Arsenic-Induced Injury of Mouse Hepatocytes through Lysosome and Mitochondria: An In Vitro Study

被引:7
|
作者
Santra, Amal [1 ,2 ]
Bishnu, Debasree [1 ]
Santra, Suman [3 ]
Ghatak, Subhadip [3 ]
Mukherjee, Partha Sarathi [1 ,2 ]
Dhali, Gopal Krishna [2 ,3 ]
Chowdhury, Abhijit [1 ,2 ,3 ]
机构
[1] JCM Ctr Liver Res & Innovat, Kolkata, India
[2] Liver Fdn, Kolkata, W Bengal, India
[3] Ctr Liver Res, Sch Digest & Liver Dis, Inst Post Grad Med Educ & Res, Kolkata, India
关键词
OXIDATIVE STRESS; CELL-DEATH; MEMBRANE PERMEABILIZATION; PORTAL-HYPERTENSION; LIVER; ACTIVATION; APOPTOSIS; HEPATITIS; FIBROSIS;
D O I
10.1155/2022/1546297
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background and Aims. The cellular mechanism of liver injury related to arsenic toxicity is ill defined. It is thought that oxidative stress and mitochondrial dysfunction may play some role in arsenic-induced liver damage. In this study, we evaluated subcellular events within the primary cultured mouse hepatocytes when exposed to inorganic arsenic. Methods. Primary cultured mouse hepatocytes were treated with 10 mu M arsenic for different time periods. Reactive oxygen species (ROS) formation, functional changes of the lysosome and mitochondria, and mode of hepatocytes death were studied by laser confocal microscopy, fluorescence spectroscopy, and flow cytometry. Expression of proapoptotic member of the BCL-2 family of genes BAX and antiapoptotic BCL-2 mRNA expression were studied by real-time PCR. Cytochrome c expression was studied by Western blotting. Results. Fluorescence spectroscopy as well as flow cytometric analysis revealed that arsenic-induced formation of ROS was time dependent. Confocal microscopy showed initiation of ROS formation from periphery of the hepatocytes at 30 min of arsenic exposure that progressed to central part of the hepatocytes at 3 h of arsenic exposure. The ROS formation was found to be NADPH oxidase (NOX) dependent. This low level of intracellular ROS induced lysosomal membrane permeabilization (LMP) and subsequently released cathepsin B to the cytosol. The LMP further increased intracellular ROS which in turn triggered induction of mitochondrial permeability transition (MPT). Pretreatment of hepatocytes with LMP inhibitor bafilomycin A (BafA) significantly decreased, and LMP inducer chloroquine (ChQ) significantly increased the production of ROS suggesting that LMP preceded enhanced ROS generation in response to arsenic. MPT was accompanied with increase in BAX : BCL2 mRNA ratio resulting in upregulation of caspase 3 and increased hepatocyte apoptosis. Conclusion. Although arsenic-related oxidative liver injury is well established, neither the site of origin of ROS nor the early sequence of events in arsenic toxicity due to ROS is known. We believe that our study provides evidences elucidating the early sequence of events that culminates in the death of the mouse hepatocytes during arsenic exposure.
引用
收藏
页数:12
相关论文
共 50 条
  • [21] Assessing the mechanisms and adjunctive therapy for arsenic-induced liver injury in rats
    Xu, Yuyan
    Zeng, Qibing
    Zhang, Aihua
    ENVIRONMENTAL TOXICOLOGY, 2023, 39 (03) : 1197 - 1209
  • [22] Arsenic-induced oxidative myocardial injury: protective role of arjunolic acid
    Prasenjit Manna
    Mahua Sinha
    Parames C. Sil
    Archives of Toxicology, 2008, 82 : 137 - 149
  • [23] Arsenic-induced myocardial injury: Protective role of Corchorus olitorius leaves
    Das, Anup K.
    Sahu, Ranabir
    Dua, Tarun K.
    Bag, Sujit
    Gangopadhyay, Moumita
    Sinha, Mohit K.
    Dewanjee, Saikat
    FOOD AND CHEMICAL TOXICOLOGY, 2010, 48 (05) : 1210 - 1217
  • [24] Antioxidants in detoxification of arsenic-induced oxidative injury in rabbits: Preliminary results
    Rabbani, G.H. (rabbani@icddrb.org), 1600, Marcel Dekker Inc. (38):
  • [25] Antioxidants in detoxification of arsenic-induced oxidative injury in rabbits: Preliminary results
    Rabbani, GH
    Saha, SK
    Akhtar, M
    Marni, F
    Mitra, AK
    Ahmed, S
    Alauddin, M
    Bhattacharjee, M
    Sultana, S
    Chowdhury, AKA
    JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART A-TOXIC/HAZARDOUS SUBSTANCES & ENVIRONMENTAL ENGINEERING, 2003, 38 (01): : 273 - 287
  • [26] Ameliorative Effects of Caffeic Acid Against Arsenic-Induced Testicular Injury in Mice
    Moghadam, Maryam Dehdashti
    Baghshani, Hasan
    Azadi, Hamideh Ghodrati
    Moosavi, Zahra
    BIOLOGICAL TRACE ELEMENT RESEARCH, 2021, 199 (10) : 3772 - 3780
  • [27] Ameliorative Effects of Caffeic Acid Against Arsenic-Induced Testicular Injury in Mice
    Maryam Dehdashti Moghadam
    Hasan Baghshani
    Hamideh Ghodrati Azadi
    Zahra Moosavi
    Biological Trace Element Research, 2021, 199 : 3772 - 3780
  • [28] Protective effect of curcumin against arsenic-induced apoptosis in murine splenocytes in vitro
    Khan, Saleem
    Vala, Jignesh A.
    Nabi, Showkat U.
    Gupta, Gaurav
    Kumar, Dhirendra
    Telang, Avinash G.
    Malik, J. K.
    JOURNAL OF IMMUNOTOXICOLOGY, 2012, 9 (02) : 148 - 159
  • [29] Effects of tauroursodeoxycholate on arsenic-induced hepatic injury in mice: A comparative transcriptomic analysis
    Zheng, Xiujuan
    Cao, Jianbin
    Wang, He
    Liu, Lele
    Jin, Baiming
    Zhang, Hua
    Li, Mingqi
    Nian, Shijing
    Li, Haonan
    He, Rui
    Wang, Ningning
    Li, Xuying
    Wang, Kewei
    JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY, 2024, 86
  • [30] Hepatoprotective role and antioxidant capacity of selenium on arsenic-induced liver injury in rats
    Messarah, Mahfoud
    Klibet, Fahima
    Boumendjel, Amel
    Abdennour, Cherif
    Bouzerna, Noureddine
    Boulakoud, Mohamed Salah
    El Feki, Abdelfattah
    EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY, 2012, 64 (03) : 167 - 174