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3. Investigation of the role of interleukin-6 and hepcidin antimicrobial peptide in the development of anemia with age

Author

McCranor, Bryan J, Langdon, Jacqueline M, Prince, Olivier D, Femnou, Laurette K, Berger, Alan E, Cheadle, Chris, Civin, Curt I, Kim, Airie, Rivera, Seth, Ganz, Tomas, Vaulont, Sophie, Xue, Qian-Li, Walston, Jeremy D, and Roy, Cindy N

Subjects
Hematology, Aging, Anemia, Animals, Female, Hepcidins, Interleukin-6, Mice, Mice, 129 Strain, Mice, Inbred C57BL, Mice, Knockout, Species Specificity, Immunology
Abstract

Anemia is common in older adults and associated with adverse health outcomes in epidemiological studies. A thorough understanding of the complex pathophysiological mechanisms driving anemia in the elderly is lacking; but inflammation, iron restriction, and impaired erythroid maturation are thought to influence the phenotype. We hypothesized that interleukin-6 contributes to this anemia, given its pro-inflammatory activities, its ability to induce hepcidin antimicrobial peptide, and its negative impact on several tissues in older adults. We tested this hypothesis by comparing changes in indices of inflammation, iron metabolism and erythropoiesis in aged C57BL/6 mice to aged mice with targeted deletions of interleukin-6 or hepcidin antimicrobial peptide. Circulating neutrophil and monocyte numbers and inflammatory cytokines increased with age. Decline in hemoglobin concentration and red blood cell number indicated that C57BL/6, interleukin-6 knockout mice, and hepcidin antimicrobial peptide knockout mice all demonstrated impaired erythropoiesis by 24 months. However, the interleukin-6 knock out genotype and the hepcidin antimicrobial peptide knock out genotype resulted in improved erythropoiesis in aged mice. Increased erythropoietic activity in the spleen suggested that the erythroid compartment was stressed in aged C57BL/6 mice compared to aged interleukin-6 knockout mice. Our data suggest C57BL/6 mice are an appropriate mammalian model for the study of anemia with age. Furthermore, although interleukin-6 and hepcidin antimicrobial peptide are not required, they can participate in the development of anemia in aging mice, and could be targeted, pre-clinically, with existing interventions to determine the feasibility of such agents for the treatment of anemia in older adults.

Published
2013

8. Methylene Blue – A Potential Therapeutic Treatment for Sodium Fluoroacetate Poisoning

Author

Pueblo, Erin, primary, Racine, Michelle, additional, Conroy, Matthieu, additional, Khindri, Jai, additional, Jackson, Riley, additional, Tressler, Justin, additional, Jennings, Laura, additional, Sodipo, Oluwaseyi, additional, Thomas, Sarah, additional, Pierce, Samuel, additional, Shaker, David, additional, Tuet, Wing Y., additional, Deley Cox, Vanessa, additional, Wong, Benjamin, additional, and McCranor, Bryan J., additional

Published
2022
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11. Methylene blue and monosodium glutamate improve neurologic signs after fluoroacetate poisoning

Author

DeLey Cox, Vanessa E., primary, Hartog, Matthew A., additional, Pueblo, Erin, additional, Racine, Michelle, additional, Jennings, Laura, additional, Tressler, Justin, additional, Tuet, Wing Y., additional, Stone, Samuel, additional, Pierce, Samuel A., additional, Thompson, Lily, additional, Dukes, Aliyah, additional, Hoard‐Fruchey, Heidi, additional, Wong, Benjamin, additional, and McCranor, Bryan J., additional

Published
2020
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13. Effects of Aerosolized Carfentanil on Cardiac Function in Ferrets

Author

Pueblo, Erin, primary, Tuet, Wing Y., additional, Racine, Michelle, additional, Tressler, Justin, additional, Jennings, Laura, additional, Stone, Samuel, additional, Pierce, Samuel, additional, Dukes, Aliyah, additional, DeLey Cox, Vanessa E., additional, Wong, Benjamin, additional, and McCranor, Bryan J., additional

Published
2020
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17. The cardiopulmonary effects of sodium fluoroacetate (1080) in Sprague-Dawley rats

Author

McCranor, Bryan J., primary, Young, Talearia D., additional, Tressler, Justin, additional, Jennings, Laura, additional, Irwin, James, additional, Alli, Nazira A., additional, Abilez, Marilynda K., additional, Stone, Samuel, additional, Racine, Michelle, additional, Devorak, Jennifer L., additional, Sciuto, Alfred M., additional, and Wong, Benjamin, additional

Published
2019
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25. Lipid-lowering effects of ethyl 2-phenacyl-3-aryl-1H-pyrrole- 4-carboxylates in rodents.

Author

Holub JM, O'Toole-Colin K, Getzel A, Argenti A, Evans MA, Smith DC, Dalglish GA, Rifat S, Wilson DL, Taylor BM, Miott U, Glersaye J, Lam KS, McCranor BJ, Berkowitz JD, Miller RB, Lukens JR, Krumpe K, Gupton JT, and Burnham BS

Subjects
Acetophenones chemistry, Animals, Atorvastatin, Carboxylic Acids chemical synthesis, Cholesterol, HDL blood, Fatty Acids, Monounsaturated chemistry, Fluvastatin, Heptanoic Acids chemistry, Hypolipidemic Agents chemical synthesis, Indoles chemistry, Lipoproteins, LDL blood, Male, Mice, Pyrroles chemical synthesis, Rats, Rats, Sprague-Dawley, Carboxylic Acids chemistry, Carboxylic Acids pharmacology, Hypolipidemic Agents chemistry, Hypolipidemic Agents pharmacology, Pyrroles chemistry, Pyrroles pharmacology
Abstract

A series of substituted 2-phenacyl-3-phenyl-1H-pyrrole-4-carboxylates were prepared from substituted acetophenones in 6 steps. The final condensations between a chloroenal and an aminoketone were carried out under neutral conditions in parallel to yield the series listed below. Selected pyrrole derivatives proved to be potent hypolipidemic agents lowering serum triglyceride concentrations in CF-1 male mice after 14 days of I.P. administration. One agent orally lowered serum cholesterol in Sprague-Dawley male rats at 2mg/kg/day after 14 days. The agents demonstrated a lowering of mouse serum LDL- cholesterol levels and selected compounds showed an elevation of serum HDL-cholesterol levels. The cholesterol concentrations in the liver were raised while the cholesterol and triglyceride contents of the aorta were significantly lowered by the selected trisubstituted pyrrole.

Published
2004
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