Key result
Alogliptin significantly reduced renal fibrosis, as evidenced by decreased a-smooth muscle actin positive area and TGF-b mRNA expression, compared to vehicle in a mouse model of progressive renal fibrosis.
Why the study?
Does alogliptin reduce renal fibrosis and inflammation in a nondiabetic mouse model of progressive renal fibrosis?
Does alogliptin reduce renal fibrosis and inflammation in a nondiabetic mouse model of progressive renal fibrosis?
Alogliptin exerts renoprotective antifibrotic and anti-inflammatory effects in a nondiabetic mouse model of progressive renal fibrosis, suggesting potential therapeutic utility for nondiabetic CKD.
Answers are grounded in this paper and cite their sources.
Caution against clinical use in nondiabetic CKD; leaves open antifibrotic effects of alogliptin for human trials.
Although the effects of dipeptidyl peptidase 4 (DPP-4) inhibitors beyond their hypoglycemic action have been reported, whether these inhibitors have renoprotective effects in nondiabetic chronic kidney disease (CKD) is unclear. We examined the therapeutic effects of DPP-4 inhibition in mice with unilateral ureteral obstruction (UUO), a nondiabetic model of progressive renal fibrosis. After UUO surgery, mice were administered either the DPP-4 inhibitor alogliptin or a vehicle by oral gavage once a day for 10 days. Physiological parameters, degrees of renal fibrosis and inflammation, and molecules related to renal fibrosis and inflammation were then evaluated using sham-operated mice as controls. Positive area of α-smooth muscle actin was significantly smaller and expression of transforming growth factor β messenger RNA was significantly lower in the alogliptin-treated group than in the vehicle-treated group. Renal total collagen content was also significantly lower in the alogliptin-treated group than in the vehicle-treated group. These results suggest that alogliptin exerted renoprotective antifibrotic effects. The positive area of F4/80 was significantly smaller and expression of CD68 messenger RNA was significantly lower in the alogliptin-treated group than in the vehicle-treated group, suggesting an anti-inflammatory action by the DPP-4 inhibitor. Compared to the results for the vehicle-treated group, expression of markers for M1 macrophages tended to be lower in the alogliptin-treated group, and the relative expression of M2 macrophages tended to be higher. These data indicate the various protective effects of DPP-4 inhibition in nondiabetic mice with UUO. DPP-4 inhibitors may therefore be promising therapeutic choices even for nondiabetic CKD patients.
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Uchida et al. (2017) studied Progressive renal fibrosis (unilateral ureteral obstruction model) (n=27). Alogliptin vs. Vehicle (saline) was evaluated on Renal fibrosis (a-smooth muscle actin positive area and TGF-b mRNA expression) (p=<0.01). Alogliptin significantly reduced renal fibrosis, as evidenced by decreased a-smooth muscle actin positive area and TGF-b mRNA expression, compared to vehicle in a mouse model of progressive renal fibrosis.
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