Comparative analysis of inflammatory and oxidative stress indicators in rat models of CKD induced by adenine versus folic acid; an experimental study

Introduction: Chronic kidney disease (CKD) is a progressive condition characterized by inflammation, oxidative stress, and significant renal dysfunction. Animal models are indispensable for studying CKD pathophysiology and testing therapeutic strategies. Among these, adenine and folic acid-induced CKD models are widely used due to their simplicity and reproducibility. Objectives: This study aims to compare inflammatory and oxidative stress indicators in rat models of CKD induced by adenine and folic acid. Materials and Methods: This experimental study was conducted on 30 male Wistar rats at Mustansiriyah University, Iraq, in 2023, to investigate the effects of CKD induced by adenine and folic acid. The rats were divided into five groups, each consisting of six animals, and treated over four weeks with varying dosages of adenine or folic acid weekly and bi-weekly, while a control group received normal saline. Data collection involved anesthetizing the rats and extracting blood for serum analysis. The serum was subsequently used to measure inflammatory markers such as tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6), along with oxidative stress biomarkers like glutathione (GSH) and malondialdehyde (MDA), using enzyme-linked immunosorbent assays (ELISA). Data were compared between groups using statistical tests. Results: This study compared inflammatory and oxidative stress markers in CKD rat models induced by adenine and folic acid, revealing notable differences based on treatment type and frequency. Folic acid, particularly at a weekly dosage, elicited stronger pro-inflammatory effects, significantly increasing TNF-α and IL-6 levels compared to adenine. Weekly folic acid administration also demonstrated a dose-dependent response within its group, with greater effects than bi-weekly dosing. Regarding oxidative stress markers, both folic acid and adenine reduced GSH levels and increased MDA levels compared to controls, but weekly folic acid was the most potent in reducing GSH and increasing MDA. Bi-weekly adenine had the least impact on these markers. Conclusion: This study highlights that both folic acid and adenine induce inflammatory and oxidative stress in CKD rat models, with folic acid, particularly at a weekly dosage, showing a stronger pro-inflammatory and oxidative impact. The findings emphasize the dose-dependent effects of folic acid and its greater potency compared to adenine, offering insights into the differential mechanisms of CKD progression and the importance of treatment frequency and type in experimental models.