scholarly journals Zinc overload in weaned pigs: tissue accumulation, pathology, and growth impacts

2019 ◽  
Vol 31 (4) ◽  
pp. 537-545 ◽  
Author(s):  
Eric R. Burrough ◽  
Carson De Mille ◽  
Nicholas K. Gabler
Keyword(s):  
Zinc Oxide ◽  
Pancreatic Acinar Cell ◽  
High Dose ◽  
Bacterial Disease ◽  
Limited Data ◽  
Mineral Analysis ◽  
Tissue Concentrations ◽  
Specific Serum ◽  
High Dose Treatment ◽  
Serum Zn

Zinc oxide (ZnO) is commonly fed to pigs at pharmacologic concentrations (2,000–3,000 ppm) for the first 3 wk post-weaning to increase growth and reduce enteric bacterial disease. The safety of this high-dose treatment is assumed based upon lower bioavailability of ZnO compared to other common forms of Zn in feed; however, limited data are available regarding the specific serum and tissue concentrations of Zn expected in animals experiencing overload following feeding of excessive ZnO. Fifty-five 3-wk-old pigs were divided into 5 groups receiving various concentrations of ZnO (0–6,000 ppm) for 3 wk. Pigs receiving 6,000 ppm ZnO had higher mean pancreatic Zn concentrations ( p < 0.001) compared to other treatments, and higher pancreatic Zn concentrations were associated with pancreatic acinar cell apoptosis ( p < 0.0001). Hepatic Zn concentrations were highest for pigs receiving 6,000 ppm ZnO (mean ± SEM; 729 ± 264 ppm) and significantly higher than all other groups ( p < 0.0001), with controls having concentrations <60 ppm. Similarly, serum Zn was highest in pigs receiving 6,000 ppm ZnO (4.81 ± 2.31 ppm) and significantly higher than all groups (controls, <1 ppm). Additionally, as pigs became overloaded with Zn, there were significant reductions in serum Cu and both serum and hepatic Se. Hepatic and serum Zn concentrations >500 ppm and >2 ppm, respectively, are indicative of Zn overload, and dietary trace mineral analysis is warranted if expected inclusion rates are ≤3,000 ppm ZnO.

Evaluation of the Effect of Nanoparticles Zinc Oxide/Camellia sinensis Complex on the Kidney of Rats Treated with Monosodium Glutamate: Antioxidant and Histological Approaches

2019 ◽  
Vol 20 (7) ◽  
pp. 542-550 ◽  
Author(s):  
Nahla S. El-Shenawy ◽  
Reham Z. Hamza ◽  
Fawziah A. Al-Salmi ◽  
Rasha A. Al-Eisa
Keyword(s):  
Zinc Oxide ◽  
Camellia Sinensis ◽  
Zinc Oxide Nanoparticles ◽  
Morphological Changes ◽  
Monosodium Glutamate ◽  
Oxide Nanoparticles ◽  
High Dose ◽  
Enzymatic Antioxidants ◽  
Zno Nps ◽  
Tea Extract

Background: Zinc oxide nanoparticles (ZnO NPs) are robustly used biomedicine. Moreover, no study has been conducted to explore the consequence of green synthesis of ZnO NPs with Camellia sinensis (green tea extract, GTE) on kidneys of rats treated with monosodium glutamate (MSG). Methods: Therefore, the objective of the research was designed to explore the possible defensive effect of GTE/ZnO NPs against MSG-induced renal stress investigated at redox and histopathological points. Results: The levels of urea and creatinine increased as the effect of a high dose of MSG, in addition, the myeloperoxidase and xanthine oxidase activates were elevated significantly with the high dose of MSG. The levels of non-enzymatic antioxidants (uric acid, glutathione, and thiol) were decreased sharply in MSG-treated rats as compared to the normal group. Conclusion: The data displayed that GTE/ZnO NPs reduced the effects of MSG significantly by reduction of the level peroxidation and enhancement intracellular antioxidant. These biochemical findings were supported by histopathology evaluation, which showed minor morphological changes in the kidneys of rats.

P162 clinical pharmacokinetics of etoposide during high-dose treatment in relation to toxicity

1994 ◽  
Vol 2 (1-2) ◽  
pp. 159
Author(s):  
S. Stremetzne ◽  
U. Jaehde ◽  
J. Beyer ◽  
J. Steuer ◽  
W. Siegert ◽  
...  
Keyword(s):  
High Dose ◽  
Clinical Pharmacokinetics ◽  
Dose Treatment ◽  
High Dose Treatment

Ferulic Acid Dose Effect on Pharmacokinetics of Glimepiride and its Metabolite Hydroxy Glimepiride in Rats

2021 ◽  
Vol 17 ◽  
Author(s):  
Yuxian Lin ◽  
Faxin Sun ◽  
Jinlai Liu ◽  
Qinghua Weng ◽  
Lijun Jin ◽  
...  
Keyword(s):  
Ferulic Acid ◽  
Low Dose ◽  
Dose Effect ◽  
High Dose ◽  
Intragastric Administration ◽  
Healthy Male ◽  
Sprague Dawley ◽  
Sd Rats ◽  
High Dose Treatment ◽  
Significant Difference

Background: To mitigate diabetes and its complications in cardiovascular diseases, the antidiabetic agent glimepiride is usually administered with ferulic acid concomitantly in clinics. However, both drugs are prone to be metabolized partly by CYP2C9, thus they have the potential drug-drug interaction affecting the safety and efficacy. Objective: This project aimed to evaluate the pharmacokinetic (PK) effects of ferulic acid (FA) on glimepiride (GLM) and its metabolite hydroxy glimepiride (OH-GLM) in plasma by using the HPLC-MS/MS method. Methods: Healthy male Sprague Dawley (SD) rats were randomly divided into three groups. They received intragastric administration of 0.5% sodium carboxymethyl cellulose (CMC), low-dose FA (20 mg•kg-1), and high-dose FA (40 mg•kg-1) for 8 days, respectively. Rats were given 0.5% sodium CMC or FA on the last day and then uniformly given 1.0 mg•kg-1 glimepiride by gavage. Blood samples were obtained from retro-orbital plexus at the time points of 0.167, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h after administration. Plasma samples were analyzed for GLM and its metabolite OH-GLM on an HPLC-MS/MS system. Results: No statistically significant difference was found in the effect of low-dose FA on the pharmacokinetics of GLM. High-dose FA significantly decreased Cmax of GLM by 30.05% and CLz/F of OH-GLM by 47.45%. It also increased Tmax and t1/2z of GLM by 95.87% and 140.00%. Conclusion: Low-dose FA did not alter GLM metabolism, while high-dose treatment of FA caused pharmacokinetics interaction with GLM in rats.

ITI Treatment is not First-Choice Treatment in Children with Hemophilia A and Low-Responding Inhibitors: Evidence from a PedNet Study

2020 ◽  
Vol 120 (08) ◽  
pp. 1166-1172
Author(s):  
H. Marijke van den Berg ◽  
Maria Elisa Mancuso ◽  
Christoph Königs ◽  
Roseline D'Oiron ◽  
Helen Platokouki ◽  
...  
Keyword(s):  
Hemophilia A ◽  
Real Life ◽  
Tolerance Induction ◽  
High Dose ◽  
Severe Hemophilia ◽  
Limited Data ◽  
Treatment Regimens ◽  
First Choice ◽  
Lost To Follow Up

Abstract Background Limited data exist on the clinical impact of low-responding inhibitors and the requirement for immune tolerance induction (ITI) treatment to establish tolerance, reduce bleeding, and improve outcome. The aim of this article is to describe the therapeutic management of children with severe hemophilia A and low-responding inhibitors and its effect on bleeding phenotype. Methods The REMAIN (Real-life Management of Inhibitors) study is a satellite study of the PedNet registry. It included unselected children with severe hemophilia A (factor VIII [FVIII] < 0.01 IU/mL) born between January 1, 1990 and December 31, 2009 who developed clinically relevant inhibitors and were followed-up for at least 3 years after the first positive inhibitor test. Results A total of 260 patients with inhibitors were identified and 68 of them (26%) had low-responding inhibitors (peak < 5 BU/mL). Five patients were lost to follow-up and 63 were included in this study. The median follow-up was 3.7 years (interquartile range: 3.0–7.5). ITI was started in 51/63 (81%) patients. The median time from ITI start to first negative inhibitor titer was similar with low-dose and high-dose ITI regimens (2.5 and 3.1 months, respectively). Ten of the 12 patients who did not receive ITI were treated with regular prophylaxis and reached a negative titer after a median of 6.5 months. Bleeding rate was low in all patients with no difference between treatment regimens. Conclusion In children with low-responding inhibitors negative titers were reached with regular FVIII treatment irrespective of the regimen (i.e., prophylaxis or ITI).

scholarly journals Effects of Dietary Supplementation of Humic Acid Sodium and Zinc Oxide on Growth Performance, Immune Status and Antioxidant Capacity of Weaned Piglets

Animals ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 2104
Author(s):  
Qi Wang ◽  
Jiafu Ying ◽  
Peng Zou ◽  
Yuanhao Zhou ◽  
Baikui Wang ◽  
...  
Keyword(s):  
Zinc Oxide ◽  
Body Weight ◽  
Antioxidant Capacity ◽  
Growth Performance ◽  
Immune Status ◽  
Immunoglobulin M ◽  
Control Group ◽  
High Dose ◽  
Weaned Piglets ◽  
Basic Diet

At present, the widespread use of high-dose zinc oxide and antibiotics to prevent post-weaning diarrhea (PWD) in piglets has caused serious environmental problems. To solve this problem, we studied the effect of HNa as a substitute for zinc oxide (ZnO) and antibiotics on the growth performance, immune status, and antioxidant capacity of piglets. Seventy-two weaned piglets (body weight = 7.42 ± 0.85 kg, 26-d-old) were distributed in a randomized 2 × 3 factorial design (two sexes and three treatments) with six replicates of four piglets each. The three treatments were the control diet (basic diet), HNa diet (basic diet + 2000 mg/kg sodium humate), and ZoA group (basic diet + 1600 mg/kg zinc oxide + 1000 mg/kg oxytetracycline calcium). ANOVA and Chi-square tests were applied to compare the means (p < 0.05) between treatments. The results showed that body weight at 16 and 30 d and the average daily gain of piglets fed with HNa or ZoA were significantly higher (p < 0.05) than the control group. Supplementing HNa or ZoA significantly increased (p < 0.05) the level of immunoglobulin M and G, and reduced (p < 0.05) the concentration of inflammatory factors such as tumor necrosis factor-alpha (TNF-α), interleukins IL-6 and IL-1β, myeloperoxidase (MPO), and diamine oxidase (DAO). Furthermore, dietary HNa or ZnO significantly reduced (p < 0.05) the level of total antioxidant capacity (T-AOC) and malondialdehyde (MDA) compared with the control group. ZoA treatment showed an upward trend of IgA level and a downward trend of the concentration of lipopolysaccharide (LPS) and catalase (CAT). Overall, the study demonstrated that the addition of HNa in the diet partially replaced antibiotics and ZnO to improve the growth performance, immune function, and antioxidant capacity of weaned piglets, and maintained a good preventive effect on piglet diarrhea.

Genotoxicity evaluation of zinc oxide nanoparticles in Swiss mice after oral administration using chromosomal aberration, micronuclei, semen analysis, and RAPD profile

2017 ◽  
Vol 33 (11) ◽  
pp. 821-834 ◽  
Author(s):  
Anurag Kumar Srivastav ◽  
Akhilesh Kumar ◽  
Jyoti Prakash ◽  
Dhirendra Singh ◽  
Pankaj Jagdale ◽  
...  
Keyword(s):  
Zinc Oxide ◽  
Oral Administration ◽  
Chromosomal Aberration ◽  
Zinc Oxide Nanoparticles ◽  
Dose Group ◽  
High Dose Group ◽  
Oxide Nanoparticles ◽  
High Dose ◽  
Zno Nps ◽  
Swiss Mice

The expanded uses of zinc oxide nanoparticles (ZnO NPs) have grown rapidly in the field of nanotechnology. Thus, rising production of nanoparticles (NPs) increases the possible risks to the environment and occupationally exposed humans. Hence, it is indispensable to appraise the safety toxicity including genotoxicity for these NPs. In the present study, we have evaluated the genotoxic effect of ZnO NPs after oral administration to Swiss mice at dose levels of 300 and 2000 mg/kg body weight. These doses were administered for 2 days at 24 h apart. Chromosomal aberration (CA) and micronucleus tests were conducted following Organization for Economic Co-operation and Development guidelines. DNA damage was evaluated at 0, 24, 48, and 72 h posttreatment using a randomly amplified polymorphic DNA (RAPD) assay; additionally, semen analyses were also performed at 34.5 days post oral exposure. The reactive oxygen species (ROS), 8-oxo-2′-deoxyguanosine and CAs were increased ( p < 0.05) at the highest dosage (2000 mg/kg) of ZnO NPs compared to controls. Aberrant sperm morphology with reduced sperm count and motility were also present ( p < 0.05) in the high-dose group. Based on the RAPD assay, the genomic template stability within the high-dose group (<90%) was less than the controls (100%). The results suggested that ZnO NPs are mildly genotoxic in a dose-related manner and this toxicity were induced by generation of ROS.

Clinical use of High-Dose Neuroleptics

1994 ◽  
Vol 164 (1) ◽  
pp. 94-96 ◽  
Author(s):  
Steven R. Hirsch ◽  
Thomas R. E. Barnes
Keyword(s):  
British National Formulary ◽  
High Dose ◽  
Clinical Use ◽  
National Formulary ◽  
Public Concern ◽  
Neuroleptic Treatment ◽  
Clinical Issues ◽  
Small Minority ◽  
Dose Treatment ◽  
High Dose Treatment

There has been increasing public concern about the risks of high-dose antipsychotic (neuroleptic) treatment, arising in part from an, as yet unproven, association between high-dose treatment and death in a small minority of patients. The clinical issues related to the use of neuroleptics in doses exceeding the maximum recommended in theBritish National Formulary(BNF) were discussed at the Psychopharmacology Subcommittee. When, if ever, should the recommended doses be exceeded?

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