Pyrazinamide enhances lipid peroxidation and antioxidant levels to induce liver injury in rat models through PI3k/Akt inhibition.

Toxicology Research
Yun XuYi Li

Abstract

Pyrazinamide (PZA) is an anti-tuberculosis drug known to causes liver injury. phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signaling protects against liver injury by promoting cellular antioxidant defenses and reducing intracellular reactive oxygen species (ROS) and lipid peroxidation. The regulatory mechanisms and functions of PI3K/Akt signaling during the hepatotoxicity of PZA are however not fully understood. Rats were administered PZA or/and the PI3K activator (740Y-P) for 7 days. The levels of serum parameters were examined via standard enzymatic techniques and the pathological status of the liver was confirmed by H & E staining. The levels of lipid peroxidation and antioxidant production were determined using commercial kits. Liver apoptosis was assessed by TUNEL staining. The expression of apoptosis-related proteins and PI3K/Akt signaling were assessed by western blot analysis. PZA treatment significantly increased serum alanine transaminase, aspartate transaminase, gamma-glutamyl transpeptidase and tall bilirubin leading to liver damage in rats. PZA also facilitated lipid peroxidation and suppressed antioxidant defenses. PZA led to apoptotic induction in rat liver cells through the downregulation of Bcl-2 a...Continue Reading

References

Mar 17, 2004·Cancer Treatment Reviews·Juan Angel Fresno VaraManuel González-Barón
Apr 20, 2012·Expert Review of Anti-infective Therapy·Rannakoe J Lehloenya, Keertan Dheda
Sep 18, 2012·Antioxidants & Redox Signaling·Sergey I Dikalov, David G Harrison
Jun 24, 2014·Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS)·Mohamed E El-BoshyTaibi Ben Hadda
Jul 11, 2014·World Journal of Gastroenterology : WJG·Halina Cichoż-Lach, Agata Michalak
Oct 24, 2014·World Journal of Gastroenterology : WJG·Giuseppe ParadiesGiuseppe Petrosillo
Jan 16, 2015·Redox Biology·Helmut Sies
Feb 6, 2015·Journal of Korean Medical Science·Ina JeongJae-Ho Lee
Apr 29, 2015·Current Drug Targets·Wensheng LiuLixin Zhu
May 1, 2015·Cell Cycle·Kewei Wang
Jul 24, 2015·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Bao-quan SongZhong-chao Han
Sep 27, 2015·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Marco SchitoAlimuddin Zumla
Oct 3, 2015·Current Protein & Peptide Science·Michelle Fidelis Corrêa, João Paulo-dos Santos Fernandes
Oct 17, 2015·Annual Review of Medicine·Ingrid A Mayer, Carlos L Arteaga
Oct 31, 2015·Experimental Cell Research·Rotonya M Carr, Rexford S Ahima
Nov 2, 2015·Advances in Medical Sciences·Moses NjireTianyu Zhang
Mar 22, 2016·Oxidative Medicine and Cellular Longevity·Jixiang ZhangWeiguo Dong
Apr 14, 2016·Journal of Applied Toxicology : JAT·Yun ZhangZhenzhou Jiang
Jun 4, 2016·Toxicological Sciences : an Official Journal of the Society of Toxicology·Hong-Li GuoZhen-Zhou Jiang
Nov 16, 2016·Clinics in Liver Disease·Amina Ibrahim ShehuRaman Venkataramanan
Jan 7, 2017·Journal of Cellular Physiology·Xiliang DuXinwei Li
Jan 7, 2017·The Pediatric Infectious Disease Journal·Yiyuan LiChaomin Wan
Jan 25, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Eleni VergadiChristos Tsatsanis
Feb 23, 2017·Revista brasileira de enfermagem·Fernando MitanoPedro Fredemir Palha
Mar 23, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Jian-Feng XueXiao-Lin Li
May 4, 2017·Seminars in Cancer Biology·Jake S O'DonnellMario Mandala
Jun 14, 2017·Antimicrobial Agents and Chemotherapy·Maxwell T ChirehwaPaolo Denti
Oct 24, 2017·Molecular and Cellular Endocrinology·Xiaoyu LiaoHongting Zheng
Nov 1, 2017·World Journal of Gastroenterology : WJG·Amedeo LonardoLuigi Elio Adinolfi
Nov 22, 2018·The New England Journal of Medicine·Marcus D GoncalvesLewis C Cantley
Jan 18, 2019·Journal of Oral and Maxillofacial Pathology : JOMFP·Kshipra Chandrakant DeshpandeDinesh V Rajput

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