New model for adenine-induced chronic renal failure in mice, and the effect of gum acacia treatment thereon: Comparison with rats

Introduction: This study aimed at comparing the effects of feeding mice and rats with adenine to induce a state of chronic renal failure (CRF), and to assess the effect of treatment with gum acacia (GA) thereon. Methods: We compared the outcome, in mice, of feeding adenine at three different doses (0.75%, 0.3%, and 0.2%, w/w). Biochemical and histopathological studies were conducted in plasma, urine and renal homogenates from both species. Results: When mice and rats were fed adenine (0.75%, w/w), all treated rats survived the treatment, but all treated mice died within 1-2. days. The dosage in mice was reduced to 0.3%, w/w, for 4. weeks, but again all treated mice died within 3-4. days. A further reduction in the dosage in mice to 0.2%, w/w, for 4. weeks resulted in no mortality, and produced alterations similar to those observed in rats fed adenine at a dose of 0.75%,w/w, for 4. weeks. Plasma creatinine, urea and urinary protein were significantly increased (P< 0.001) in adenine-treated mice and rats, and this action was incompletely, but significantly (P< 0.05), reversed by GA. Adenine significantly (P< 0.001) reduced superoxide dismutase (SOD) activity and reduced glutathione (GSH) concentration in renal homogenates from both species, and these reductions were significantly (P< 0.05) ameliorated by GA. Discussion: Our data suggest that mice are more sensitive to adenine than rats, and that a dose of adenine of 0.2%, w/w, for 4. weeks in mice is suggested as a model for CRF. In both models, GA (15%, w/v, in the drinking water for 4. weeks) given concomitantly with adenine ameliorated the severity of CRF to a similar extent.