• 中国精品科技期刊
  • 中国高校百佳科技期刊
  • 中国中文核心期刊
  • 中国科学引文数据库核心期刊
Advanced Search
CHENG Liyuan, LIU Wei, GUO Xiaoyan, GE Xiaoai, WANG Dingding, WANG Tao. Effects and mechanism of zidovudine on glucolipid metabolic balance in mice[J]. Journal of China Pharmaceutical University, 2022, 53(3): 340-347. DOI: 10.11665/j.issn.1000-5048.20220312
Citation: CHENG Liyuan, LIU Wei, GUO Xiaoyan, GE Xiaoai, WANG Dingding, WANG Tao. Effects and mechanism of zidovudine on glucolipid metabolic balance in mice[J]. Journal of China Pharmaceutical University, 2022, 53(3): 340-347. DOI: 10.11665/j.issn.1000-5048.20220312
shu

Effects and mechanism of zidovudine on glucolipid metabolic balance in mice

  • 1.

    New Drug Screening Center, Institute of Pharmaceutical Sciences, China Pharmaceutical University, Nanjing 210009

  • 2.

    Nanjing Prevention and Treatment Center for Occupational Diseases, Nanjing 210042, China

Funds: This study was supported by Qinghai Provincial High-end and Innovative 1000 Talents Plan
More Information
  • Received Date: February 14, 2022
  • Revised Date: April 10, 2022
    Graphical Abstract
    • Abstract
  • To study the effects of nucleoside antiviral drug zidovudine (AZT) on the flexibility of global metabolism and liver glucolipid metabolic balance in mice, male ICR mice were given zidovudine intragastric administration for 12 weeks, and their water and food intake was recorded daily.Serum glucose (GLU) and triglyceride (TG) levels and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected after 12 weeks of administration.Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed.HE staining was used to observe the pathological changes of liver.The gene levels of glucose transporter (Glut2), carnitine palmitate transferase (Cpt1α), medium chain acyl-coa dehydrogenase (Mcad), phosphoenolpyruvate carboxykinase (Pepck) and glucose-6-phosphatase (G6pase) were detected by RT-PCR.Western blot was used to detect the protein levels of insulin signaling Akt, P-Akt, Glut2, Mcad and Cpt1α in liver.The results showed that zidovudine significantly decreased lipid metabolism, impaired glucose tolerance, increased liver cell volume, significantly increased liver triglyceride (TG) and non-esterified fatty acid (NEFA) content, increased Glut2 gene expression, down-regulated fatty acid oxidative metabolism genes Cpt1α, Mcad and gluconeogenesis related genes after fasting, and down-regulated protein expression of Cpt1α.The results suggest that zidovudine can induce the disorder of glucose and lipid metabolism after fasting in a dose-dependent manner.
    • FullText(HTML)
    • References (23)
  • [1]
    . Lancet，2019，394：S8.
    [2]
    AIDS and Hepatitis C Professional Group，Society of Infectious Diseases，Chinese Medical Association. Chinese guidelines for diagnosis and treatment of HIV/AIDS （2021 edition）［J］. Chin J Intern Med（中华内科杂志），2021，60（12）：1106-1128.
    [3]
    Sapu?a M，Suchacz M，Za??ski A，et al. Impact of combined antiretroviral therapy on metabolic syndrome components in adult people living with HIV：a literature review［J］. Viruses，2022，14（1）：122.
    [4]
    Tsai FJ，Ho MW，Lai CH，et al. Evaluation of oral antiretroviral drugs in mice with metabolic and neurologic complications［J］. Front Pharmacol，2018，9：1004.
    [5]
    Yarchoan R，Klecker RW，Weinhold KJ，et al. Administration of 3''-azido-3''-deoxythymidine，an inhibitor of HTLV-III/LAV replication，to patients with AIDS or AIDS-related complex［J］. Lancet，1986，1（8481）：575-580.
    [6]
    Clumeck N，de Wit S. Update on highly active antiretroviral therapy：progress and strategies［J］. Biomed Pharmacother，2000，54（1）：7-12.
    [7]
    Günthard HF，Saag MS，Benson CA，et al. Antiretroviral drugs for treatment and prevention of HIV infection in adults：2016 recommendations of the international antiviral society-USA panel［J］. JAMA，2016，316（2）：191-210.
    [8]
    Igoudjil A，Massart J，Begriche K，et al. High concentrations of stavudine impair fatty acid oxidation without depleting mitochondrial DNA in cultured rat hepatocytes［J］. Toxicol In Vitro，2008，22（4）：887-898.
    [9]
    Lin H，Stankov MV，Hegermann J，et al. Zidovudine-mediated autophagy inhibition enhances mitochondrial toxicity in muscle cells［J］. Antimicrob Agents Chemother，2018，63（1）：e01443-e01418.
    [10]
    Santos-Llamas A，Monte MJ，Marin JJG，et al. Dysregulation of autophagy in rat liver with mitochondrial DNA depletion induced by the nucleoside analogue zidovudine［J］. Arch Toxicol，2018，92（6）：2109-2118.
    [11]
    Ba?ó M，Morén C，Barroso S，et al. Mitochondrial toxicogenomics for antiretroviral management：HIV post-exposure prophylaxis in uninfected patients［J］. Front Genet，2020，11：497.
    [12]
    Goodpaster BH，Sparks LM. Metabolic flexibility in health and disease［J］. Cell Metab，2017，25（5）：1027-1036.
    [13]
    Morio B，Panthu B，Bassot A，et al. Role of mitochondria in liver metabolic health and diseases［J］. Cell Calcium，2021，94：102336.
    [14]
    Ruocco MR，Avagliano A，Granato G，et al. Metabolic flexibility in melanoma：a potential therapeutic target［J］. Semin Cancer Biol，2019，59：187-207.
    [15]
    Smith RL，Soeters MR，Wüst RCI，et al. Metabolic flexibility as an adaptation to energy resources and requirements in health and disease［J］. Endocr Rev，2018，39（4）：489-517.
    [16]
    Lagathu C，Béréziat V，Gorwood J，et al. Metabolic complications affecting adipose tissue，lipid and glucose metabolism associated with HIV antiretroviral treatment［J］. Expert Opin Drug Saf，2019，18（9）：829-840.
    [17]
    Xiao JQ，Xu J，Shu FR，et al. Effect of Artemisia Argyi Folium ethanolic extract on blood glucose and blood lipids in diabetic mice［J］. J China Pharm Univ（中国药科大学学报），2021，52（1）：71-76.
    [18]
    Soeters MR，Soeters PB，Schooneman MG，et al. Adaptive reciprocity of lipid and glucose metabolism in human short-term starvation［J］. Am J Physiol Endocrinol Metab，2012，303（12）：E1397-E1407.
    [19]
    Gambardella J，Lombardi A，Santulli G. Metabolic flexibility of mitochondria plays a key role in balancing glucose and fatty acid metabolism in the diabetic heart［J］. Diabetes，2020，69（10）：2054-2057.
    [20]
    Tucci S，Alatibi KI，Wehbe Z. Altered metabolic flexibility in inherited metabolic diseases of mitochondrial fatty acid metabolism［J］. Int J Mol Sci，2021，22（7）：3799.
    [21]
    Toma?i? N，Kotarsky H，de Oliveira Figueiredo R，et al. Fasting reveals largely intact systemic lipid mobilization mechanisms in respiratory chain complex III deficient mice［J］. Biochim Biophys Acta Mol Basis Dis，2020，1866（1）：165573.
    [22]
    Qiu XC，Li J，Lv SH，et al. HDAC5 integrates ER stress and fasting signals to regulate hepatic fatty acid oxidation［J］. J Lipid Res，2018，59（2）：330-338.
    [23]
    Bideyan L，Nagari R，Tontonoz P. Hepatic transcriptional responses to fasting and feeding［J］. Genes Dev，2021，35（9/10）：635-657.
    • Related Articles

  • Related Articles

    [1]PAN Kemeng, CHEN Song, GAO Xiangdong, YAO Wenbing. Effects and mechanisms of microRNA-23b on neuronal apoptosis induced by Aβ25-35[J]. Journal of China Pharmaceutical University, 2021, 52(4): 480-486. DOI: 10.11665/j.issn.1000-5048.20210411
    [2]SUN Yan, GAO Xiangdong, CHEN Song. Effect and mechanism of FGF21 on astrocyte damage induced by Aβ25-35[J]. Journal of China Pharmaceutical University, 2019, 50(4): 490-496. DOI: 10.11665/j.issn.1000-5048.20190415
    [3]PENG Xuehan, XIE Wenmin, LI Ji, YU Feng. Comparative investigation of in vitro antitumor activity of Ganoderma lucidum spore oil[J]. Journal of China Pharmaceutical University, 2019, 50(1): 81-86. DOI: 10.11665/j.issn.1000-5048.20190111
    [4]YU Haiyang, CHEN Song, XU Zheng, GAO Xiangdong, YAO Wenbing. Protective effect of fibroin peptides on Aβ25-35-induced injury in SH-SY5Y cells and its mechanism[J]. Journal of China Pharmaceutical University, 2017, 48(5): 609-613. DOI: 10.11665/j.issn.1000-5048.20170517
    [5]WANG Xiao-jie, XINHUA Nabi, SUN Yu. Effects of active peptide extracted from cheese whey on the expression of PPARγ mRNA and NF-κB activity in 3T3-L1 adipocytes[J]. Journal of China Pharmaceutical University, 2012, 43(5): 449-452.
    [6]CHEN Hong, YANG Jie, CUI Wei-xi, WANG Qiang. Effects and mechanism of ursolic acid on lipopolysaccharide-induced THP-1 cells[J]. Journal of China Pharmaceutical University, 2011, 42(5): 447-451.
    [7]XU Ling-jie, LI Cong, ZHANG Mian, DAI Yue, HUANG Fang. Effect of the ethyl acetate extract of Farfarae Flos on inflammatory factors[J]. Journal of China Pharmaceutical University, 2011, 42(1): 64-67.
    [8]Transcription factors as new targets for cancer therapy[J]. Journal of China Pharmaceutical University, 2010, 41(2): 97-103.
    [10]Effect of Nerve Regeneration Factor on GAP-43 and NF-L Gene Expression in Dorsal Roots Ganglia Cell[J]. Journal of China Pharmaceutical University, 2001, (3): 73-76.

Catalog

    Get Citation
    PDF
    XML
    Article views (189) PDF downloads (373) Cited by()
    Turn off MathJax
    Article Contents
    Abstract
    References
    Related Articles

    Copyright © Journal of China Pharmaceutical University苏ICP备12050101号-2

    Address：24 Tongjia Lane, Nanjing City, Jiangsu Province （210009）Tel: 025-83271566E-mail: xuebao@cpu.edu.cn

    Supported by: Beijing Renhe Information Technology Co., Ltd.  Baidu Analytics

    Total visits：365451

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return