scholarly journals Unlike Glycerophosphocholine or Choline Chloride, Dietary Phosphatidylcholine Does Not Increase Plasma Trimethylamine-N-Oxide Levels in Sprague-Dawley Rats

Metabolites ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 64
Author(s):  
Bungo Shirouchi ◽  
Ayano Fukuda ◽  
Taiki Akasaka

Choline, betaine, and L-carnitine are transformed into trimethylamine (TMA) by gut microbiota, absorbed into the liver, and oxidized into trimethylamine-N-oxide (TMAO) by flavin-containing monooxygenases. Elevated TMAO levels may negatively affect human health. As phosphatidylcholine (PC) is the main source of dietary choline, its intake or PC-rich foods may be harmful to human health; however, quantitative comparative information among dietary choline compounds (PC, glycerophosphocholine [GPC], and choline chloride [CC]) regarding in vivo generation of TMAO is lacking. Here, we compared the effects of PC, GPC, and CC on plasma TMAO levels in rats. Furthermore, we investigated their effects on gut microbiota at the genus level. Dietary PC did not affect plasma TMAO levels, whereas dietary GPC and CC significantly increased them. At the genus level, plasma TMAO levels were significantly negatively correlated with relative abundances of Anaerotruncus, Actinomyces, Enterococcus, Dialister, Clostridium XIVa, and Granulicatella; they were significantly positively correlated with that of Coprobacter. Moreover, the relative abundances of Anaerotruncus and Coprobacter were found to predict plasma TMAO levels. Therefore, dietary PC, unlike GPC or CC, does not increase plasma TMAO levels in rats. Furthermore, several gut microbes are associated with changes in plasma TMAO levels in rats fed with choline compounds.

Author(s):  
Shu-Chieh Hu ◽  
Matthew S Bryant ◽  
Estatira Sepehr ◽  
Hyun-Ki Kang ◽  
Raul Trbojevich ◽  
...  

Abstract The tobacco-specific nitrosamine NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone] is found in tobacco products and tobacco smoke. NNK is a potent genotoxin and human lung carcinogen; however, there are limited inhalation data for the toxicokinetics (TK) and genotoxicity of NNK in vivo. In the present study, a single dose of 5x10−5, 5x10−3, 0.1, or 50 mg/kg body weight (BW) of NNK, 75% propylene glycol (vehicle control), or air (sham control) was administered to male Sprague-Dawley (SD) rats (9-10 weeks age) via nose-only inhalation (INH) exposure for 1 hour. For comparison, the same doses of NNK were administered to male SD rats via intraperitoneal (IP) injection and oral gavage (PO). Plasma, urine, and tissue specimens were collected at designated timepoints and analyzed for levels of NNK and its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and tissue levels of DNA adduct O6-methylguanine by LC/MS/MS. TK data analysis was performed using a non-linear regression program. For the genotoxicity subgroup, tissues were collected at 3 hours post-dosing for comet assay analysis. Overall, the TK data indicated that NNK was rapidly absorbed and metabolized extensively to NNAL after NNK administration via the three routes. The IP route had the greatest systemic exposure to NNK. NNK metabolism to NNAL appeared to be more efficient via INH than IP or PO. NNK induced significant increases in DNA damage in multiple tissues via the three routes. The results of this study provide new information and understanding of the toxicokinetics and genotoxicity of NNK.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Himanshu Kushwah ◽  
Nidhi Sandal ◽  
Meenakshi Chauhan ◽  
Gaurav Mittal

Abstract Background Uncontrolled bleeding is one of the primary reasons for preventable death in both civilian trauma and military battle field. This study evaluates in vitro and in vivo hemostatic potential of four biopolymeric natural gums, namely, gum tragacanth, guar gum, xanthan gum, and gum acacia. In vitro evaluation of whole blood clotting time and erythrocyte agglutination assay were carried out. In vitro cytotoxicity studies with respect to each gum were done in human lymphocytes to ascertain percent cell viability. In vivo hemostatic potential of each gum (as sponge dressing and powder form) was evaluated in Sprague Dawley rats using tail bleeding assay and compared with commercially available hemostatic sponge. Other important parameters like (a) time taken for complete hemostasis, (b) amount of blood absorbed, (c) adherence strength of developed hemostatic dressing(s), (d) incidence of re-bleeding, and (e) survival of animals were also studied. Results Of the four test gums studied, xanthan gum (@3mg/ml of blood) and gum tragacanth (@35mg/ml of blood) were able to clot blood in least time (58.75±6.408 s and 59.00±2.082 s, respectively) and exhibited very good hemostatic potential in vitro. Except for xanthan gum, all other test gums did not exhibit any significant cytotoxicity at different time points till 24 h. In rat tail bleeding experiments, gum tragacanth sponge dressing and powder achieved hemostasis in least time (156.2±12.86 s and 76±12.55 s, respectively) and much earlier than commercially available product (333.3±38.84 s; p˂0.01). Conclusion Results indicate potential of gum tragacanth to be developed into a suitable hemostatic product.


1991 ◽  
Vol 7 (3) ◽  
pp. 125-139 ◽  
Author(s):  
David R. Bevan ◽  
David M. Ruggio

To evaluate health risks associated with exposure to particulates in the environment, it is necessary to quantify the bioavailability of carcinogens associated with the particulates. Direct analysis of bioavailability in vivo is most readily accomplished by adsorbing a radiolabeled form of the carcinogen to the particulate. A sam ple of native diesel particulate collected from an Oldsmobile die sel engine that contained 1.03 μ g benzo[ a] pyrene ( BaP)/ g particulate was supplemented with exogenous [ 3 H]- BaP to pro duce a particulate containing 2.62 μ g BaP/g. To insure that elu tion of BaP from native and [3 H] -BaP-supplemented particulate was similar, in vitro analyses were performed. When using phos pholipid vesicles composed of dimyristoylphosphatidylcholine (DMPC), 1.52% of total BaP was eluted from native particulate into the vesicles in 18 hrs; from [ 3 H] -BaP supplemented particu late, 1.68% was eluted. Using toluene as eluent, 2.55% was eluted from native particulate, and 8.25% from supplemented particulate, in 6 hrs. Supplemented particulate was then instilled intratracheally into male Sprague-Dawley rats and distribution of radioactivity was analyzed at selected times over 3 days. About 50% of radioactivity remained in lungs at 3 days following instil lation, with 30% being excreted into feces and the remainder dis tributed throughout the organs of the rats. To estimate the amount of radioactivity that entered feces through swallowing of a portion of the instilled dose, [3 H] -BaP-supplemented particu late was instilled intratracheally into rats that had a cannula sur gically implanted in the bile duct. Rate of elimination of radio activity into bile was monitored; 10.6% of radioactivity was re covered in 6 hr, an amount slightly lower than the 12.8% ex creted in 6 hrs into feces of animals with intact bile ducts. Our studies provide a quantitative description of the distribution of BaP and its metabolites following intratracheal instillation of diesel particulate. Because rates of elution of BaP in vitro are similar for native diesel particulate and particulate with supple mental [ 3H] -BaP, our results provide a reasonable estimate of the bioavailability in vivo of BaP associated with diesel particu late.


2016 ◽  
Vol 3 (4) ◽  
pp. 167-175 ◽  
Author(s):  
Jiang Pu ◽  
Yuanyuan Deng ◽  
Xiaoyan Tan ◽  
Gaofeng Chen ◽  
Cong Zhu ◽  
...  

2012 ◽  
Vol 303 (8) ◽  
pp. R850-R860 ◽  
Author(s):  
Miriam Goebel-Stengel ◽  
Andreas Stengel ◽  
Lixin Wang ◽  
Gordon Ohning ◽  
Yvette Taché ◽  
...  

Various molecular forms of CCK reduce food intake in rats. Although CCK-8 is the most studied form, we reported that CCK-58 is the only detectable endocrine peptide form in rats. We investigated the dark-phase rat chow intake pattern following injection of CCK-8 and CCK-58. Ad libitum-fed male Sprague-Dawley rats were intraperitoneally injected with CCK-8, CCK-58 (0.6, 1.8, and 5.2 nmol/kg), or vehicle. Food intake pattern was assessed during the dark phase using an automated weighing system that allowed continuous undisturbed monitoring of physiological eating behavior. Both CCK-8 and CCK-58 dose dependently reduced 1-h, dark-phase food intake, with an equimolar dose of 1.8 nmol being similarly effective (−49% and −44%). CCK-58 increased the latency to the first meal, whereas CCK-8 did not. The intermeal interval was reduced after CCK-8 (1.8 nmol/kg, −41%) but not after CCK-58. At this dose, CCK-8 increased the satiety ratio by 80% and CCK-58 by 160%, respectively, compared with vehicle. When behavior was assessed manually, CCK-8 reduced locomotor activity (−31%), whereas grooming behavior was increased (+59%). CCK-58 affected neither grooming nor locomotor activity. In conclusion, reduction of food intake by CCK-8 and CCK-58 is achieved by differential modulation of food intake microstructure and behavior. These data highlight the importance of studying the molecular forms of peptides that exist in vivo in tissue and circulation of the animal being studied.


2000 ◽  
Vol 88 (3) ◽  
pp. 1036-1042 ◽  
Author(s):  
Peter A. Farrell ◽  
Jazmir M. Hernandez ◽  
Mark J. Fedele ◽  
Thomas C. Vary ◽  
Scot R. Kimball ◽  
...  

Translational control of protein synthesis depends on numerous eukaryotic initiation factors (eIFs) and we have previously shown ( Am. J. Physiol. Endocrinol. Metab. 276: E721–E727, 1999) that increases in one factor, eIF2B, are associated with increases in rates of protein synthesis after resistance exercise in rats. In the present study we investigated whether the eIF4E family of initiation factors is also involved with an anabolic response to exercise. Male Sprague-Dawley rats either remained sedentary ( n = 6) or performed acute resistance exercise ( n = 6), and rates of protein synthesis were assessed in vivo 16 h after the last session of resistance exercise. eIF4E complexed to eIF4G (eIF4E ⋅ eIF4G), eIF4E binding protein 1 (4E-BP1) complexed to eIF4E, and phosphorylation state of eIF4E and 4E-BP1 (γ-form) were assessed in gastrocnemius. Rates of protein synthesis were higher in exercised rats compared with sedentary rats [205 ± 8 (SE) vs. 164 ± 5.5 nmol phenylalanine incorporated ⋅ g muscle−1 ⋅ h−1, respectively; P < 0.05]. Arterial plasma insulin concentrations were not different between the two groups. A trend ( P = 0.09) for an increase in eIF4E ⋅ eIF4G with exercise was noted; however, no statistically significant differences were observed in any of the components of the eIF4E family in response to resistance exercise. These new data, along with our previous report on eIF2B, suggest that the regulation of peptide chain initiation after exercise is more dependent on eIF2B than on the eIF4E system.


1981 ◽  
Vol 59 (2) ◽  
pp. 75-82 ◽  
Author(s):  
M. Ishaque ◽  
C. Adapoe ◽  
L. Kato

Energy coupling mechanisms of Mycobacterium lepraemurium isolated from Sprague-Dawley rats lepromata were investigated. Cell-free extracts catalyzed phosphorylation coupled to the oxidation of generated NADH, added NADH, and succinate yielding P/O ratios of approximately 0.8, 0.6, and 0.4, respectively. Ascorbate oxidation alone or in the presence of cytochrome c or N,N,N′,N′-tetramethyl-p-phenylenediamine was not coupled to ATP synthesis.The oxidative phosphorylation was completely uncoupled by 2,4-dinitrophenol, 2,6-dibromophenol, pentachlorophenol, m-chlorocarbonylcyanide phenylhydrazone, dicumarol, and gramicidin at concentrations which did not cause any inhibition of oxygen uptake. While the NADH oxidation and associated phosphate esterification was markedly sensitive to rotenone and other flavoprotein inhibitors, these inhibitors had no effect, however, on the phosphorylation coupled to succinate oxidation. The respiratory chain inhibitors such as antimycin A or 2-n-heptyl-4-hydroxyquinoline-N-oxide, and cyanide were the potent inhibitors of the phosphorylation associated with the oxidation of NADH and succinate. The ATP formation coupled to the oxidation of NADH and succinate was also inhibited by oligomycin as well as by the thiol-binding agents, p-hydroxymercuribenzoate and N-ethylmaleimide. The results indicated that NADH and succinate oxidation by in vivo grown M. lepraemurium was mediated by oxidative enzymes involving first and second energy coupling sites.


2009 ◽  
Vol 101 (3) ◽  
pp. 1679-1689 ◽  
Author(s):  
Kip A. Ludwig ◽  
Rachel M. Miriani ◽  
Nicholas B. Langhals ◽  
Michael D. Joseph ◽  
David J. Anderson ◽  
...  

In this study, we propose and evaluate a technique known as common average referencing (CAR) to generate a more ideal reference electrode for microelectrode recordings. CAR is a computationally simple technique, and therefore amenable to both on-chip and real-time applications. CAR is commonly used in EEG, where it is necessary to identify small signal sources in very noisy recordings. To study the efficacy of common average referencing, we compared CAR to both referencing with a stainless steel bone-screw and a single microelectrode site. Data consisted of in vivo chronic recordings in anesthetized Sprague-Dawley rats drawn from prior studies, as well as previously unpublished data. By combining the data from multiple studies, we generated and analyzed one of the more comprehensive chronic neural recording datasets to date. Reference types were compared in terms of noise level, signal-to-noise ratio, and number of neurons recorded across days. Common average referencing was found to drastically outperform standard types of electrical referencing, reducing noise by >30%. As a result of the reduced noise floor, arrays referenced to a CAR yielded almost 60% more discernible neural units than traditional methods of electrical referencing. CAR should impart similar benefits to other microelectrode recording technologies—for example, chemical sensing—where similar differential recording concepts apply. In addition, we provide a mathematical justification for CAR using Gauss-Markov theorem and therefore help place the application of CAR into a theoretical context.


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