Ameliorating Effect of Gemigliptin on Renal Injury in Murine Adriamycin-Induced Nephropathy

Abstract

Background. Previous studies have shown the antiapoptotic and anti-inflammatory potential of DPP-IV inhibitor in experimental models of renal injury. We tested whether DPP-IV inhibitor (gemigliptin) ameliorates renal injury by suppressing apoptosis, inflammation, and oxidative stress in mice with adriamycin nephropathy. Methods. Mice were treated with normal saline (control), gemigliptin (GM), adriamycin (ADR), or adriamycin combined with gemigliptin (ADR+GM). Apoptosis, inflammation, and oxidative stress were analyzed via western blotting, real-time PCR, light microscopy, and immunofluorescence. Results. In the ADR+GM group, urine albumin creatinine ratio decreased significantly compared with that in the ADR group on day 15. Glomerulosclerosis index and tubulointerstitial injury index in mice with adriamycin-induced nephropathy decreased after gemigliptin treatment. ADR group showed higher levels of apoptosis, inflammation, and oxidative stress-related molecules compared with the control group. The upregulation of these molecules was significantly reduced by gemigliptin. In the ADR group, the staining intensities of WT-1 and nephrin reduced, but these changes were ameliorated in the ADR+GM group. Conclusion. We demonstrated that gemigliptin ameliorates nephropathy by suppressing apoptosis, inflammation, and oxidative stress in mice administered adriamycin. Our data demonstrate that gemigliptin has renoprotective effects on adriamycin-induced nephropathy.

Protective Effects of Gemigliptin, a Dipeptidyl Peptidase-4 Inhibitor, against Cisplatin-Induced Nephrotoxicity in Mice

“…In agreement with our findings, previous studies have shown that DPP-4 inhibitors have potent antiapoptotic effects in various types of cells [ 10 , 11 , 21 – 24 ]. In addition, DPP-4 inhibitors have been shown to protect against kidney damage induced by nephrotoxic insults, largely via inhibition of apoptosis [ 20 , 25 – 27 ].…”

“…Consistent with our findings, a recent study showed that sitagliptin ameliorated NF- κ B activation and TNF- α production in doxorubicin-induced cardiotoxicity [ 23 ]. Moreover, accumulating evidence suggests that DPP-4 inhibitors exert anti-inflammatory effects in various organs, including the brain [ 21 ], liver [ 22 ], heart [ 24 ], and kidneys [ 25 – 27 ].…”

Activity and selectivity cliffs for DPP‐IV inhibitors: Lessons we can learn from SAR studies and their application to virtual screening

“…For instance, it has been argued whether DPP‐IV must be or must not be administered to cancer patients with diabetes, whereas other studies support the oral administration of DPP‐IV inhibitors in order to either enhance tumor immunotherapy or to slow the growth of different tumors or to suppress colorectal cancer lung metastases in mice . Other studies have demonstrated their therapeutic effects on obesity, neuropathy, and hepatic and renal pathologies. Recent studies have also shown that it is possible to design DPP‐IV inhibitors with dual bioactivity on other targets involved in cardiovascular diseases like ACE or β‐adrenergic receptors …”

Effect of Dipeptidyl Peptidase- 4 (DPP-4) Inhibitor on Biomarkers of Kidney Injury and Vascular Calcification in Diabetic Nephropathy: A Randomized Controlled Trial

“…12 In addition to the glucose-lowering effects of DPP-4 inhibitors and the tissue-protective effects of DPP-4 inhibition have been demonstrated in particular ischemia-reperfusion injury, diabetic kidney disease and CKD. Kim et al 13 reported that gemigliptin treatment led to a reduction in apoptosis, in ammation, and oxidative stress in a murine model of adriamycin-induced nephropathy. Choi et al 14 showed that gemigliptin attenuated cisplatin-induced renal dysfunction in mice.…”