Experimental Comparison of the Reproductive Outcomes and Early Development of the Offspring of Rats Given Five Common Types of Drinking Water

Tap water (unfiltered), filtered tap water and processed bottled water (purified water, artificial mineralized water, or natural water) are now the five most widely consumed types of drinking water in China. However, the constituents (organic chemicals and inorganic ingredients) of the five waters differ, which may cause them to have different long-term health effects on those who drink them, especially sensitive children. In order to determine which type of water among the five waters is the most beneficial regarding reproductive outcomes and the developmental behaviors of offspring, two generations of Sprague–Dawley rats were given these five waters separately, and their reproductive outcomes and the developmental behaviors of their offspring were observed and compared. The results showed that the unfiltered tap water group had the lowest values for the maternal gestation index (MGI) and offspring''s learning and memory abilities (OLMA); the lowest offspring survival rate was found in the purified water group; and the highest OLMA were found in the filtered tap water group. Thus, the best reproductive and offspring early developmental outcomes were found in the group that drank filtered tap water, which had the lowest levels of pollutants and the richest minerals. Therefore, thoroughly removing toxic contaminants and retaining the beneficial minerals in drinking water may be important for both pregnant women and children, and the best way to treat water may be with granular activated carbon and ion exchange by copper zinc alloy.     

3,5,3'-Triiodothyronine administered to rat dams during lactation increases milk yield and triglyceride concentration and hastens pups growth

It is known that lactation induces a mild hypothyroid state in rats and other mammals while thyroid hormone administration increases milk secretion in ruminants. The aim of this study was to investigate the effects of a moderate dose of 3,5,3'-triiodothyronine (T3), administered to rat dams during lactation on pups' growth and milk yield and composition. Primiparous Wistar rats with litters adjusted to 10 pups per dam received either tap water or T3 (75 microg/kg x day) in their drinking water from parturition till weaning. Food and water intake of dams and body weight of dams and pups were measured daily. In other groups of rats with similar treatments, milk yield of dams, macronutrient milk composition, and mammary arteriovenous differences for triglycerides (TG) and glucose were also determined. Dams treated with T3 ingested more food and their pups gained more weight than controls. Milk yield, milk TG concentration and glucose extraction by mammary glands were also higher in T3 treated dams. The results show that compensation of the mild hypothyroidism of the lactating rat may contribute to an increase in milk production and lipid levels, leading to an increase in growth of pups.     

Estimation of absorbed cadmium in tissues of male and female albino rats through different routes of administration

The resultant effects of cadmium exposure are seen in almost all the systems of the body, however, this study is designed to quantify its accumulation in tissues of animals exposed to cadmium. The rats were divided into two distinct groups of males and females, which were then divided into three groups, each for the monitoring of exposure. Group 1 served as control male and female and received normal rat chow and tap water. Group 2 males and females were treated with 5 mg/kg body weight of cadmium chloride (Cd) intraperitoneally for eight days while Group 3 males and females rats received 100 ppm of Cd in drinking water for 18 days. The concentrations of cadmium were analyzed in tissues (lung, stomach, kidney, heart, spleen, blood) by AAS. There were significant (P.     

Multi-Generational Drinking of Bottled Low Mineral Water Impairs Bone Quality in Female Rats

Background

Because of reproductions and hormone changes, females are more sensitive to bone mineral loss during their lifetime. Bottled water has become more popular in recent years, and a large number of products are low mineral water. However, research on the effects of drinking bottled low mineral water on bone health is sparse.

Objective

To elucidate the skeletal effects of multi-generational bottled water drinking in female rats.

Methods

Rats continuously drank tap water (TW), bottled natural water (bNW), bottled mineralized water (bMW), or bottled purified water (bPW) for three generations.

Results

The maximum deflection, elastic deflection, and ultimate strain of the femoral diaphysis in the bNW, bMW, and bPW groups and the fracture strain in the bNW and bMW groups were significantly decreased. The tibiae calcium levels in both the bNW and bPW groups were significantly lower than that in the TW group. The tibiae and teeth magnesium levels in both the bNW and bPW groups were significantly lower than those in the TW group. The collagen turnover markers PICP (in both bNW and bPW groups) were significantly lower than that in the TW group. In all three low mineral water groups, the 1,25-dihydroxy-vitamin D levels were significantly lower than those in the TW group.

Conclusion

Long-term drinking of low mineral water may disturb bone metabolism and biochemical properties and therefore weaken biomechanical bone properties in females. Drinking tap water, which contains adequate minerals, was found to be better for bone health. To our knowledge, this is the first report on drinking bottled low mineral water and female bone quality on three generation model.     

Experimental hypothyroidism inhibits delta-aminolevulinate dehydratase activity in neonatal rat blood and liver

The aim of this study was to investigate the potential relationship between hypothyroidism and delta-aminolevulinate dehydratase (delta-ALA-D) activity in rat blood and liver. Experimental hypothyroidism was induced in weanling rats by exposing their mothers to propylthiouracil (PTU) diluted in tap water (0.05% w/ v), ad libitum, during the lactational period (PTU group). Control (euthyroid) group included weanling rats whose mothers received just tap water, ad libitum, during the lactational period. Reverted-hypothyroid group (PTU + 3,3',5-triiodo-L-thyronine [T(3)]) included weanling rats whose mothers were exposed to PTU similarly to those in the hypothyroid group, but pups received daily subcutaneous injections of T(3) (20 microg/kg, from Postnatal Days 2-20). After the treatment, serum T(3) levels were drastically decreased (around 70%) in the PTU group, and this phenomenon was almost reverted by exogenous T(3). PTU decreased blood delta-ALA-D activity by 75%, and T(3) treatment prevented such phenomena. Erythrocytes and hemoglobin levels were increased by 10% in PTU-treated animals and higher increments (around 25%) were observed in these parameters when exogenous T(3) was coadministered. Dithiothreitol did not change blood delta-ALA-D activity of PTU-exposed animals when present in the reaction medium, suggesting no involvement of the enzyme's essential thiol groups in PTU-induced delta-ALA-D inhibition. PTU did not affect blood delta-ALA-D activity in vitro. These results are the first to show a correlation between hypothyroidism and decreased delta-ALA-D activity and point to this enzyme as a potential molecule involved with hypothyroidism-related hematological changes.     

Suckling ability and maternal prolactin levels in hypothyroid rats

Long-Evans rats and their offspring were made hypothyroid by addition of the antithyroid goitrogen 6-N-propylthiouracil (PTU) to the drinking water (0.1%) from the day of parturition. Serum concentrations of prolactin (PRL), thyroid-stimulating hormone (TSH) and thyroxine (T4) were determined by double radioimmunoassay (RIA). From the fifth postnatal day, body weight of PTU-treated pups was significantly lower than that of control rats, and a strikingly elevated serum TSH level and nondetectable amount of T4 were measured both in PTU-exposed mothers and their offspring at Day 10 postpartum. To test the youngs' suckling capability and the amount of maternal milk production, 10- and 15-day-old normal and PTU-treated pups were separated from their mothers for 4 hr in the morning and then reunited and allowed to suckle. Normal pups gained body weight at the end of both the first and second hour postreunion, while PTU pups gained only during the first hour and lost weight in the second hour of testing. When the pups were exchanged between normal and PTU mothers, opposite results were obtained, indicating that the reduced gain in hypothyroid rats was not due to impaired suckling capability, or insufficient sensory stimulation for milk secretion but to a decreased milk production of PTU mothers. In accordance with this, in lactating hypothyroid rats both the basal (presuckling) level and the suckling-induced rise of serum PRL were found significantly depressed.     

Oxidative stress induced by gibberellic acid on kidney tissue of female rats and their progeny: biochemical and histopathological studies

Gibberellic acid (GA₃) is an endogenous plant growth regulator used worldwide in agriculture. The objective of this study was to investigate the effects of GA₃ on the kidney function of adult rats and their pups. Female Wistar rats were given daily 200 ppm GA₃ in drinking water from the 14th day of pregnancy until day 14 after delivery. GA₃ induced nephrotoxicity, as evidenced by a reduction in the 24-h urine volume and an increase in plasma creatinine, urea and uric acid levels. Nephrotoxicity was objectified by a significant increase of malondialdehyde level and a decrease of antioxidant enzyme activities like catalase, superoxide dismutase, glutathione peroxidase and glutathione content in kidneys of suckling pups and their mothers. Kidney histological studies confirmed biochemical parameters. We concluded that the exposure of rats to GA₃ induced oxidative stress and histopathological changes in kidneys of suckling rats and their mothers during late pregnancy and early postnatal periods.     

Interaction of lead with some essential elements in rat’s kidney in relation to age

The aim of this study was to evaluate the interaction of lead given orally with Fe, Zn, and Cu in adult female rats and in their pups. Kidney was chosen for studying this interaction. Four different doses of lead (acetate) from 1500 to 7500 ppm were administered to mature female albino rats in beverages during 6 wk. The exposure lasted from mating up to 3 wk after delivery. Pb, Fe, Zn, and Cu were determined in kidneys of mothers and pups. Histopathological examinations were also performed. Results showed significantly lower concentrations of Fe, Zn, and Cu in kidneys of mothers on all lead levels. Their pups showed no change in concentrations of essential elements and even increased Fe at the highest exposure level. Concentrations of Pb and histopathological changes in the kidney were similar in mothers and offspring, although pups received only a fraction of the mothers’ doses. Our results indicate that in immature animals the interaction of Pb with essential elements in the kidney is different from that in their mothers.     

TRACE METALS AND METHYL MERCURY: ASSOCIATIONS AND TRANSFER IN HARP SEAL (PHOCA GROENLANDICA) MOTHERS AND THEIR PUPS

Milk samples from the stomachs of harp seal pups were analysed for Cu, Zn, Se, Cd and Hg, as were liver, kidney, and muscle from mother-pup pairs. Tissues were also analysed for MeHg. Milk contained, in addition to essential trace metals, Cd and Hg (57 ng/g and 6.5 ng/g respectively).
Pups had mercury in all three tissues. The percent methyl mercury in liver of pups was higher than in liver of mothers. Mercury in muscle was mostly methyl mercury in both mothers and pups. Total mercury in liver of mothers but not pups was correlated positively with selenium. Estimates of ingested mercury by pups indicated they had acquired most of their mercury during gestation.
Although mothers had cadmium in liver and kidney, it was not detected in tissues of pups. Cadmium did not transfer across the placenta, while mercury did. Tissue concentrations of Cu and Zn were higher in pups than mothers. The presence of metallothionein in pup tissues was postulated.
A strong positive correlation of copper and selenium between mothers and pups indicated transfer of these elements from mother to pup in direct proportion to their concentrations in maternal liver and kidney.     

Microbial manipulation of the rat dam changes bacterial colonization and alters properties of the gut in her offspring

The impact of an altered bacterial colonization on gut development has not been thoroughly studied, despite the increased risk of certain diseases with a disturbed microbiota after birth. This study was conducted to determine the effect of microbial manipulation, i.e., antibiotic treatment or Escherichia coli exposure, of the dam on bacterial colonization and gut development in the offspring. Pregnant rats were administered either broad-spectrum antibiotics 3 days before parturition or live nonpathogenic E. coli Culture Collection of University of G?teborg, Sweden type strain (CCUG 29300(T)) 1 wk before parturition and up to 14 days of lactation in the drinking water. Cecal bacterial levels, gut growth, intestinal permeability, digestive enzyme levels, and intestinal inflammation were studied in 2-wk-old rats. Pups from dams that were antibiotic-treated had higher densities of Enterobacteriaceae, which correlated with a decreased stomach growth and function, lower pancreatic protein levels, higher intestinal permeability, and increased plasma levels of the acute phase protein, haptoglobin, compared with pups from untreated mothers. Exposure of pregnant/lactating mothers to E. coli CCUG 29300(T), also resulting in increased Enterobacteriaceae levels, gave in the offspring similar results on the stomach and an increased small intestinal growth compared with the control pups. Furthermore, E. coli pups showed increased mucosal disaccharidase activities, increased liver, spleen, and adrenal weights, as well as increased plasma concentrations of haptoglobin. These findings indicate that disturbing the normal bacterial colonization after birth, by increasing the densities of cecal Enterobacteriaceae, appears to have lasting effects on the postnatal microflora, which affects gut growth and function.     

Neuroprotective activity of cannabinoid receptor‐2 against oxidative stress and apoptosis in rat pups having experimentally‐induced congenital hypothyroidism

In this study, it was aimed to show the cannabinoid receptor‐2 (CB2) role, which is a part of neuroprotective endocannabinoidal system, against increasing nitric oxide synthetase (iNOS, eNOS) levels and the apoptotic activity (caspase‐3, caspase‐9, and DNA in situ fragmentation) within the postnatal critical period in pups of pregnant rats with artificially induced maternal thyroid hormone (TH) deficiency. Each of the three groups established comprised one male and two female rats, and they were coupled. Their pups were used. In the first two groups, the mothers were treated with 0.025% MMI during the critical period of the pregnancy. In the third group, as the control group, the mothers and pups were not treated. Euthanasia was applied to the pups in Group I on Day 10, and to the pups in Groups II and III on Day 21. In the biochemical analyses, total T4 levels of both mothers and pups in Group I and II were found to be lower than those of the control group. Histopathologically, karyopyknosis in migrating neurons and demyelinization were observed in both groups. Caspase‐3 and −9 expressions and TUNEL reactions showed parallelism to these findings. eNOS and iNOS activities were also increased in Groups I and II. CB2 receptor activity was observed in the fore and mid brain in Group I, and in the whole brain in Group II. In conclusion, apoptosis was triggered via oxidative stress in hypothyroid pups. Accordingly, neuroprotective activity of CB2 receptors were motivated spontaneously to resist to CNS lesions during the first 3 weeks of postnatal period. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1334–1347, 2017     

Effects of chronic ingestion of caffeine on mammary growth and reproduction in mice

Normal mammary gland growth and reproduction were examined in C3H/HeMei mice given caffeine as drinking water (500 mg/l tap water) after weaning on day 20 of age. Caffeine ingestion had little effects on any of the day of vaginal opening, body growth, pattern of estrous cycles, mammary gland growth and reproduction except for the rearing rate on day 12 of lactation. Five out of 12 mothers given caffeine lost all pups before day 12 and resulted in 51% of the rearing rate on that day, while that of the control was 91%. The rate did not change thereafter in either group. The results indicate that the chronic heavy ingestion of caffeine would induce the high mortality of pups during early stage of lactation.     

Effects of iodine repletion on thyroid morphology in iodine and/or selenium deficient rat term fetuses, pups and mothers.

It has been suggested that selenium deficiency aggravates the iodine-induced thyroid inflammation and necrosis in iodine-deficient Wistar rats and possibly in man. Studies were carried out to determine whether large amounts of iodine given to iodine-deficient pregnant Sprague-Dawley rats with or without selenium deficiency would induce inflammation and necrosis in their term fetal thyroids. Iodine deficiency was induced in the dams by a low iodine diet or perchlorate in the drinking water and iodine excess was achieved by iodinated drinking water during pregnancy or daily subcutaneous injections of iodine from days 20 to 22 of pregnancy, 1 day after perchlorate was discontinued. Studies were also carried out in 30-day-old pups whose nursing mothers were iodine-deficient (perchlorate) with or without selenium deficiency from conception onward. The administration of iodine restored the morphologic changes in the thyroid induced by iodine deficiency, irrespective of selenium status, toward normal without inflammatory changes or necrosis. Possible explanations for these unexpected findings are discussed.     

Cadmium,iron and zinc interaction and hematological parameters in rat dams and their offspring

The effects of cadmium (Cd) were evaluated in offspring exposed from birth until weaning (neonatal day 0–21) and 4 weeks after exposure cessation focusing on iron (Fe) and zinc (Zn) levels in organs and hematological parameters. Wistar female rats were administered 50 mg Cd/L in drinking water (Cd-exposed) for 4 weeks before mating and during 3 weeks of gestation plus 3 weeks of lactation. Controls were supplied drinking water. At birth, part of Cd-exposed dams’ litters was cross-fostered to control dams (CCd group) and their control litters were cross-fostered to Cd-exposed dams (CdC group). This procedure enabled to discern the effects of gestational, lactational and gestational plus lactational Cd exposure until weaning in F₁ offspring. Elements were analyzed by atomic absorption spectrometry; hematological parameters manually; and histopathological changes by light microscopy. Gestational plus lactational exposure in Cd-exposed dams and their offspring increased Cd and decreased Fe levels, increased Zn in dams and decreased Zn and body weights in 11- and 21-day pups. In 21-day weanling pups, decreased red blood cell (RBC) count, hemoglobin and hematocrit values and increased reticulocytes in peripheral blood were also found with concomitant histopathological finding of extramedullary hematopoiesis in the liver. In cross-fostered pups with gestational exposure (CCd pups), Fe in the liver decreased on day 11 and Zn increased in the kidney on day 21 whereas in pups with lactational exposure (CdC pups) Zn in the brain decreased on day 11 and Fe decreased in the liver and brain on day 21. Regardless of exposure cessation at weaning, in offspring with gestational plus lactational exposure (Cd-exposed) body weights, kidney and brain Fe levels and RBC and hemoglobin remained decreased in blood until puberty. Furthermore Zn levels increased in the liver, kidney and brain. It was concluded that gestational plus lactational Cd exposure caused decreases in Fe and Zn levels and hematotoxic effects in F₁ offspring more pronouncedly than exposure during either gestational or lactational period alone and the adverse effects of maternally mediated Cd exposure continued after exposure cessation into adulthood.     

Ascorbic Acid Attenuates Lead-Induced Alterations in the Synapses in the Developing Rat Cerebellum

Biological Trace Element Research - We evaluated the effect of lead (Pb) and ascorbic acid treatment of pregnant female rats on cerebellar development in pups. Pb was administered in drinking water...     

Evalution of toxicity of abcisic acid and gibberellic acid in rats: 50 days drinking water study

In the present study, the influence of subchronic effects of two plant growth regulators (PGRs) [Abcisic acid (ABA) and Gibberellic acid (GA3)] on antioxidant defense systems [reduced glutathione (GSH), glutathione reductase (GR), superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT)] and lipid peroxidation level (malondialdehyde = MDA) in various tissues of the rat were investigated during treatment as a drinking water model. 75 ppm of ABA and GA3 in drinking water were continuously administered orally to rats (Sprague-Dawley albino) ad libitum for 50 days. The PGRs treatments caused different effects on the antioxidant defense systems and MDA content of dosed rats compared to controls. The lipid peroxidation end product MDA significantly increased in the lungs, heart and kidney of rats treated with GA3 without significant change in the spleen. ABA caused also a significant increase in MDA content in the spleen, lungs, heart and kidney. The GSH levels were significantly depleted in the spleen, lungs and stomach of rats treated with ABA without any change in the tissues of rats treated with GA3 except the kidney where it increased. Antioxidant enzyme activities such as SOD significantly increased in the lungs and stomach and decreased in the spleen and heart tissues of rats treated with GA3. Meanwhile, SOD significantly decreased in the spleen, heart and kidney and increased in the lungs of rats treated with ABA. While CAT activity significantly decreased in the lungs of rats treated with GA3, a significant increase occurred in the heart of rats treated with both PGRs. On the other hand, the ancillary enzyme GR activity in the tissues were either significantly depleted or not changed with PGRs treatment. The drug metabolizing enzyme GST activity significantly decreased in the lungs of rats treated with ABA but increased in the stomach of rats treated with both PGRs. As a conclusion, the rats resisted oxidative stress via the antioxidant mechanism. But the antioxidant mechanism could not prevent the increases in lipid peroxidation in rat's tissues. This data, along with changes, suggests that PGRs produced substantial systemic organ toxicity in the spleen, lungs, stomach, heart and kidney during a 50-day period of subchronic exposure.     

Effect of chronic fluorosis on lipid peroxidation and histology of kidney tissues in first- and second-generation rats

This experiment was designed to investigate the lipid peroxidation and histological effects of chronic fluorosis on first- and second-generation rat kidney tissues. Sixteen virgin female Wistar rats were mated with eight males (2∶1) for approx 12 h to obtain first-generation rats. Mating was confirmed by the presence of sperm in vaginal smears. Sperm in vaginal smears was observed in 10 of 16 rats (d 0). These rats were identified as pregnant and included in this experiment. Pregnant rats were divided into two experimental groups (control and fluoride-supplemented), each containing five rats. The pregnant rats in the fluoride-supplemented group were exposed to 30 mg/L sodium fluoride (NaF) in commercial drinking water containing 0.07 mg/L NaF throughout the gestation and the lactation periods. After the lactation period, young animals (first generation [F1]) were exposed to the same amount of NaF in drinking water for 4 mo. At the end of the 4-mo experimental period, nine randomly chosen male rats (F1) were sacrificed, and the kidneys were removed for the histological and lipid peroxidation examinations. The remaining eight female rats were mated with four males (2∶1) for approx 12 h to obtain second-generation rats. Six female were identified as pregnant, and treated similarly throughout the gestation and the lactation periods. After the lactation period, the young male rats (second-generation male rats [F2]) were also treated similarly for 4 mo. At the end of the 4-mo experimental period, nine randomly chosen male rats (F2) were sacrificed, and the kidneys were removed for the histological and lipid peroxidation examinations. The rats in the control groups underwent the same procedure without NaF supplementation. It was found that the plasma fluoride and kidney TBARS levels of fluoride-supplemented F1 and F2 rats were higher than controls. Hydropic epithelial cell degenerations and moderate tubular dilatation were observed in some proximal and distal tubules. There were markedly focal mononuclear cell infiltrations and hemorrhage at some areas of the interstitium, especially at the corticomedullar junction. Mononuclear cell infiltrations were also evident in some peritubular and perivascular areas. Most of the vascular structures were congestive. Many Bowman capsules were narrowed. The severe degenerative changes in most of the shrunken glomerules and vascular congestion were also observed. It is concluded that chronic fluorosis causes a marked destruction in kidney tissues of F1 and F2 rats by causing lipid peroxidation. Department of Orthopedics, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey     

Ganglioside alterations in various brain areas, liver and kidney from chronic alcoholic rats

Ethanol was administered to Wistar male rats for 4 or 10 months and to female rats for 2 months (including gestation), using a 20% ethanol-water solution as the only fluid. Gangliosides (expressed as NeuAc) from forebrain, cerebellum, brain stem, liver and kidney of the alcoholic rats and their newborns were determined by densitometry. Forebrain and liver from males showed a statistically significant increase in their ganglioside-NeuAc content after 4 months of alcohol ingestion. In addition, when the treatment lasted up to 10 months the increase was larger. In contrast, a significant decrease of cerebellar and kidney ganglioside-NeuAc content was found after 10 months. The ganglioside pattern of the different sources displayed a variable profile. Moreover, while alcohol fed mothers showed a significant increase in the ganglioside-NeuAc content of cerebellum and liver, and a decrease in the brain stem, newborns of mothers given alcohol in their drinking water exhibited an increase of ganglioside-NeuAc content in cerebellum, liver and kidney and a decrease in forebrain.