Mechanism of Pharmacological or Toxicity Effect of Ribavirin on Kidney-Yang Deficiency Syndrome Mice Model Infected with Influenza Virus A Based on Serum Metabolomics
SUN Qi-hui, LI Can, FU Ye-pei, YANG Yong, JIANG Hai-qiang, GONG Li-li, RONG Rong*
Shandong University of Traditional Chinese Medicine, Jinan 250355, China
Abstract��OBJECTIVE To analyze the endogenous metabolite changes in the sera of kidney-yang deficiency syndrome mice infected with influenza virus A after intervention by ribavirin. And to explore the mechanism of pharmacological or toxicity effect of ribavirin. METHODS KM mice were randomly divided into three groups as normal group, model group and ribavirin group. Mice were infected with virus A after fifteen days Kidney-Yang deficiency syndrome was established. Ribavirin group were orally administrated with ribavirin for 6 consecutive days after inoculation, and the other two groups were given with equal volume of saline solution in the same way. Body weight, rectal temperature were recorded daily. Serum samples were collected from mouse 24 h after the last administration for HPLC-TOF/MS analysis. RESULTS The results show that ribavirin has good therapeutic effects on the lung index and high mortality rate of mice model. Compared with normal and model groups, the body weight and rectal temperature of them performed falling continuously. The LC-MS data were analyzed with multivariate statistical analysis and 14 potential metabolic markers were obtained which contained D-glucose, sphinganine, linoleic acid and so on. In ribavirin group, metabolism of linoleic acid, arachidonic acid and sphinganine appeared the trend of normal. And sugar and glycerophospholipid became disorders. CONCLUSION The metabolomics study and pharmacological experiment show that ribavirin might play a role of efficacy in a way that has close correlation with the linoleic acid, arachidonic acid and sphingolipid metabolic pathways. And the toxicity effect may be related to sugar and glycerophospholipid metabolic pathways.
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SUN Qi-hui, LI Can, FU Ye-pei, YANG Yong, JIANG Hai-qiang, GONG Li-li, RONG Rong. Mechanism of Pharmacological or Toxicity Effect of Ribavirin on Kidney-Yang Deficiency Syndrome Mice Model Infected with Influenza Virus A Based on Serum Metabolomics. Chinese Pharmaceutical Journal, 2017, 52(16): 1409-1414.
PENG B M, WANG Q Y, XU X Y. Adverse reaction analysis of Ribavirin Injection [J]. Chin J Clin Rat Drug Use (�ٴ�������ҩ), 2010, 3(15): 103-104.
[2]
WU H, WU T, JU S Y, et al. Analysis of the safety and benefit-risk of ribavirin [J]. Chin J Epidemiol (���в�ѧ��־), 2006, 15(4): 210-213.
[3]
BAO H R. Analysis of acute renal damage induced by Ribavirin Injection [J]. Her Med (ҽҩ����), 2008, 27(8): 1007.
[4]
LINDON J C, HOLMES E, NICHOLSON J K. Metabonomics techniques and applications to pharmaceutical research and development [J]. Pharmacol Res, 2006, 23(6): 1075-1088.
[5]
JIA L Q, ZHEN B X, XU Y, et al. Study on serum metabolite profiling in Pi-deficiency rats based on LC-MS technique[J]. Chin J Integr Tradit West Med (�й�����ҽ�����־) , 2016, 36(3): 359-365.
[6]
LU G Y, SU J, CHEN S H, et al. Effects of herbs of same nature and flavor but different meridian tropism on estradiol-induced Kidney-Yang deficiency in mice [J]. J Tradit Chin Med (��ҩ��), 2011,34(10):70-74.
[7]
YAN B, YANG L P, HUANG J, et al. Effects of pulse therapy with glucocorticoids on metabolism in patients with systemic lupus erythematosus [J]. Chin Pharm J (�й�ҩѧ��־), 2016, 51(8): 1429-1435.
[8]
HU C, TANG X L, LI J, et al. The metabonimics study on mices plasma interveted by the water extract of Scurfpea fruit based on the technology of HPLC-QTOF/MS [J]. Pharmacol Clin Chin Mater Clin Med (��ҩҩ�����ٴ�), 2016, 32(1): 22-25.
[9]
HOFINANOVA J, CIGANEK M, SLAVIK J, et al. Lipid alterations in human colon epithelial cells induced to differentiation and/or apoptosis by butyrate and polyunsaturated fatty acids [J]. J Nutr Biochem, 2012, 23 (6): 539-548.
[10]
ZENG P Y, ZHANG Y, RUI W, et al. The analysis of UPLC-Q-TOF/MS in plasma phospholipids in type 2 diabetic rats [J]. Acta Pharm Sin (ҩѧѧ��), 2015,50(7): 882-886.
[11]
LU D Q, CHENG S L, CHENG J. The metabolism and physiological function of eicosapentaenoic acid and docosahexaenoic acid [J]. J Jiangsu Univ (���մ�ѧѧ��), 1998, 19(3): 29-36.
[12]
SASSA T, SUTO S, OKAYASU Y, et al. A shift in sphingolipid composition from C24 to C16 increases susceptibility to apoptosis in HeLa cells [J]. Biochim Biophys Acta, 2012, 1821(7): 1031-1037.
[13]
SUN J L, LIN H Z, GOU P. Research progress of sphingolipid metabolism and related diseases [J]. Biotechnology (���＼��), 2011, 21(5): 93-97.
[14]
WHEELOCK C E, GOSS V M, BALGOMA D, et al. Application of omics technologies to biomarker discovery in inflammatory lung diseases[J]. Eur Respir J, 2013, 42(3): 802-825.
[15]
SUN Q H, ZHANG J, LI Z Z, et al. Action mechanism of Mahuang Xixin Fuzi decoction for mice with influenza based on metabolomics information [J]. China J Chin Mater Med (�й���ҩ��־), 2017, 42(4): 763-771.
2017, Vol. 52 
