HEPATOLOGY, Vol. 61, No. 5, 2015
between sarcopenia and nonalcoholic fatty liver disease in future longitudinal studies. HO CHEOL HONG, M.D. KYUNG MOOK CHOI, M.D., PH.D. Korea University Guro Hospital Seoul, Korea
References 1. Baumgartner RN, Koehler KM, Gallagher D, Romero L, Heymsfield SB, Ross RR, et al. Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol 1998;147:755-763. 2. Newman AB, Kupelian V, Visser M, Simonsick E, Goodpaster B, Nevitt M, et al. Sarcopenia: alternative definitions and associations with lower extremity function. J Am Geriatr Soc 2003;51:1602-1609.
CORRESPONDENCE
1765
3. Janssen I, Heymsfield SB, Ross R. Low relative skeletal muscle mass (sarcopenia) in older persons is associated with functional impairment and physical disability. J Am Geriatr Soc 2002;50:889-896. 4. Lim S, Kim JH, Yoon JW, Kang SM, Choi SH, Park YJ, et al. Sarcopenic obesity: prevalence and association with metabolic syndrome in the Korean Longitudinal Study on Health and Aging (KLoSHA). Diabetes Care 2010;33:1652-1654. 5. Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, et al. Sarcopenia: European consensus on definition and diagnosis: report of the European Working Group on Sarcopenia in Older People. Age Ageing 2010;39:412-423.
Author names in bold designate shared co-first authorship. C 2015 by the American Association for the Study of Liver Diseases. Copyright V View this article online at wileyonlinelibrary.com. DOI 10.1002/hep.27751 Potential conflict of interest: Nothing to report.
The b-Adrenoceptor Agonist Isoproterenol Rescues Acetaminophen-Injured Livers: Is It Really Safe? 2
Department of Orthopedic Surgery The Second Affiliated Hospital of Wenzhou Medical University Wenzhou, China
To the Editor: We read with great interest the article by Soeda et al.,1 who reported that the sympathetic nervous system (SNS) agonist, isoproterenol, can result in expansion of the hepatic progenitor cell (HPC) population and can ameliorate acetaminophen (APAP)induced acute liver injury through the Wnt pathway, thus implicating isoproterenol as a putative novel therapeutic approach for APAP-induced hepatotoxicity. However, there are alternative explanations based on published findings. First, in dopamine b-hydroxylase-deficient (Dbh2/2) mice, there were more ß-adrenergic receptors in the state of high affinity than in the wild-type mice.2 After treatment with isoproterenol, the SNS could exert greater effects that could lead to myocardial injury3 and hyperglycemia.4 Evidence indicates that myocardial injury could also result in liver injury,5 and hepatic oxidative stress induced by acute hyperglycemia could aggravate liver damage to some extent.6 These could be factors in an increase in HPC numbers. Hence, the expansion of HPCs in Dbh2/2 mice in this experiment may be a result of the indirect effects of isoproterenol-induced liver injury. Do the researchers have any data concerning the isoproterenol-induced liver injury in Dbh2/2 mice? Second, isoproterenol could lead to cardiotoxicity, dyslipidemia,7 and vascular oxidative stress and endothelial dysfunction,8 which could be a second mechanism by which the liver is damaged. Is it really safe to consider administration of isoproterenol? Do the researchers have any data about the long-term consequences of isoproterenol therapy?
ZHUOLIN ZOU, M.D.1 ZHONGHAI SHEN, M.D.2 YIJING CAI, M.D.1 YI CHEN, M.D.1 SI CHEN, M.D.1 YONGPING CHEN, M.D.1 1 Department of Infectious Disease The First Affiliated Hospital of Wenzhou Medical University Wenzhou, China
References 1. Soeda J, Mouralidarane A, Ray S, Novelli M, Thomas S, Roskams T, et al. The beta-adrenoceptor agonist Isoproterenol rescues acetaminopheninjured livers through increasing progenitor numbers via Wnt. HEPATOLOGY 2014 June 13. doi: 10.1002/hep.27266. [Epub ahead of print] 2. Carson RP, Robertson D. Genetic manipulation of noradrenergic neurons. J Pharmacol Exp Ther 2002;301:410-417. 3. Sahu BD, Anubolu H, Koneru M, Kumar JM, Kuncha M, Rachamalla SS, Sistla R. Cardioprotective effect of embelin on isoproterenol-induced myocardial injury in rats: possible involvement of mitochondrial dysfunction and apoptosis. Life Sci 2014;107:59-67. 4. Thackeray JT, Radziuk J, Harper ME, Suuronen EJ, Ascah KJ, Beanlands RS, Dasilva JN. Sympathetic nervous dysregulation in the absence of systolic left ventricular dysfunction in a rat model of insulin resistance with hyperglycemia. Cardiovasc Diabetol 2011;10:75. 5. von Kanel R, Abbas CC, Begre S, Gander ML, Saner H, Schmid JP. Association between posttraumatic stress disorder following myocardial infarction and liver enzyme levels: a prospective study. Dig Dis Sci 2010;55:2614-2623. 6. Ling PR, Mueller C, Smith RJ, Bistrian BR. Hyperglycemia induced by glucose infusion causes hepatic oxidative stress and systemic inflammation, but not STAT3 or MAP kinase activation in liver in rats. Metabolism 2003;52:868-874. 7. Selvaraj P, Pugalendi KV. Efficacy of hesperidin on plasma, heart and liver tissue lipids in rats subjected to isoproterenol-induced cardiotoxicity. Exp Toxicol Pathol 2012;64:449-452. 8. Davel AP, Brum PC, Rossoni LV. Isoproterenol induces vascular oxidative stress and endothelial dysfunction via a Gia-coupled beta2-adrenoceptor signaling pathway. PLoS One 2014;9:e91877. C 2015 by the American Association for the Study of Liver Diseases. Copyright V View this article online at wileyonlinelibrary.com. DOI 10.1002/hep.27374 Potential conflict of interest: Nothing to report.
between sarcopenia and nonalcoholic fatty liver disease in future longitudinal studies. HO CHEOL HONG, M.D. KYUNG MOOK CHOI, M.D., PH.D. Korea University Guro Hospital Seoul, Korea
References 1. Baumgartner RN, Koehler KM, Gallagher D, Romero L, Heymsfield SB, Ross RR, et al. Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol 1998;147:755-763. 2. Newman AB, Kupelian V, Visser M, Simonsick E, Goodpaster B, Nevitt M, et al. Sarcopenia: alternative definitions and associations with lower extremity function. J Am Geriatr Soc 2003;51:1602-1609.
CORRESPONDENCE
1765
3. Janssen I, Heymsfield SB, Ross R. Low relative skeletal muscle mass (sarcopenia) in older persons is associated with functional impairment and physical disability. J Am Geriatr Soc 2002;50:889-896. 4. Lim S, Kim JH, Yoon JW, Kang SM, Choi SH, Park YJ, et al. Sarcopenic obesity: prevalence and association with metabolic syndrome in the Korean Longitudinal Study on Health and Aging (KLoSHA). Diabetes Care 2010;33:1652-1654. 5. Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, et al. Sarcopenia: European consensus on definition and diagnosis: report of the European Working Group on Sarcopenia in Older People. Age Ageing 2010;39:412-423.
Author names in bold designate shared co-first authorship. C 2015 by the American Association for the Study of Liver Diseases. Copyright V View this article online at wileyonlinelibrary.com. DOI 10.1002/hep.27751 Potential conflict of interest: Nothing to report.
The b-Adrenoceptor Agonist Isoproterenol Rescues Acetaminophen-Injured Livers: Is It Really Safe? 2
Department of Orthopedic Surgery The Second Affiliated Hospital of Wenzhou Medical University Wenzhou, China
To the Editor: We read with great interest the article by Soeda et al.,1 who reported that the sympathetic nervous system (SNS) agonist, isoproterenol, can result in expansion of the hepatic progenitor cell (HPC) population and can ameliorate acetaminophen (APAP)induced acute liver injury through the Wnt pathway, thus implicating isoproterenol as a putative novel therapeutic approach for APAP-induced hepatotoxicity. However, there are alternative explanations based on published findings. First, in dopamine b-hydroxylase-deficient (Dbh2/2) mice, there were more ß-adrenergic receptors in the state of high affinity than in the wild-type mice.2 After treatment with isoproterenol, the SNS could exert greater effects that could lead to myocardial injury3 and hyperglycemia.4 Evidence indicates that myocardial injury could also result in liver injury,5 and hepatic oxidative stress induced by acute hyperglycemia could aggravate liver damage to some extent.6 These could be factors in an increase in HPC numbers. Hence, the expansion of HPCs in Dbh2/2 mice in this experiment may be a result of the indirect effects of isoproterenol-induced liver injury. Do the researchers have any data concerning the isoproterenol-induced liver injury in Dbh2/2 mice? Second, isoproterenol could lead to cardiotoxicity, dyslipidemia,7 and vascular oxidative stress and endothelial dysfunction,8 which could be a second mechanism by which the liver is damaged. Is it really safe to consider administration of isoproterenol? Do the researchers have any data about the long-term consequences of isoproterenol therapy?
ZHUOLIN ZOU, M.D.1 ZHONGHAI SHEN, M.D.2 YIJING CAI, M.D.1 YI CHEN, M.D.1 SI CHEN, M.D.1 YONGPING CHEN, M.D.1 1 Department of Infectious Disease The First Affiliated Hospital of Wenzhou Medical University Wenzhou, China
References 1. Soeda J, Mouralidarane A, Ray S, Novelli M, Thomas S, Roskams T, et al. The beta-adrenoceptor agonist Isoproterenol rescues acetaminopheninjured livers through increasing progenitor numbers via Wnt. HEPATOLOGY 2014 June 13. doi: 10.1002/hep.27266. [Epub ahead of print] 2. Carson RP, Robertson D. Genetic manipulation of noradrenergic neurons. J Pharmacol Exp Ther 2002;301:410-417. 3. Sahu BD, Anubolu H, Koneru M, Kumar JM, Kuncha M, Rachamalla SS, Sistla R. Cardioprotective effect of embelin on isoproterenol-induced myocardial injury in rats: possible involvement of mitochondrial dysfunction and apoptosis. Life Sci 2014;107:59-67. 4. Thackeray JT, Radziuk J, Harper ME, Suuronen EJ, Ascah KJ, Beanlands RS, Dasilva JN. Sympathetic nervous dysregulation in the absence of systolic left ventricular dysfunction in a rat model of insulin resistance with hyperglycemia. Cardiovasc Diabetol 2011;10:75. 5. von Kanel R, Abbas CC, Begre S, Gander ML, Saner H, Schmid JP. Association between posttraumatic stress disorder following myocardial infarction and liver enzyme levels: a prospective study. Dig Dis Sci 2010;55:2614-2623. 6. Ling PR, Mueller C, Smith RJ, Bistrian BR. Hyperglycemia induced by glucose infusion causes hepatic oxidative stress and systemic inflammation, but not STAT3 or MAP kinase activation in liver in rats. Metabolism 2003;52:868-874. 7. Selvaraj P, Pugalendi KV. Efficacy of hesperidin on plasma, heart and liver tissue lipids in rats subjected to isoproterenol-induced cardiotoxicity. Exp Toxicol Pathol 2012;64:449-452. 8. Davel AP, Brum PC, Rossoni LV. Isoproterenol induces vascular oxidative stress and endothelial dysfunction via a Gia-coupled beta2-adrenoceptor signaling pathway. PLoS One 2014;9:e91877. C 2015 by the American Association for the Study of Liver Diseases. Copyright V View this article online at wileyonlinelibrary.com. DOI 10.1002/hep.27374 Potential conflict of interest: Nothing to report.
