Lactating and nonlactating rats differ to renal toxicity induced by mercuric chloride: the preventive effect of zinc chloride.

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.

Distinct response of lactating and nonlactating rats exposed to inorganic mercury on hepatic δ-aminolevulinic acid dehydratase activity.

This study investigated if lactating and nonlactating rats presented differences in relation to hepatic sensitivity to HgCl2 and the potential preventive role of ZnCl2. Lactating (days 3-12 of lactation) and nonlactating rats received 27 mg/kg ZnCl2 for five consecutive days and 5 mg/kg HgCl2 for five subsequent days. Lactating and nonlactating rats exposed to HgCl2 presented a decrease in food intake, a decrease in plasma alanine aminotransferase (ALT), and an increase in hepatic Hg levels when compared to the control group. Only lactating rats exposed to HgCl2 presented an increase in hepatic δ-aminolevulinic acid dehydratase activity. On the other hand, only nonlactating rats exposed to HgCl2 presented an increase in plasma aspartate aminotransferase (AST). ZnCl2 pre-exposure partially protected the increase in plasma AST activity presented by nonlactating rats and potentiated the liver Hg accumulation in lactating rats. Pups from the Sal-Hg and Zn-Hg groups showed a decrease in absolute liver weight and an increase in liver Hg levels. Summarizing, this study demonstrated that lactating rats presented distinct biochemical responses compared to nonlactating rats exposed to HgCl2 when hepatic parameters were evaluated.

Repeated administration of diphenyl diselenide to pregnant rats induces adverse effects on embryonic/fetal development.

The present study was carried out to investigate the effects of diphenyl diselenide, (PhSe)(2), on embryo-fetal development. Dams were treated subcutaneously with 1.5, 3.0 and 6.0 mg/kg (PhSe)(2) from days 6 to 15 of pregnancy. After cesarean section at gestation day (GD) 20, external and skeletal abnormalities were evaluated. A decrease in maternal body weight gain was found in (PhSe)(2) groups, indicating maternal toxicity. There was a reduction in the fetal weight and in crown-rump (CR) length of fetuses at three doses tested. The occipito-nasal length decreased in fetuses from dams exposed to 3.0 mg/kg (PhSe)(2). Signs of delayed ossification in the skull, sternebrae and limbs were observed in all (PhSe)(2) groups, revealing a relation between morphological alterations and growth retardation in fetuses, but none of the changes appeared to be dose-dependent. Exposure of dams to (PhSe)(2) resulted in altered placental morphology that may have contributed to adverse reproductive outcomes. We concluded that (PhSe)(2) is toxic to dams and induces developmental delay of the fetal skeleton, but does not cause externally visible malformations in rat fetuses, in this experimental procedure.

Diphenyl diselenide changes behavior in female pups.

Diphenyl diselenide, (PhSe)(2), is an organoselenium compound that affects a number of neuronal processes. The effect of maternal subcutaneous (s.c.) injection of 25 mg/kg (PhSe)(2) once daily during early postnatal development (from PND 1 to 21) was evaluated in offspring of Wistar rats. The physical and neural reflexes were recorded at pre-weaning period. The behavioral changes in the elevated plus-maze (EPM), open-field and rotarod tasks were performed in 28-day-old pups. Selenium brain status was significantly increased ( approximately 41%) in rat pups. Statistically significant decreases in body weight were observed during lactation period in male and female pups exposed to 25 mg/kg (PhSe)(2). There were no dose-related changes on landmarks indicative of physical and reflexologic parameters of development in rats. (PhSe)(2) induced a disinhibitory effect in EPM behavior according to gender. Specifically, exposure to (PhSe)(2) increased entries and duration in the open arms of the EPM in females but not in males. Locomotor activity and rearing increased by (PhSe)(2) exposure in both male and female offspring in the open field. Both groups were similar in response to motor coordination in the rotarod. We concluded that maternal (PhSe)(2) exposure during lactation increased selenium levels in the pup brain and caused changes on developmental and behavioral parameters of Wistar rat offspring.

Exposure of mothers to diphenyl ditelluride during the suckling period changes behavioral tendencies in their offspring.

The long-lasting possible influence of maternal exposure to 0.03 mg/kg of diphenyl ditelluride during the first 14 days of lactational period on later offspring behavior was examined in Wistar rats. Open-field locomotor activity, spontaneous alternation in the T-maze, behavior in the elevated plus-maze, motor coordination in the coat-hanger and rotorod tasks were evaluated in 30 day old pups. There were no significant specific overt signs of maternal intoxication. There were a small (less than 5%) but significant transitory differences in the body weight gain of pups between exposed and control groups, which were apparent from day 30 of suckling. Locomotor activity in the open-field task was similar between telluride and control groups. In the coat-hanger test, the latency before falling for the tellurium group was higher than that of the control group. However, the behavior of both groups was similar in the rotorod test and spontaneous alternation in the T-maze. Tellurium-treated pups presented a higher number of entries and spent more time in the open arms of the elevated plus-maze than control pups. The behavioral alterations observed here after tellurium exposure can be cautiously interpreted as an indication of behavioral disinhibition. In conclusion, this study demonstrated that dam exposure to diphenyl ditelluride can cause subtle behavioral changes in the offspring, which can be related to neurotoxic effects of diphenyl ditelluride.

Sub-chronic administration of diphenyl diselenide potentiates cadmium-induced testicular damage in mice.

Sub-chronic cadmium (Cd) exposure causes testicular damage in mice. The mode of action may involve oxidative stress and especially lipid peroxidation. The present study has monitored the pathogenesis of testicular damage during sub-chronic Cd exposure and has evaluated the potential protective effect of antioxidant therapy with diphenyl diselenide (PhSe)(2). Male mice were dosed with 2.5 mg/kg CdCl(2) (2.5 mg/kg) with or without (PhSe)(2) (5 micromol/kg) at 30 min post-exposure using a model of five weekly subcutaneous injections. Histological evaluation of the testis was performed across a 4 week test period. Animals exposed to CdCl(2) and CdCl(2) plus (PhSe)(2) displayed a reduction in body weight gain and testicular weight. Progressive damage and histolopathological changes in the testis were not remedied with, but rather were potentiated by, (PhSe)(2) therapy. We conclude that (PhSe)(2) enhances testicular injury in an animal model for sub-chronic Cd exposure mice.

Teratogenic effects of diphenyl diselenide in Wistar rats.

Diphenyl diselenide is an organoselenium compound with potential therapeutic use. The present study evaluates the effects of single maternal subcutaneous injection of 50 and 100mg/kg diphenyl diselenide [(PhSe)2] at gestational days (GD) 6, 10 or 17 in Wistar rats. The highest dose of (PhSe2 was also administered at GD 7-12. External and internal fetal soft-tissue examination was performed at GD 20. No mortality was observed in fetuses or dams at any (PhSe)2 treatment group. Neither did exposure to (PhSe)2 cause significant changes to fetal body weight, organ weight, or fetal size when administered at GD 6-8, 10-12 or 17. Exposure to 100mg/kg (PhSe)2 at GD 9 produced significant changes in fetal biometry (crown-rump (CR) length) and body weight. No significant increase in the proportion of fetuses with external visible abnormalities was observed in groups exposed to (PhSe)2. Skeletal anomalies were observed in fetuses in the GD 9-11 treatment groups and included incomplete ossification of cranial bones, misshapen and incomplete ossification of sternebrae, reduced sternebrae number, wavy and extra ribs, incomplete ossification of fore and hindpaw bones and incomplete ossification of sacral and caudal bones. We conclude that maternal administration of (PhSe)2 during GD 7-12 led to increased incidences of these skeletal variations or anomalies, but did not cause externally visible malformations in rat fetuses.

Diphenyl diselenide reverses cadmium-induced oxidative damage on mice tissues.

The concept that selenium-containing molecules may be better antioxidants than classical antioxidants, has led to the design of synthetic organoselenium compounds. In the present investigation subchronic deleterious effects of cadmium-intoxication in mice and a possible protective effect of diphenyl diselenide (PhSe)2 (5 micromol/kg) were studied. Male adult Swiss albino mice (25-35 g) received CdCl2 (10 micromol/kg, subcutaneously), five times/week, for 4 weeks. A number of toxicological parameters in blood, liver, kidney, spleen and brain of mice were examined including delta-aminolevulinic acid dehydratase (delta-ALA-D) activity, lipid peroxidation and ascorbic acid content, the parameters that indicate tissue damage such as plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, creatinine and lactate dehydrogenase (LDH) were also determined. The results demonstrated that cadmium caused inhibition of delta-ALA-D activity in liver (24%), kidney (33%) and spleen (73%) and (PhSe)2 therapy was effective in restoring enzyme activity in all tissues. A reduction in ascorbic acid content was observed in kidney (11%) and spleen (10.7%) of cadmium-treated mice and (PhSe)2 was only effective in improving this reduction in kidney. An increase of lipid peroxidation induced by cadmium was noted in liver (29%) and brain (28%) tissues and (PhSe)2 therapy was effective in restoring TBARS levels in both tissues. We also observed an increase on plasma LDH (1.99-times), AST (1.93-times) and ALT (4.24-times) activities. (PhSe)2 therapy was effective in restoring AST activity at control level. (PhSe)2 did not present toxic effects when plasma parameters were evaluated. The results suggest that the administration of an antioxidant (PhSe)2, during cadmium intoxication may provide beneficial effects by reducing oxidative stress in tissues.