Drug Res (Stuttg) 2024; 74(03): 133-144
DOI: 10.1055/a-2247-5232
Original Article

Protective Effects of Xanthine Derivatives Against Arsenic Trioxide-Induced Oxidative Stress in Mouse Hepatic and Renal Tissues

Navid Omidifar
1   Biotechnology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
2   Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Ahmad Gholami
1   Biotechnology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
3   Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
Mansoureh Shokripour
2   Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Mohammad Ali Nourani
2   Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
4   Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Seyyed Mojtaba Mousavi
5   Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei City, Taiwan
Seyyed Alireza Hashemi
6   Health Policy Research Center, Health Institute, Shiraz University of Medical Sciences, Shiraz, Iran
Bagher Khorram
7   Student Research Committee, School of Nursing and Midwifery, Shiraz University of Medical Sciences, Shiraz, Iran
8   Department of Pharmacology and Toxicology, Medicinal Plants and Natural Products Research Center, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan
Mahintaj Dara
9   Stem Cells and Transgenic Technology Center, Shiraz University of Medical Sciences, Shiraz, Iran
› Author Affiliations


In this study, the protective efficacy of pentoxifylline (PTX) as a xanthine derivative against arsenic trioxide (ATO)-induced kidney and liver damage in mice was investigated. Thirty-six mice were divided into six groups, receiving intraperitoneal injections of saline, ATO, PTX, or a combination for four weeks. Blood samples were analyzed for serum biochemistry, while hepatic tissue underwent examination for histopathological changes and assessment of oxidative stress markers and antioxidant gene expression through Real-Time PCR. ATO exposure significantly increased serum markers (creatinine, ALT, BUN, ALP, AST) and induced histopathological changes in the liver. Moreover, it elevated renal and hepatic nitric oxide (NO) and lipid peroxidation (LPO) levels, and reduced antioxidant enzyme expression (CAT, GSR, GPx, MPO, SOD), total thiol groups (TTGs), and total antioxidant capacity (TAC). Conversely, PTX treatment effectively lowered serum hepatic and renal markers, improved antioxidant markers, and induced histopathological alterations. Notably, PTX did not significantly affect renal and hepatic NO levels. These findings suggest that PTX offers therapeutic potential in mitigating liver and acute kidney injuries induced by various insults, including exposure to ATO.

Publication History

Received: 23 November 2023

Accepted: 15 January 2024

Article published online:
13 February 2024

© 2024. Thieme. All rights reserved.

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