The effect of calcium on lead absorption in rats.
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ABSTRACT:
SUBMITTER: Meredith PA
PROVIDER: S-EPMC1165037 | biostudies-other | 1977 Sep
REPOSITORIES: biostudies-other
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Project description:Lead is a naturally-occurring element. It has been known to man for a long time, and it is one of the longest established poisons. The current consensus is that no level of lead exposure should be deemed "safe". New evidence regarding the blood levels at which morbidities occur has prompted the CDC to reduce the screening guideline of 10??g/dl to 2??g/dl. Measurable cognitive decline (reduced IQ, academic deficits) have been found to occur at levels below 10??g/dl, especially in children. Knowledge of lead pharmacology allows us to better understand its absorption and metabolization, mechanisms that produce its medical consequences. Based upon an original and very simplified compartmental model of Rabinowitz (1973) with only three major compartments (blood, bone and soft tissue), extensive biophysical models sprouted over the following two decades. However, none of these models have been specifically designed to use new knowledge of lead molecular dynamics to understand its deleterious effects on the brain. We build and analyze a compartmental model of lead pharmacokinetics, focused specifically on addressing neurotoxicity. We use traditional phase space methods, parameter sensitivity analysis and bifurcation theory to study the transitions in the system's behavior in response to various physiological parameters. We conclude that modeling the complex interaction of lead and calcium along their dynamic trajectory may successfully explain counter-intuitive effects on systemic function and neural behavior which could not be addressed by existing linear models. Our results encourage further efforts towards using nonlinear phenomenology in conjunction with empirically driven system parameters, to obtain a biophysical model able to provide clinical assessments and predictions.
| S-EPMC6775169 | biostudies-literature
Project description:In our current investigation, we evaluated the effect of Chlorella pyrenoidosa protein hydrolysate (CPPH) and Chlorella pyrenoidosa protein hydrolysate-calcium chelate (CPPH-Ca) on calcium absorption and gut microbiota composition, as well as their in vivo regulatory mechanism in SD rats fed low-calcium diets. Potent major compounds in CPPH were characterized by HPLC-MS/MS, and the calcium-binding mechanism was investigated through ultraviolet and infrared spectroscopy. Using high-throughput next-generation 16S rRNA gene sequencing, we analyzed the composition of gut microbiota in rats. Our study showed that HCPPH-Ca increased the levels of body weight gain, serum Ca, bone activity, bone mineral density (BMD) and bone mineral content (BMC), while decreased serum alkaline phosphatase (ALP) and inhibited the morphological changes of bone. HCPPH-Ca up-regulated the gene expressions of transient receptor potential cation V5 (TRPV5), TRPV6, calcium-binding protein-D9k (CaBP-D9k) and a calcium pump (plasma membrane Ca-ATPase, PMCA1b). It also improved the abundances of Firmicutes and Lactobacillus. Bifidobacterium and Sutterella were both positively correlated with calcium absorption. Collectively, these findings illustrate the potential of HCPPH-Ca as an effective calcium supplement.
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Project description:ContextVitamin D is often recommended for use with calcium supplements to increase absorption. There are no systematic studies of vitamin D on calcium absorption that indicate what dose should be recommended.ObjectiveOur objective was to study the effect of increasing doses of vitamin D3 on calcium absorption.Design and settingWe conducted a randomized double-blind placebo-controlled trial at Creighton University Medical Center, Omaha, NE.ParticipantsParticipants included 163 postmenopausal Caucasian women with vitamin D insufficiency, defined as a serum 25-hydroxyvitamin D (25OHD) below 20 ng/ml (50 nmol/liter).InterventionParticipants were randomized to receive one of the vitamin D3 doses, 400, 800, 1600, 2400, 3200, 4000, or 4800 IU/d, or placebo for 1 yr. Calcium intake was increased to 1200-1400 mg daily by giving daily calcium citrate.Main outcomeWe evaluated the change in calcium absorption on vitamin D.ResultsMean serum 25OHD increased from baseline 15.6 ng/ml (39 nmol/liter) to 46.5 ng/ml (112 nmol/liter) in subjects randomized to the highest dose of vitamin D (4800 IU). Calcium absorption was more significantly related to serum 25OHD (R2=0.50; P=0.001) than dose (R2=0.47; P=0.033). Calcium absorption of a 100-mg dose increased from 52-58% (6 mg) over a serum 25OHD range of 20-66 ng/ml (50-165 nmol/liter).ConclusionsThere was no evidence of a threshold for reduced calcium absorption in the serum 25OHD range of 10-66 ng/ml (25-165 nmol/liter). The increase in absorbed calcium of 6% on high doses of vitamin D is so small that the same amount could be obtained from half a glass of milk (100 ml) or 100 mg elemental calcium. The results challenge assumptions about the value of adding vitamin D to increase calcium absorption except when serum 25OHD is very low that is less than 10 ng/ml (25 nmol/liter).
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Project description:ScopeBlueberries are rich sources of bioactive polyphenols that may provide health benefits when consumed regularly, leading to their increased marketing as dietary supplements. However, the metabolic changes associated with consuming concentrated doses of purified polyphenols, as may be present in dietary supplements, are unknown, especially when considering the colonic metabolites formed. This study aimed to evaluate the pharmacokinetics of high doses of purified blueberry polyphenols.Methods and results5-month old, ovariectomized Sprague-Dawley rats are acutely dosed with purified blueberry polyphenols (0, 75, 350, and 1000 mg total polyphenols per kg body weight (bw)) and 45 Ca to measure calcium absorption. Blood and urine are collected for 48 h after dosing and phenolic metabolites measured via ultra high-pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The most prominent metabolites are colonically generated cinnamic and hippuric acids. Smaller amounts of other phenolic acids, flavonols, and anthocyanins are also detected. Most metabolites follow a dose-response relationship, though several show saturated absorption. Maximal metabolite concentrations are reached within 12 h for a majority of compounds measured, while some (e.g., hippuric acid) peaked up to 24 h post-dosing. Calcium absorption is significantly increased in the highest dose group (p = 0.03).ConclusionThese results indicate that increased doses of blueberry polyphenols induce changes in intestinal phenolic metabolism and increase calcium absorption.
| S-EPMC9558423 | biostudies-literature
Project description:High dietary intake of calcium has been classified as a probable cause of prostate cancer, although the mechanism underlying the association between dietary calcium and prostate cancer risk is unclear. The vitamin D receptor (VDR) is a key regulator of calcium absorption. In the small intestine, VDR expression is regulated by the CDX-2 transcription factor, which binds a polymorphic site in the VDR gene promoter. We examined VDR Cdx2 genotype and calcium intake, assessed by a food frequency questionnaire, in 533 African-American prostate cancer cases (256 with advanced stage at diagnosis, 277 with localized stage) and 250 African-American controls who participated in the California Collaborative Prostate Cancer Study. We examined the effects of genotype, calcium intake, and diet-gene interactions by conditional logistic regression. Compared with men in the lowest quartile of calcium intake, men in the highest quartile had an approximately twofold increased risk of localized and advanced prostate cancer (odds ratio [OR]?=?2.20, 95% confidence interval [CI]?=?1.40, 3.46), with a significant dose-response. Poor absorbers of calcium (VDR Cdx2 GG genotype) had a significantly lower risk of advanced prostate cancer (OR?=?0.41, 95% CI?=?0.19, 0.90). The gene-calcium interaction was statistically significant (p?=?0.03). Among men with calcium intake below the median (680?mg/day), carriers of the G allele had an approximately 50% decreased risk compared with men with the AA genotype. These findings suggest a link between prostate cancer risk and high intestinal absorption of calcium.
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Project description:Zinc pyrithione (ZnPT) is a coordination complex of zinc and has been used widely as an anti-dandruff agent in shampoos. Many shampoos contain both ZnPT and EDTA, a chelating agent speculated to increase ZnPT absorption, thereby raising concerns about neurotoxicity. Here, we investigated the effect of EDTA on ZnPT absorption by direct comparison of ZnPT and pyrithione (PT) concentrations in shampoo formulations, and by pharmacokinetic analysis of ZnPT, PT, and 2-methanesulfonylpyridine (MSP), the main ZnPT metabolite, in rat plasma or urine following exposure to shampoo containing ZnPT alone or a combination of ZnPT and EDTA. Approximately 17.3% of ZnPT was converted to PT by the addition of EDTA in the shampoo formulation. Plasma ZnPT and PT concentrations were not measured up to 24 hr after treatment with shampoo containing 1% ZnPT or 1% ZnPT + 2% EDTA in all rats. However, PT amount in 24-hr urine sample, MSP concentration in plasma, and MSP amount in 24-hr urine sample were approximately 4-, 2.6-, and 2.7-fold higher, respectively, in the 1% ZnPT + 2% EDTA shampoo group than in the 1% ZnPT shampoo group. As confirmed by the formulation analysis and in vivo pharmacokinetic analysis, the exposure of ZnPT could be increased by the absorption of PT due to partial dissociation of ZnPT into PT.
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Project description:Exposure to chemical and physical factors occur in many occupations. Exposure to ambient pollutants such as noise, heavy metals, drugs enhance free radicals and can cause oxidative stress. The aim of the present project was to investigate noise and lead as two workplace stressors in rats. 20 male rats were assigned into 4 groups randomly. Rats in control group was not exposed to any stressor agent, while the first group was exposed to noise (105 dB, 4 kHz), the second group was exposed to lead acetate (gavage,4 mg/kg), and the last group was exposed to both lead and noise. In order to assess oxidative stress, the serum levels of malondialdehyde (MDA), as a product of lipid peroxidation was measured by thiobarbituric acid and also total antioxidant capacity (TAC) were measured by using ELISA kits. Our research showed significant enhancement in levels of malondialdehyde in exposed groups compare to control group. Also our results showed considerable decrease in levels of TAC in exposed groups compared to control group. Lead and noise exposure for 30 days caused a statistically significant enhancement in MDA level and significant decrease in the serum TAC level. On the other hand, statistically no significant difference was observed between the MDA and TAC levels between exposed groups. Moreover, body weight between exposed groups have decreased compared to control group. The outcomes of this study confirms the effect of noise and lead on lipid peroxidation. However, further studies are needed to clarify the mechanisms of oxidative stress through lead and noise exposure.
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Project description:An isolate of lead-ferritin obtained from soybean seeds sprouted in 25 mM of PbNO3 was introduced into the diet of both iron-deficient and iron non-deficient male rats. After a 21-day administration period, statistical differences in the lead accumulation in the femurs of the rats were noted. Iron-deficient rats accumulated more than four times the amount of lead in their bones than rats without iron-deficiency. No further decrease was observed in haemoglobin concentrations in the groups of animals fed with lead isolates, either iron-deficient or iron non-deficient. Also, no differences in the mean corpuscular haemoglobin (MCH) and mean corpuscular volume (MCV) were observed at the end of the experiment in the group of iron non-deficient rats fed with lead-ferritin isolate compared to the control group of iron non-deficient rats. In the iron-deficient group fed with lead-ferritin isolate, a small increase in haemoglobin concentrations, MCH, MCV and mean corpuscular haemoglobin concentrations (MCHC) was recorded. The results presented in this paper confirm that lead from the tested preparation-lead ferritin isolate-was better absorbed by those rats with induced iron deficiency anaemia. Additionally, we may also suspect based on the obtained results that absorption of ferritin-iron depends on iron status in the body.
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Project description:We investigated the effect of levosimendan on cisplatin (Cis)-induced nephrotoxicity. Rats were divided into four groups (n?=?6). The first and second groups received normal saline (control) and intraperitoneal (i.p.) cisplatin (6?mg/kg) on day 7, respectively. The third and fourth groups received a single intraperitoneal (i.p.) injection of Cis on day 7 and levosimendan (1?mg/kg/day, orally) or vehicle for 10 days, respectively. At day 11, animals were anaesthetized and blood collected and kidneys removed. Another four groups were treated the same as the previous four groups to measure renal blood flow. Cis induced nephrotoxicity as evidenced by biochemical, histopathological and hemodynamic changes. Levosimendan partially reduced Cis-induced increase in plasma urea, creatinine and neutrophil gelatinase-associated lipocalin (NGAL) levels and decrease in creatinine clearance. Levosimendan partially reduced Cis-induced increase in urinary albumin/creatinine ratio, N-Acetyl-?-D-Glucosaminidase (NAG) and kidney Injury Molecule-1 (KIM-1). Levosimendan significantly attenuated the effect of Cis on plasma concentration of plasma tumor necrosis factor-alpha (TNF-?), antioxidant indices [catalase and superoxide dismutase (SOD)] and lipid peroxidation. Cis induced acute tubular necrosis with tubular dilatation, interstitial edema and congestion. Levosimendan attenuated the remarkable renal damage and reduced renal blood flow induced by Cis. In conclusion this study shows that levosimendan has a partial protective effect on Cis-induced nephrotoxicity. The protective effect of levosimendan is shown to be related to its anti-inflammatory, antioxidant and vasodilator effects.
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Project description:Proton pump inhibitors (PPIs) increase osteoporotic fracture risk presumably via hypochlorhydria and consequent reduced fractional calcium absorption (FCA). Existing studies provide conflicting information regarding the direct effects of PPIs on FCA. We evaluated the effect of PPI therapy on FCA. We recruited women at least 5 years past menopause who were not taking acid suppressants. Participants underwent three 24-hour inpatient FCA studies using the dual stable isotope method. Two FCA studies were performed 1 month apart to establish baseline calcium absorption. The third study occurred after taking omeprazole (40?mg/day) for 30 days. Each participant consumed the same foods during all FCA studies; study meals replicated subjects' dietary habits based on 7-day diet diaries. Twenty-one postmenopausal women ages 58?±?7 years (mean?±?SD) completed all study visits. Seventeen women were white, and 2 each were black and Hispanic. FCA (mean?±?SD) was 20%?±?10% at visit 1, 18%?±?10% at visit 2, and 23%?±?10% following 30?±?3 days of daily omeprazole (p?=?.07, ANOVA). Multiple linear regression revealed that age, gastric pH, serum omeprazole levels, adherence to omeprazole, and 25-hydroxyvitamin D levels were unrelated to changes in FCA between study visits 2 and 3. The 1,25-dihydroxyvitamin D(3) level at visit 2 was the only variable (p?=?.049) associated with the change in FCA between visits 2 and 3. PPI-associated hypochlorhydria does not decrease FCA following 30 days of continuous use. Future studies should focus on identifying mechanisms by which PPIs increase the risk of osteoporotic fracture.
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