Protective Effects of Xanthine Derivatives Against Arsenic Trioxide-Induced Oxidative Stress in Mouse Hepatic and Renal Tissues.
Navid OmidifarAhmad GholamiMansoureh ShokripourMohammad Ali NouraniYounes GhasemiSeyyed Mojtaba MousaviSeyyed Alireza HashemiBagher KhorramAmir Nili AhmadabadiMahintaj DaraPublished in: Drug research (2024)
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.
Keyphrases
- oxidative stress
- diabetic rats
- gene expression
- high glucose
- nitric oxide
- drug induced
- uric acid
- poor prognosis
- dna damage
- drinking water
- dna methylation
- endothelial cells
- heavy metals
- metabolic syndrome
- type diabetes
- real time pcr
- hydrogen peroxide
- ischemia reperfusion injury
- induced apoptosis
- risk assessment
- mass spectrometry
- respiratory failure
- mechanical ventilation
- insulin resistance
- atomic force microscopy
- combination therapy
- signaling pathway
- acute respiratory distress syndrome
- high speed