Comparative study between adenine and folic acid as optimal models to induce anemia of chronic kidney disease in male rats; an experimental study

Introduction: Anemia of chronic kidney disease (CKD) is a prevalent complication characterized by reduced erythropoiesis and altered iron metabolism. Objectives: This study aims to compare the efficacy of adenine and folic acid in inducing anemia in male rats, providing insights into the underlying mechanisms and potential therapeutic targets. Through a systematic evaluation of hematological parameters and renal function, we assess the suitability of these agents as models for studying CKD-related anemia. Materials and Methods: In this experimental study, 30 male albino Wistar rats were allocated into five groups, each consisting of six rats. Group I served as the healthy control group and received weekly intraperitoneal injections of normal saline. Group II, designated as the adenine model group, was administered a weekly intraperitoneal injection of adenine at a dosage of 250 mg/kg. Group III, also part of the adenine model group, received an intraperitoneal injection of adenine at the same dosage but every two weeks. Group IV represented the folic acid model group, receiving weekly intraperitoneal injections of folic acid at 250 mg/kg, while group V, also part of the folic acid model group, was treated with folic acid at the same dosage every two weeks. Following a 28-day induction period, all rats were sedated and euthanized to facilitate the collection of blood samples for the assessment of kidney function indicators, specifically neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C, across with hematological indicators such as transferrin, hepcidin, and hemoglobin. Results: The results revealed that both folic acid and adenine significantly elevate NGAL, cystatin C, and hepcidin levels in rats, with folic acid showing superior efficacy, particularly at weekly doses. While both treatments effectively reduce hemoglobin and transferrin levels, they do not differ significantly in their overall therapeutic outcomes. Notably, folic acid produced a more pronounced reduction in transferrin compared to adenine. Conclusion: The results demonstrated that both folic acid and adenine significantly affect biomarkers related to kidney function and iron metabolism in rats, with folic acid showing superior efficacy in increasing NGAL, cystatin C, and hepcidin levels. Although both treatments effectively reduced hemoglobin and transferrin levels, they did not differ significantly in their overall impact on hemoglobin reduction.