The renoprotective effect of the dipeptidyl peptidase-4 inhibitor sitagliptin on adenine-induced kidney disease in rats

Aly Abdelrahman, Yousuf Al Suleimani, Mohammed A l Za'abi, Mohammed Ashique, Priyadarsini Manoj, Christina Hartmann, Abderrahim Nemmar, Nicole Schupp, Badreldin Ali

Research output: Contribution to journalArticle

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Abstract

We assessed the effect of treatment with the dipeptidyl peptidase-4 inhibitor, sitagliptin, on adenine-induced chronic kidney disease (CKD). Six equal groups of rats were given either normal food or food mixed with adenine (0.25% w/w for five weeks) to induce CKD. Some of these groups were also simultaneously treated with sitagliptin (2.5 and 10 mg/kg/day, by gavage). Rats given adenine showed elevation of blood pressure, decreased body weight and increased relative kidney weight. Adenine also significantly increased plasma urea, creatinine, cystatin C, liver-type fatty acid–binding protein concentrations and neutrophil gelatinase-associated lipocalin activity by 404%, 354%, 667%, 91% and 281% respectively and reduced plasma α-Klotho by 50%. In addition, adenine significantly increased albumin/creatinine ratio and N-acetyl-β-D-glucosaminidase activity by 3553% and 400% respectively and reduced creatinine clearance by 91%. Adenine feeding also significantly elevated the plasma concentration of inflammatory cytokines (plasma tumor necrosis factor-alpha, interleukin-1beta and transforming growth factor beta-1) and significantly reduced antioxidant indices (catalase, glutathione reductase and superoxide dismutase). Histopathologically, adenine caused renal fibrosis, inflammation and atrophy. When given concomitantly with adenine, sitagliptin ameliorated all the measured adenine-induced physiological and biochemical changes but not the histopathological changes. Sitagliptin (10 mg/kg/day) reduced plasma urea and creatinine by 32% and 25% respectively and increased creatinine clearance by 248%. These findings suggest a renoprotective action of sitagliptin on adenine-induced CKD.

Original languageEnglish
Pages (from-to)667-676
Number of pages10
JournalBiomedicine and Pharmacotherapy
Volume110
DOIs
Publication statusPublished - Feb 1 2019

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Dipeptidyl-Peptidase IV Inhibitors
Kidney Diseases
Adenine
Creatinine
Chronic Renal Insufficiency
Urea
Sitagliptin Phosphate
Kidney
Cystatin C
Hexosaminidases
Food
Glutathione Reductase
Fatty Liver
Interleukin-1beta
Transforming Growth Factor beta
Catalase
Superoxide Dismutase
Atrophy
Albumins
Fibrosis

Keywords

  • Adenine
  • Blood pressure
  • Chronic kidney disease
  • Dipeptidyl peptidase-4 inhibitors
  • Kidney function
  • Sitagliptin

ASJC Scopus subject areas

  • Pharmacology

Cite this

The renoprotective effect of the dipeptidyl peptidase-4 inhibitor sitagliptin on adenine-induced kidney disease in rats. / Abdelrahman, Aly; Al Suleimani, Yousuf; A l Za'abi, Mohammed; Ashique, Mohammed; Manoj, Priyadarsini; Hartmann, Christina; Nemmar, Abderrahim; Schupp, Nicole; Ali, Badreldin.

In: Biomedicine and Pharmacotherapy, Vol. 110, 01.02.2019, p. 667-676.

Research output: Contribution to journalArticle

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abstract = "We assessed the effect of treatment with the dipeptidyl peptidase-4 inhibitor, sitagliptin, on adenine-induced chronic kidney disease (CKD). Six equal groups of rats were given either normal food or food mixed with adenine (0.25{\%} w/w for five weeks) to induce CKD. Some of these groups were also simultaneously treated with sitagliptin (2.5 and 10 mg/kg/day, by gavage). Rats given adenine showed elevation of blood pressure, decreased body weight and increased relative kidney weight. Adenine also significantly increased plasma urea, creatinine, cystatin C, liver-type fatty acid–binding protein concentrations and neutrophil gelatinase-associated lipocalin activity by 404{\%}, 354{\%}, 667{\%}, 91{\%} and 281{\%} respectively and reduced plasma α-Klotho by 50{\%}. In addition, adenine significantly increased albumin/creatinine ratio and N-acetyl-β-D-glucosaminidase activity by 3553{\%} and 400{\%} respectively and reduced creatinine clearance by 91{\%}. Adenine feeding also significantly elevated the plasma concentration of inflammatory cytokines (plasma tumor necrosis factor-alpha, interleukin-1beta and transforming growth factor beta-1) and significantly reduced antioxidant indices (catalase, glutathione reductase and superoxide dismutase). Histopathologically, adenine caused renal fibrosis, inflammation and atrophy. When given concomitantly with adenine, sitagliptin ameliorated all the measured adenine-induced physiological and biochemical changes but not the histopathological changes. Sitagliptin (10 mg/kg/day) reduced plasma urea and creatinine by 32{\%} and 25{\%} respectively and increased creatinine clearance by 248{\%}. These findings suggest a renoprotective action of sitagliptin on adenine-induced CKD.",
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AU - Ashique, Mohammed

AU - Manoj, Priyadarsini

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AU - Nemmar, Abderrahim

AU - Schupp, Nicole

AU - Ali, Badreldin

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