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

Badreldin H. Ali, Suhail Al-Salam, Mohammed Al Za'abi, Mostafa I. Waly, Aishwarya Ramkumar, Sumyia Beegam, Intisar Al-Lawati, Sirin A. Adham, Abderrahim Nemmar

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)384-393
Number of pages10
JournalJournal of Pharmacological and Toxicological Methods
Volume68
Issue number3
DOIs
Publication statusPublished - Nov 2013

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Gum Arabic
Adenine
Chronic Kidney Failure
Rats
Plasmas
Kidney
Drinking Water
Superoxide Dismutase
Glutathione
Urea
Creatinine
Urine

Keywords

  • Adenine
  • Animal model
  • Chronic renal failure
  • Mice
  • Rats

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

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

In: Journal of Pharmacological and Toxicological Methods, Vol. 68, No. 3, 11.2013, p. 384-393.

Research output: Contribution to journalArticle

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abstract = "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.",
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AU - Ali, Badreldin H.

AU - Al-Salam, Suhail

AU - Al Za'abi, Mohammed

AU - Waly, Mostafa I.

AU - Ramkumar, Aishwarya

AU - Beegam, Sumyia

AU - Al-Lawati, Intisar

AU - Adham, Sirin A.

AU - Nemmar, Abderrahim

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N2 - 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.

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