Effects of boric acid supplementation on bone health in crossbred calves under tropical condition

IntroductionBoron (B) is thought to play key role in proper bone growth and development as well as have some role in regulation of minerals such as calcium (Ca), phosphorus (P) and magnesium (Mg) which act synergistically with vitamin D.ObjectivePresent study was planned in two phases to assess the effect of optimum and supranutritional levels of (B) in the form of boric acid (BA) supplementation on bone health of growing cross bred calves.MethodDuring Phase-1, twenty four male crossbred calves were blocked into four groups (n = 6) on the basis of their body weight (154.83 ± 8.5 kg), age (7–9 months) and were supplemented with 0 (C), 2.6 (T-1), 5.4 (T-2) and 10.7 (T-3) g BA for appropriate B (0.175 adjustment factor to calculate B form BA) consumption i.e. 0, 100, 200 and 400 ppm in each group respectively, for 90 days. During phase 2, twenty-one male crossbred calves were divided into 3 groups (n = 7) on the basis of their body weight (103.76 ± 4.34 kg) and age (5–8 months). All the groups were on similar dietary regimen with additional supplementation of boric acid as 0 g (control); 3.6 g (200 ppm B; T-1) and 10.8 g (600 ppm B; T-2), respectively for a period of 120 d.ResultsFrom the first experiment it is reported that plasma levels of bovine alkaline phosphatase (BALP), type I collagen cross-linked N-telopeptide (NTx) and Ca were significantly (P < 0.05) affected in T-2 and T-3 groups as compared to T-1 and control groups. Whereas, plasma osteocalcin (OCN) concentration was found to be higher in T-2 and T-3 groups as compared to control group. However, plasma concentrations (ng/mL) of tartrate resistant acid phosphatase (TRAP) remained unaltered due to dietary treatments. Based on the results, another experiment was conducted to validate the above findings and further to determine the effect of still higher i.e supranutritional levels of BA supplementation on bone health of calves. Results revealed that supplementation of BA in T-2 group had no beneficial effect on bone health as the plasma concentration of BALP, OCN, NTx, 25 (OH) vitamin D and Ca as compared to T-1 group in phase 2. Other possible attributes of bone health i.e. plasma concentration of Mg, P, parathyroid hormone (PTH), and calcitonin were not affected by BA supplementation at any levels.ConclusionOverall from present study it can be concluded that supplementation of boric acid 3.6 g/d (equivalent to 200 ppm B) in the diet of growing animals has positive effect on bone health related biomarkers (OCN, NTx and BALP) and supplementation of supranutritional level of BA i.e. 10.8 g (equivalent to 600 ppm B) level had neither additional beneficial nor harmful effect on bone health of calves.     

Effect of nonylphenol on serum testosterone levels and testicular steroidogenic enzyme activity in neonatal, pubertal, and adult rats.

Previous dose range-finding studies with nonylphenol (NP) administered to rats in a soy- and alfalfa-free diet showed apparent feminization of several endpoints in male rats at doses of 25 ppm and above. One possible mechanism contributing to these effects is a reduction of testosterone at critical developmental periods. The present study was conducted as an adjunct to a multigeneration study and was designed to examine the effect of NP on testosterone production. Male rats in the F1 and F2 generations were exposed through their dams or directly to various dietary doses of NP (0, 25, 200 and 750 ppm) throughout gestation and until sacrifice at either postnatal day 2 (PND2), PND50, or PND140. Male pups in the F3 generation were examined only on PND2. At PND2, serum testosterone levels were significantly decreased in all groups exposed to NP in the F1 generation, but not in the F2 or F3 generations. The activity of 17alpha-hydroxylase/C17, 20 lyase (P450c17) in PND2 testicular homogenates was not affected by NP treatment. In F1 and F2 PND50 and PND140 rats, NP treatment did not affect serum testosterone levels. The absolute dorsolateral prostate weight was increased in the 200 and 750 ppm dose groups only in the F1 PND50 rats, however, no significant effects were observed in other male reproductive organs. NP treatment did not affect P450c17 activity in microsomes prepared from testes of F1 PND50 or PND140 rats. However, P450c17 activity was significantly decreased in testicular microsomes of F(2) PND50 (200 and 750 ppm dose groups) and PND140 (25, 200, and 750 ppm dose groups) rats. A decrease in testicular beta-nicotinamide adenine dinucleotide phosphate (NADPH) P450 reductase was also observed in all PND50 and PND140 NP-exposed rats of the F1 and F2 generations. The ability of NP to directly inhibit P450c17 activity in vitro at concentrations of 1-100 microM was also demonstrated. These results indicate that NP can inhibit the activity of enzymes involved in testosterone synthesis, but suggest minimal effects on testosterone or testosterone-dependent endpoints via this mechanism.     

Moderate zinc deficiency negatively affects biomechanical properties of rat tibiae independently of body composition

To guide development of novel nutritional strategies aimed at reducing the incidence of stress fractures, we observed the effects of manipulating dietary zinc (Zn) content on bone integrity in Sprague–Dawley rats fed either a severely Zn-deficient (ZnD; 1 ppm), a moderately Zn-deficient (MZnD; 5 ppm) or a Zn-adequate (ZnAD; 30 ppm) diet for 6 weeks. At the completion of the diet period, body composition, bone mineral content (BMC), bone area (BA) and bone mineral density (BMD) were determined in vivo by using dual-energy X-ray absorptiometry. Following euthanasia, long bones were collected for determination of Zn content and biomechanical strength testing. Despite significant positive correlations between dietary Zn and both body weight (BW) and bone Zn content for the entire cohort (r=.77 and r=.83, respectively), rats fed MZnD or ZnAD diets did not differ in feed intakes, body composition, BMC, BA, BMD or BW. Tibial bones, but not femur bones, appear to be more responsive to dietary Zn manipulation, as all bone biomechanical strength indices in the ZnAD-fed rats were significantly greater than in rats fed the ZnD diets. Rats fed either MZnD or ZnAD diets had stronger tibiae (129% increase in maximum load and stress at maximum load, P<.01) compared with those fed ZnD diets. The load at breakage for the tibial bones of rats fed MZnD diets was not different from the ZnD rats, but lower (P<.05) than that of the ZnAD rats. These results suggest that since feed intakes, body composition, BMC, BA, BMD and BW were not significantly different between the MZnD- and ZnAD-fed animals, the reduced bone integrity observed in the MZnD-fed rats resulted from dietary Zn inadequacy, and not as a result of the reduced growth that is typically associated with Zn deficiency.     

Dietary astaxanthin inhibits colitis and colitis-associated colon carcinogenesis in mice via modulation of the inflammatory cytokines

Astaxanthin (AX) is one of the marine carotenoid pigments, which possess powerful biological antioxidant, anti-inflammatory and anti-cancer properties. The purpose of this study is to investigate possible inhibitory effect of AX against inflammation-related mouse colon carcinogenesis and dextran sulfate sodium (DSS)-induced colitis in male ICR mice. We conducted two different experiments. In the first experiment, we evaluated the effects of AX at three dose levels, 50, 100 and 200 ppm in diet, on colitis-associated colon carcinogenesis induced by azoxymethane (AOM)/DSS in mice. In the second, the effects of the AX (100 and 200 ppm) in diet on DSS-induced colitis were determined. We found that dietary AX significantly inhibited the occurrence of colonic mucosal ulcers, dysplastic crypts, and colonic adenocarcinoma at week 20. AX-feeding suppressed expression of inflammatory cytokines, including nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α and interleukin (IL)-1β, inhibited proliferation, and induced apoptosis in the colonic adenocarcinomas. Feeding with 200 ppm AX, but not 100 ppm, significantly inhibited the development of DSS-induced colitis. AX feeding (200 ppm in diet) also lowered the protein expression of NF-κB, and the mRNA expression of inflammatory cytokines, including IL-1β, IL-6, and cyclooxygenase (COX)-2. Our results suggest that the dietary AX suppresses the colitis and colitis-related colon carcinogenesis in mice, partly through inhibition of the expression of inflammatory cytokine and proliferation. Our findings suggest that AX is one of the candidates for prevention of colitis and inflammation-associated colon carcinogenesis in humans.     

The effect of diet calcium on fluoride toxicity in growing rats

The effect of dietary Ca in response to fluoride (F) treatment was investigated in rats. Rats were maintained on either adequate (0.5%) or high (2.0%) dietary Ca and given for 5 weeks, NaF in drinking water. The minimum NaF levels that inhibited body growth and reduced survival were 300 mg/L with 0.5% diet Ca and 550 mg/L with 2.0% diet Ca. With these toxic F doses, bone histology showed increased formation surfaces and thickened osteoid seams (osteoid index 6-7%). Fluoride doses 30% below toxic levels (200 and 350 mg/L for 0.5 and 2.0% diet Ca, respectively) had no demonstrable effect on bone. Additional diet Ca reduced F absorption from 76 +/- 3 to 47 +/- 3% for 0.5 and 2.0% diet Ca, respectively. Comparable absorbed doses of F produced comparable effects on bone and body growth but, with additional dietary Ca, these effects were observed with 50% lower serum and bone F levels. Variable response to NaF therapy can be produced in rats by alterations in dietary Ca alone. Results indicate that for clinical treatment the NaF dose needs to be adjusted on an individual basis but neither serum nor bone F levels can be used reliably to establish optimal doses.     

Effects of High Levels of Dietary Silicon on Bone Development of Growing Rats and Turkeys Fed Semi-purified Diets

Two experiments were conducted using a completely randomized design to study the effects of high levels of silicon (Si) supplementation on bone development, structure, and strength in growing rats and turkeys. Rats were supplemented at two dietary Si levels: 0 and 500 ppm; and the turkeys were supplemented at four dietary Si levels: 0, 135, 270, and 540 ppm in semi-purified diets of dextrose-albumin for rats and dextrose-casein for turkeys. The experiments lasted 8 and 4 weeks for the rats and turkeys, respectively. Physical, mechanical, and chemical parameters of bones were measured. All the physical and mechanical measures of bone size and strength were not different (P > 0.05) between treatments in rats and turkeys except the moment of inertia, which was lower (P < 0.01) in rats on the 500 ppm Si level of supplementation. There were small but consistent reductions in structural and strength parameters with Si supplementation which were not wholly due to differences in bodyweights of the rats and turkeys. Although bone mineral composition was not affected (P > 0.05) by Si supplementation, plasma magnesium (P = 0.08) in rats and plasma calcium (P < 0.05) in turkeys were reduced by high levels of Si supplementation. The antagonistic relations of high Si levels with calcium and magnesium were deemed to be the mechanisms through which high Si imposes its deleterious effects on bone size and strength.     

Are cadmium effects on plasma gonadotropins, prolactin, ACTH, GH and TSH levels, dose-dependent?

It is well established that cadmium affects plasma levels of the pituitary hormones studied. However, whether the effects of the metal are dose dependent needs to be clarify. This work was designed to evaluate the possible changes in plasma levels of gonadotropins, prolactin, ACTH, GH and TSH after oral cadmium exposure in adult male rats. Plasma levels of these hormones were measured in adult male rats exposed to cadmium chloride (CdCl₂) in the drinking water at the doses of 5, 10, 25, 50 or 100 ppm for one month. The lower dose of cadmium increased plasma prolactin levels and higher doses of the metal (25 or 50 ppm) decreased them. There was a continuous increase of plasma ACTH levels from the lower to 25 ppm dose of CdCl₂ and decreased them after to basal values with the highest dose. Plasma GH levels were increased with the dose of cadmium of 10 ppm, although the doses of 5, 25 and 50 ppm decreased them. Plasma LH levels were only reduced with the dose of 50 ppm of CdCl₂, whereas those of FSH increased. Plasma TSH levels were increased with the doses of 5, 25 and 100 ppm of CdCl₂. Cadmium concentration increased in pituitary with the doses of 125, 50 and 100 ppm of CdCl₂. These data suggest that cadmium differentially affects the secretory mechanisms of the pituitary hormones studied depending on the dose used. The effects of the metal on prolactin and ACTH are dose-dependent.     

The effect of variable magnesium intake on potential factors influencing endurance capacity

Rats fed a magnesium (MG) deficient diet have a lower endurance capacity than rats fed Mg adequate diets. The current study evaluates the effects of marginal, moderate, and severe Mg deficiencies on physiological and biochemical changes that may contribute to the reduced endurance capacity of Mg deficient rats. Variable levels of dietary Mg (400, 200, 100, 50 μg/g) were fed for 23 d to 5-wk-old male Osborne-Mendel rats. Indirect blood pressure and heart rate were measured during dietary treatment. Forty-eight hours after an endurance test, rats were killed and sampled for plasma glucose, insulin, and triglyceride levels. Organ weights, mineral and trace element concentrations, and carcass composition were determined. Blood pressure was lower in rats fed 50 and 100 ppm Mg during the first half of the study than in controls (400 ppm Mg). There were no significant differences in blood pressure among groups at the end of the study. Heart rate was not affected by dietary Mg intake. Plasma insulin was lowered by decreasing dietary Mg; however, plasma glucose and triglyceride concentrations were not affected by dietary Mg intake. Rats fed 100 and 50 ppm Mg diets had significantly higher calcium concentrations in plasma and gastrocnemius muscle than controls. Dietary Mg variably affected tissue trace element (iron, zinc, copper, and manganese) concentrations but did not affect Mg concentrations in any organ studied. Body composition was significantly altered by dietary Mg intake. In conclusion, variable Mg intake differentially affects the parameters evaluated. Thus, the decreased endurance capacity of the Mg deficient rat is apparently not the result of a single biochemical lesion but is likely to be multifactorial.     

Manganese toxicity in yellow birch (Betula alleghaniensis Britton) seedlings

Summary Manganese supply in nutrient solution was optimum at 5.0 ppm forBetula alleghaniensis seedlings. Growth was retarded below 0.005 ppm and above 25 ppm supply. Foliar Mn concentrations were deficient below 60 ppm, optimum at 440 ppm, and toxic above 1300 ppm. Chloroses of young leaves were associated with deficient Mn, and marginal necroses plus interveinal necrotic spots on older leaves were characteristic of toxic Mn. The results withB. alleghaniensis correspond well to those reported forB. verrucosa.     

Metabolic interactions between lead and copper in rats ingesting lead acetate

The effects of Pb ingestion with and without concurrent dietary Cu supplementation were determined on parameters associated with Cu deficiency in rats fed a nutritionally adequate diet. Groups of weanling male Sprague-Dawley rats were fed a purified (AIN-′76) diet and given Pb (0 or 500 ppm) and Cu (0, 6, or 12 ppm) as the acetate salt in deionized drinking water for 5 wk. A Pb-induced Cu deficiency resulted that was characterized by decreased levels of Cu in tissue and blood, decreased activities of the Cu-dependent enzymes, ceruloplasmin (serum) and Superoxide dismutase (erythocytes), and increased concentration of Fe in liver. These effects of Pb were prevented completely or in part by concurrent Cu supplementation. The Pb-induced decrease in hemoglobin and hematocrit values and the decrease in weight gain were not prevented by Cu supplementation of the diet and can therefore be assumed to be the direct result of a toxic effect of Pb. Although Pb ingestion resulted in decreased concentration of Cu in blood and tissue, additional dietary Cu had no effect on Pb levels.     

A comparative review of the pharmacokinetics of boric acid in rodents and humans

The pharmacokinetics of boric acid (BA) have been studied in animals and humans. Orally administered BA is readily and completely absorbed in rats, rabbits, and humans, as well as other animal species. In animals and humans, absorbed BA appears to be rapidly distributed throughout the body water via passive diffusion. Following administration of BA, the ratio of blood : soft tissue concentrations of boron (B) is approx 1.0 in rats and humans; in contrast, concentrations of B in bone exceed those in blood by a factor of approx 4 in both rats and humans. In rats, adipose tissue concentrations of B are only 20% of the levels found in blood and soft tissues; however, human data on adipose tissue levels are not available. BA does not appear to be metabolized in either animals or humans owing to the excessive energy required to break the B-O bond. BA has an affinity forcis-hydroxy groups, and it has been hypothesized to elicit its biological activity through this mechanism. The elimination kinetics of BA also appear to be similar for rodents and humans. BA is eliminated unchanged in the urine. The kinetics of elimination were evaluated in human volunteers given BA orally or intravenously; the half-life for elimination was essentially the same (approx 21 h) by either route of exposure. In rats, blood and tissue levels of B reached steady-state after 3–4 d of oral administration of BA; assuming first-order kinetics, a half-life of 14–19 h may be calculated. The lack of metabolism of BA eliminates metabolic clearance as a potential source of interspecies variation. Accordingly, in the absence of differences in metabolic clearance, renal clearance is expected to be the major determinant of interspecies variation in pharmacokinetics. Because glomerular filtration rates are slightly higher in rats than in humans, the slight difference in half-lives may be readily explained. The most sensitive toxicity end point for BA appears to be developmental toxicity in rats, with a No Observed Adverse Effect Level (NOAEL) and Lowest Observed Adverse Effect Level (LOAEL) of 55 and 76 mg BA/kg/d, respectively. Mean blood B levels in pregnant rats on gestation day 20 in the pivotal developmental toxicity study were reported to be 1.27 and 1.53 mcg B/g at the NOAEL and LOAEL, respectively. Blood B concentrations in humans are well below these levels. Average blood B levels in the most heavily exposed worker population at a borate mine was 0.24 mcg B/mL, and the estimated daily occupational exposure was equivalent to 160 mg BA/d. Blood B levels in the general population generally range from 0.03 to 0.09 mcg B/mL. These blood B values indicate an ample margin of safety for humans. In summary, the pharmacokinetics of BA in humans and rodents are remarkably similar, and interspecies differences in pharmacokinetics appear to be minimal.     

Dietary vitamin E reduces labile iron in rat tissues

Previous studies have shown that dietary vitamin E reduced generation and/or levels of superoxide. As superoxide has potential to release iron from its transport and storage proteins, and labile or available form of iron is capable of catalyzing the formation of reactive hydroxyl radicals, the effect of dietary vitamin E on labile iron pool was studied in rats. One-month-old Sprague-Dawley male and female rats were fed a basal vitamin E-deficient diet supplemented with 0, 20, 200, or 2,000 IU vitamin E/kg diet for 90 days. The levels of labile iron were measured in the liver, kidney, spleen, heart and skeletal muscle. Additionally, the levels of lipid peroxidation products were measured. The results showed that, except for labile iron in the heart of male rats, dietary vitamin E dose dependently reduced the levels of labile iron and lipid peroxidation products in all tissues of male and female rats. The findings suggest that dietary vitamin E may protect against oxidative tissue damage by reducing the generation and/or level of superoxide, which in turn attenuates the release of iron from its protein complexes.     

Aflatoxin and aflatoxicosis: V. The kinetic behaviour of dietary aflatoxins in colostrum drawn from cows postpartum

This work was conducted in order to study the kinetic behaviour of dietary aflatoxins in the colostrum of a pregnant cow exposed to contaminated feeds for a short period.In this study, two pregnant cows received a single dose of dietary aflatoxins in the form of rice powder contained 31.20 ppm aflatoxin B and 19.68 ppm aflatoxin G during the last stage of pregnancy, at about two weeks before parturition.Samples of colostrum were collected from dams and assayed for the presence of toxic metabolites as well as its conjugations by electrophoretic analysis.The results revealed that the intake of aflatoxins appeared in the colostrum pospartum as AFM₁ and also AFB_2a which is a non toxic metabolite. Moreover, it was found that the excreted metabolites including AFB_2a were conjugated to the immunoglobulin protein fraction of the colostrum.The significance of the obtained results to the newborn calf are discussed.     

Lack of mutagenic and toxic effects of low dose potassium bromate on kidneys in the Big Blue rat

Potassium bromate (KBrO3) has been classified as a genotoxic carcinogen based on positive results in the Ames test, and chromosome aberration and micronucleus tests. The purpose of the present study was to investigate the dose-response relationship for in vivo mutagenic and toxic effects of KBrO3 in the kidneys of Big Blue rats. In experiment 1, male Big Blue rats were divided into 8 groups. KBrO3 was dissolved in tap water and administered to groups 1-8 at concentrations of 0, 0.02, 0.2, 2, 8, 30, 125 and 500 ppm, respectively, for 16 weeks. Experiment 2 was performed to investigate the effects of KBrO3 at the 0.002 ppm dose approximately contained in the tap water on rat kidneys. Ten Big Blue rats were divided into 2 groups and given distilled water and tap water, respectively, for 16 weeks. In experiment 1, treatment with 500 ppm KBrO3 significantly increased the mutant and total mutation frequencies and frequency of GC to TA transversion of the lacI gene in the kidney compared to non-treatment control group, but 125 ppm and lower doses of KBrO3 had no effects. Histopathologically, renal toxic changes were observed in groups administered KBrO3 at 30 ppm or higher in a dose-dependent manner. PCNA positive cell indices in renal tubular cells were significantly increased in the kidney at doses of 125 and 500 ppm, but not at 30 ppm or lower doses, as compared to the control group. Furthermore, 8-hydroxy-2'-deoxyguanosine formation, a marker of oxidative stress, was significantly increased at 500 ppm. In experiment 2, there were no differences in any parameter between the distilled water and tap water groups. These results suggest the existence of no-effect levels for in vivo mutagenic and toxic effects, proliferation stimulus, and oxidative stress of KBrO3 in rat kidneys.     

Effect of dietary zinc and copper on peripheral blood plasma cholesterol, testosterone and histomorphology of testes in rats

Total plasma cholesterol (mg/dl) significantly (P less than 0.01) decreased from 70.8 to 54.01 as the dietary Cu levels increased from 2.5 to 5 ppm at 12 pm Zn concentrations in male weanling rats. A similar trend was observed in the blood peripheral testosterone concentration at 12 ppm Zn and 2.5 ppm Cu. Histological examination of testes revealed smaller seminiferous tubules with atrophy of germinal epithelium. Also a marked loss of spermatogenic cells was observed in Zn and Cu deficient rats.     

Interaction between nickel and copper in the rat

Two 42-d experiments were conducted with weanling male rats to study interactions between nickel and copper. In Experiment 1, a low-copper basal diet was supplemented with copper at 0 or 30 ppm and nickel at 0 or 30 ppm. Copper was added in Experiment 2 to a basal copper-deficient diet at a level of 0 or 15 ppm and nickel was supplemented at 0, 15, or 225 ppm. Responses to dietary nickel were dependent upon copper nutriture and experimental duration. Nickel had little effect on growth during the first 21 d of either study when added at low levels (15 or 30 ppm) to copper-deficient diets. Nickel supplementation depressed gains between 21 and 42 d in rats fed copper-deficient, but not copper-adequate, diets. Hematocrits and hemoglobin concentrations were not significantly affected by dietary nickel at 21 d. Nickel supplementation decreased hematocrits and hemoglobin values in copper deficient rats at 42 d in Experiment 1, but not in Experiment 2. Absorption of copper apparently was not reduced by nickel, since tissue copper concentrations were generally not decreased by increasing dietary nickel. Nickel supplementation increased lung and heart copper concentrations in Experiment 2. Liver iron was not affected by nickel, but spleen iron concentrations were reduced by nickel supplementation in copper-deficient rats in Experiment 2. The present studies suggest that nickel acts antagonistically to copper in certain biological processes.     

Dietary manganese suppresses alpha1 adrenergic receptor-mediated vascular contraction

We examined the effect of dietary manganese (Mn) on the vascular contractile machinery in rat thoracic aortas. Weanling male Sprague-Dawley rats were fed either an Mn-deficient (MnD), Mn-adequate (MnA) or Mn-supplemented (MnS) diet (<1, 10-15 and 45-50 ppm Mn, respectively). After 15 weeks on the diets the rats were sacrificed and 3-mm aortic rings were contracted in six cumulative doses of the alpha(1) adrenergic receptor agonist L-phenylephrine (l-Phe, 10(-8) to 3 x 10(-6) M) under 1.5-g preload and relaxed with one dose of acetylcholine (3 x 10(-6) M) to assess intact endothelium. The maximal force (F(max)) of contraction and relaxation, as well as the vessel sensitivity (pD(2)) were determined. Manganese deficiency, assessed by hepatic Mn content, significantly lowered the rate of animal growth. A two-way analysis of variance revealed that MnS animals developed lower F(max) when contracted with L-Phe compared with the MnD and MnA animals (P相似文献   

A study of dose response and organ susceptibility of copper toxicity in a rat model

Copper (Cu) in higher concentration is toxic and results in various organ dysfunction. We report Cu concentration in liver, brain and kidney in the rat model following chronic exposure of oral copper sulphate at different subtoxic doses and correlate the tissue Cu concentrations with respective organ dysfunction. Fifty-four male wistar rats divided in 3 groups, the control group received saline water and the experimental group (Group-IIA and IIB) received oral copper sulphate in dose of 100 and 200 mg/kg Body Weight. At the end of 30 days, 60 days and 90 days of exposure, six rats were sacrificed from each group. The maximum peak force in grip strength, latency to fall in rotarod and percentage attention score in Y-maze were significantly reduced in the copper sulphate exposed rats compared to the controls at all time points and these were more marked in Group-IIB compared to Group-IIA. Cu concentration was significantly higher in liver, kidney and brain in the Group-II compared to the Group-I. The Cu concentration was highest in the liver (29 folds) followed by kidney (3 folds) and brain (1.5 folds). Serum ALT, AST and bilirubin correlated with liver Cu, BUN with kidney Cu, and grip strength, rotarod and Y-maze findings correlated with brain Cu level. In rats, chronic oral copper sulphate exposure at subtoxic level results in neurobehavioral abnormality and liver and kidney dysfunctions due to increased Cu concentration in the respective organs. Liver is the most vulnerable organ and copper toxicity increases with increasing dose and duration of exposure.     

Assessing the effects of low boron diets on embryonic and fetal development in rodents using in vitro and in vivo model systems

To date, boron (B) essentiality has not been conclusively shown in mammals. This article summarizes the results of a series of in vitro and in vivo experiments designed to investigate the role of B in mammalian reproduction. In the first study, rat dams were fed either a low (0.04 μg B/g) or an adequate (2.00 μg B/g) B diet for 6 wk before breeding and through pregnancy; reproductive outcome was monitored on gestation day 20. Although low dietary B significantly lowered maternal blood, liver, and bone B concentrations, it had no marked effects on fetal growth or development. The goal of the second study was to assess the effects of B on the in vitro development of rat postimplantation embryos. Day 10 embryos collected from dams fed either the low or adequate B diets for at least 12 wk were cultured in serum collected from male rats exposed to one of the two dietary B treatments. Dams fed the low B diet had a significantly reduced number of implantation sites compared to dams fed the B-adequate diet. However, embryonic growth in vitro was not affected by B treatment. The aim of study 3 was to define the limits of boric acid (BA) toxicity on mouse preimplantation development in vitro. Two-cell mouse embryos were cultured in media containing graded levels of BA (from 6 to 10,000 μM). Impaired embryonic differentiation and proliferation were observed only when embryos were exposed to high levels of BA (>2000 μM), reflecting a very low level of toxicity of BA on early mouse embryonic development. Study 4 tested the effects of low (0.04 μg B/g) and adequate (2.00 μg B/g) dietary B on the in vitro development of mouse preimplantation embryos. Two-cell embryos obtained from the dams were cultured in vitro for 72 h. Maternal exposure to the low B diet for 10, 12, and 16 wk was associated with a reduction in blastocyst formation, a reduction in blastocyst cell number, and an increased number of degenerates. Collectively, these studies support the concept that B deficiency impairs early embryonic development in rodents.     

Effect of dietary vitamin E on platelet tocopherol values and 12-lipoxygenase activity

This study was designed to evaluate the effects of different amounts of dietary vitamin E on platelet tocopherol levels and 12-lipoxygenase activity when exogenous arachidonic acid was used as substrate. Weanling male Sprague-Dawley rats were fed diets containing 0, 50, and 5000 ppm of D-alpha-tocopherol acetate for 4 months. Platelet tocopherol was increased with increasing concentrations of dietary vitamin E; however, the conversion of exogenously added arachidonate by platelet to 12-HETE (12-hydroxyeicosatetraenoic acid) and thromboxane B2 from these three dietary groups was essentially the same. This study provides direct evidence that platelet 12-lipoxygenase activity is independent of its vitamin E content when exogenously added arachidonate was used as substrate.