and kidney of SASP-treated rats were investigated. Adult male Sprague-Dawley rats were orally given 0, 300, or 600 mg SASP/kg body weight for 14 days. One half of the animals in each group remained 14 additional days without SASP treatment. At the end of the experimental period, rats were euthanized and liver and kidney were removed. In both organs, the following stress markers were determined: reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and thiobarbituric acid-reactive substances (TBARS). Moreover, histological examination of kidneys showed phagolysosomes after 14 days of SASP withdrawal. A dropsical degeneration was also observed in renal tissue. Oral SASP administration induced a significant increase in TBARS levels in both liver and kidney. After 2 weeks without SASP administration, a recovery of these levels was noted. SOD activity was significantly reduced, while CAT activity significantly increased at 600 mg SASP/(kg day). In kidney, GPx activity significantly increased, while GST activity and GSH levels were significantly reduced at 600 mg SASP/(kg day). These results suggest that in male rats, oxidative damage can be a mechanism for nephro- and hepatotoxicity related with SASP treatment.

Influence of maternal restraint stress on arsenic-induced pre- and postnatal alterations in mice

The potential interaction between arsenic and maternal stress was assessed in Swiss mice. Two groups of pregnant animals were given by gavage a single dose of 30-mg/kg sodium arsenite on gestation Day 7. Mice in one of the groups were subjected to restraint for 2 h per day on gestation Days 7–9. Control groups included restrained and unrestrained pregnant mice nonexposed to arsenite. One half of the animals were euthanized on gestational Day 18 and fetuses were examined for embryotoxic and teratogenic effects. The remaining dams were allowed to deliver and wean their offspring. Pups were evaluated with a multiitem neurobehavioral test battery. Although arsenite-induced maternal toxicity was enhanced by restraint, there were no significant effects of maternal stress on embryo/fetal toxicity or on most neurobehavioral parameters. According to these results, maternal restraint stress would not enhance the developmental and neurobehavioral toxicity of arsenite in mice at oral doses that are not teratogenic by themselves.

Oxidative stress markers after a race in professional cyclists.

The aim was to determine the levels and activities of the oxidative stress markers in erythrocytes, plasma, and urine after a flat cyclist stage. Eight voluntary male professional trained-cyclists participated in the study. Exercise significantly increased erythrocyte, leukocyte, platelet, and reticulocyte counts. The exercise induced significant increases in the erythrocyte activities of catalase (19.8%) and glutathione reductase (19.2%), while glutathione peroxidase activity decreased significantly (29.3%). Erythrocyte GSSG concentration was significantly increased after exercise (21.4%), whereas GSH was significantly diminished (20.4%). Erythrocyte malondialdehyde levels evidenced a significant decrease 3 h after finishing the stage (44.3%). Plasma malondialdehyde, GSH and GSSG levels significantly decreased after 3 hr recovery (26.8%, 48.6%, and 31.1%, respectively). The exercise significantly increased the F2-isoprostane concentration in urine from 359 ± 71 pg/mg creatinine to 686 ± 139 pg/mg creatinine. In conclusion, a flat cycling stage induced changes in oxidative stress markers in erythrocytes, plasma, and urine of professional cyclists. Urine F2-isoprostane is a more useful biomarker for assessing the effects of acute exercise than the traditional malondialdehyde measurement.