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

• Published in: Journal of pharmacological and toxicological methods Vol. 68; no. 3; pp. 384 - 393
• Main Authors: Ali, Badreldin H., Al-Salam, Suhail, Al Za'abi, Mohammed, Waly, Mostafa I., Ramkumar, Aishwarya, Beegam, Sumyia, Al-Lawati, Intisar, Adham, Sirin A., Nemmar, Abderrahim
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2013
• Subjects: Acacia; Adenine; Adenine - administration & dosage; Adenine - toxicity; Animal model; Animals; Chronic renal failure; Creatinine - blood; Disease Models, Animal; Dose-Response Relationship, Drug; Glutathione - metabolism; Gum Arabic - pharmacology; Kidney Failure, Chronic - drug therapy; Kidney Failure, Chronic - physiopathology; Male; Mice; Mice, Inbred C57BL; Rats; Rats, Wistar; Severity of Illness Index; Species Specificity; Superoxide Dismutase - metabolism; Urea - metabolism; Adenine; Rats; Animal model; Mice; Chronic renal failure
• ISSN: 1056-8719; 1873-488X
• DOI: 10.1016/j.vascn.2013.05.001

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. 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. When mice and rats were fed adenine (0.75%, w/w), all treated rats survived the treatment, but all treated mice died within 1–2days. The dosage in mice was reduced to 0.3%, w/w, for 4weeks, but again all treated mice died within 3–4days. A further reduction in the dosage in mice to 0.2%, w/w, for 4weeks resulted in no mortality, and produced alterations similar to those observed in rats fed adenine at a dose of 0.75%,w/w, for 4weeks. 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. Our data suggest that mice are more sensitive to adenine than rats, and that a dose of adenine of 0.2%, w/w, for 4weeks in mice is suggested as a model for CRF. In both models, GA (15%, w/v, in the drinking water for 4weeks) given concomitantly with adenine ameliorated the severity of CRF to a similar extent.