Ameliorating Effect of Gemigliptin on Renal Injury in Murine Adriamycin-Induced Nephropathy.
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.
Department of Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea.
Da Rae
0000-0002-7727-5585
DR
Kim
Division of Nephrology, Department of Internal Medicine, Kyung Hee University Hospital, Seoul, Republic of Korea.
Shin Yeong
SY
Lee
Division of Nephrology, Department of Internal Medicine, Kyung Hee University Hospital, Seoul, Republic of Korea.
Jin Sug
JS
Kim
Department of Nephrology, Kyung Hee University School of Medicine, Seoul, Republic of Korea; Division of Nephrology, Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea.
Yang Gyun
YG
Kim
Department of Nephrology, Kyung Hee University School of Medicine, Seoul, Republic of Korea; Division of Nephrology, Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea.
Ju-Young
JY
Moon
Department of Nephrology, Kyung Hee University School of Medicine, Seoul, Republic of Korea; Division of Nephrology, Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea.
Sang Ho
0000-0001-9915-6221
SH
Lee
Division of Nephrology, Department of Internal Medicine, Kyung Hee University Hospital, Seoul, Republic of Korea; Department of Nephrology, Kyung Hee University School of Medicine, Seoul, Republic of Korea.
Tae Won
TW
Lee
Division of Nephrology, Department of Internal Medicine, Kyung Hee University Hospital, Seoul, Republic of Korea; Department of Nephrology, Kyung Hee University School of Medicine, Seoul, Republic of Korea.
Chun Gyoo
CG
Ihm
Division of Nephrology, Department of Internal Medicine, Kyung Hee University Hospital, Seoul, Republic of Korea; Department of Nephrology, Kyung Hee University School of Medicine, Seoul, Republic of Korea.
Kyung Hwan
0000-0003-1492-8021
KH
Jeong
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000633:toxicity; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D010881:Piperidones / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D012097:Repressor Proteins / Q000096:biosynthesis; D025721:WT1 Proteins
C534891:LC15-0444; D008565:Membrane Proteins; D010881:Piperidones; D011743:Pyrimidines; D012097:Repressor Proteins; D025721:WT1 Proteins; C000602896:WT1 protein, mouse; C113267:nephrin; D004317:Doxorubicin