Saxagliptin Attenuates Diabetic Nephropathy with Suppressing Oxidative Stress by Inhibiting AGEs-RAGE Axis in Streptozotocin-Induced Diabetic Rats

Ye Feng; Chengjiang Li; Yuehuan Liu; Long Zhang; Zhe Zhang

doi:doi:10.11648/j.ajim.20180606.13

| Peer-Reviewed |

Saxagliptin Attenuates Diabetic Nephropathy with Suppressing Oxidative Stress by Inhibiting AGEs-RAGE Axis in Streptozotocin-Induced Diabetic Rats

Ye Feng, Chengjiang Li, Yuehuan Liu, Long Zhang, Zhe Zhang

Received: 16 September 2018 Accepted: 11 October 2018 Published: 5 November 2018

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Abstract

As a dipeptidyl peptidase-4 (DPP-4) inhibitor used in diabetes mellitus (DM) therapy, saxagliptin (Saxa) has been reported an additional protective benefit of diabetic nephropathy (DN), which might be independent of its glucose-lowering effect. However, the mechanism is not fully understood. In this study, STZ-induced DM rat model received a placebo or Saxa (10mg or 20mg/kg, 8-10 rats in each group). Blood glucose, serum lipid, creatinine, blood urea nitrogen, as well as urine protein and albumin concentration, were examined. Gene expression and protein level of advanced glycation end products (AGEs) and their receptor (RAGE) were also tested. Moreover, markers for oxidative stress and antioxidant ability were determined. The results showed moderate albuminuria in diabetic rats was attenuated after Saxa treatment, consistent with morphological improvement supported by histological analysis. Both AGEs and RAGE levels were elevated in DM group but reduced after Saxa administration. Furthermore, the level of malondialdehyde (MAD), Caspase 3, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in kidney were much lower in Saxa group compared with DM group, indicating the oxidation and apoptosis in DM were ameliorated by Saxa. On the other hand, markers of antioxidation such as total antioxidation capability (TAOC), glutathione peroxidase (GSH-PX), and superoxide dismutase (SOD), had a relevant increase, suggesting enhanced antioxidation in the kidney. In conclusion, these findings show that Saxa possesses anti-oxidative activity to ameliorate diabetic renal damage, which is related to the regulation of the AGEs-RAGE axis.

DOI	10.11648/j.ajim.20180606.13
Published in	American Journal of Internal Medicine (Volume 6, Issue 6, November 2018)
Page(s)	161-169
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Dipeptidyl Peptidase-4 Inhibitor, Diabetes Mellitus, Advanced Glycation End Products, AGE Receptor, Oxidative Stress

References

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APA Style

Ye Feng, Chengjiang Li, Yuehuan Liu, Long Zhang, Zhe Zhang. (2018). Saxagliptin Attenuates Diabetic Nephropathy with Suppressing Oxidative Stress by Inhibiting AGEs-RAGE Axis in Streptozotocin-Induced Diabetic Rats. American Journal of Internal Medicine, 6(6), 161-169. https://doi.org/10.11648/j.ajim.20180606.13

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ACS Style

Ye Feng; Chengjiang Li; Yuehuan Liu; Long Zhang; Zhe Zhang. Saxagliptin Attenuates Diabetic Nephropathy with Suppressing Oxidative Stress by Inhibiting AGEs-RAGE Axis in Streptozotocin-Induced Diabetic Rats. Am. J. Intern. Med. 2018, 6(6), 161-169. doi: 10.11648/j.ajim.20180606.13

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AMA Style

Ye Feng, Chengjiang Li, Yuehuan Liu, Long Zhang, Zhe Zhang. Saxagliptin Attenuates Diabetic Nephropathy with Suppressing Oxidative Stress by Inhibiting AGEs-RAGE Axis in Streptozotocin-Induced Diabetic Rats. Am J Intern Med. 2018;6(6):161-169. doi: 10.11648/j.ajim.20180606.13

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@article{10.11648/j.ajim.20180606.13,
  author = {Ye Feng and Chengjiang Li and Yuehuan Liu and Long Zhang and Zhe Zhang},
  title = {Saxagliptin Attenuates Diabetic Nephropathy with Suppressing Oxidative Stress by Inhibiting AGEs-RAGE Axis in Streptozotocin-Induced Diabetic Rats},
  journal = {American Journal of Internal Medicine},
  volume = {6},
  number = {6},
  pages = {161-169},
  doi = {10.11648/j.ajim.20180606.13},
  url = {https://doi.org/10.11648/j.ajim.20180606.13},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajim.20180606.13},
  abstract = {As a dipeptidyl peptidase-4 (DPP-4) inhibitor used in diabetes mellitus (DM) therapy, saxagliptin (Saxa) has been reported an additional protective benefit of diabetic nephropathy (DN), which might be independent of its glucose-lowering effect. However, the mechanism is not fully understood. In this study, STZ-induced DM rat model received a placebo or Saxa (10mg or 20mg/kg, 8-10 rats in each group). Blood glucose, serum lipid, creatinine, blood urea nitrogen, as well as urine protein and albumin concentration, were examined. Gene expression and protein level of advanced glycation end products (AGEs) and their receptor (RAGE) were also tested. Moreover, markers for oxidative stress and antioxidant ability were determined. The results showed moderate albuminuria in diabetic rats was attenuated after Saxa treatment, consistent with morphological improvement supported by histological analysis. Both AGEs and RAGE levels were elevated in DM group but reduced after Saxa administration. Furthermore, the level of malondialdehyde (MAD), Caspase 3, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in kidney were much lower in Saxa group compared with DM group, indicating the oxidation and apoptosis in DM were ameliorated by Saxa. On the other hand, markers of antioxidation such as total antioxidation capability (TAOC), glutathione peroxidase (GSH-PX), and superoxide dismutase (SOD), had a relevant increase, suggesting enhanced antioxidation in the kidney. In conclusion, these findings show that Saxa possesses anti-oxidative activity to ameliorate diabetic renal damage, which is related to the regulation of the AGEs-RAGE axis.},
 year = {2018}
}

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TY  - JOUR
T1  - Saxagliptin Attenuates Diabetic Nephropathy with Suppressing Oxidative Stress by Inhibiting AGEs-RAGE Axis in Streptozotocin-Induced Diabetic Rats
AU  - Ye Feng
AU  - Chengjiang Li
AU  - Yuehuan Liu
AU  - Long Zhang
AU  - Zhe Zhang
Y1  - 2018/11/05
PY  - 2018
N1  - https://doi.org/10.11648/j.ajim.20180606.13
DO  - 10.11648/j.ajim.20180606.13
T2  - American Journal of Internal Medicine
JF  - American Journal of Internal Medicine
JO  - American Journal of Internal Medicine
SP  - 161
EP  - 169
PB  - Science Publishing Group
SN  - 2330-4324
UR  - https://doi.org/10.11648/j.ajim.20180606.13
AB  - As a dipeptidyl peptidase-4 (DPP-4) inhibitor used in diabetes mellitus (DM) therapy, saxagliptin (Saxa) has been reported an additional protective benefit of diabetic nephropathy (DN), which might be independent of its glucose-lowering effect. However, the mechanism is not fully understood. In this study, STZ-induced DM rat model received a placebo or Saxa (10mg or 20mg/kg, 8-10 rats in each group). Blood glucose, serum lipid, creatinine, blood urea nitrogen, as well as urine protein and albumin concentration, were examined. Gene expression and protein level of advanced glycation end products (AGEs) and their receptor (RAGE) were also tested. Moreover, markers for oxidative stress and antioxidant ability were determined. The results showed moderate albuminuria in diabetic rats was attenuated after Saxa treatment, consistent with morphological improvement supported by histological analysis. Both AGEs and RAGE levels were elevated in DM group but reduced after Saxa administration. Furthermore, the level of malondialdehyde (MAD), Caspase 3, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in kidney were much lower in Saxa group compared with DM group, indicating the oxidation and apoptosis in DM were ameliorated by Saxa. On the other hand, markers of antioxidation such as total antioxidation capability (TAOC), glutathione peroxidase (GSH-PX), and superoxide dismutase (SOD), had a relevant increase, suggesting enhanced antioxidation in the kidney. In conclusion, these findings show that Saxa possesses anti-oxidative activity to ameliorate diabetic renal damage, which is related to the regulation of the AGEs-RAGE axis.
VL  - 6
IS  - 6
ER  -

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Author Information

Ye Feng

Department of Endocrinology and Metabolism Disease, the First Affiliated Hospital, Zhejiang University, Hangzhou, China
Chengjiang Li

Department of Endocrinology and Metabolism Disease, the First Affiliated Hospital, Zhejiang University, Hangzhou, China
Yuehuan Liu

Zhejiang Center of Laboratory Animals, Zhangjiang Academy of Medical Sciences, Hangzhou, China
Long Zhang

Department of Endocrinology, Ningbo Medical Treatment Center Lihuili Hospital, Ningbo, China
Zhe Zhang

Department of Endocrinology and Metabolism Disease, the First Affiliated Hospital, Zhejiang University, Hangzhou, China

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APA Style

Ye Feng, Chengjiang Li, Yuehuan Liu, Long Zhang, Zhe Zhang. (2018). Saxagliptin Attenuates Diabetic Nephropathy with Suppressing Oxidative Stress by Inhibiting AGEs-RAGE Axis in Streptozotocin-Induced Diabetic Rats. American Journal of Internal Medicine, 6(6), 161-169. https://doi.org/10.11648/j.ajim.20180606.13

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ACS Style

Ye Feng; Chengjiang Li; Yuehuan Liu; Long Zhang; Zhe Zhang. Saxagliptin Attenuates Diabetic Nephropathy with Suppressing Oxidative Stress by Inhibiting AGEs-RAGE Axis in Streptozotocin-Induced Diabetic Rats. Am. J. Intern. Med. 2018, 6(6), 161-169. doi: 10.11648/j.ajim.20180606.13

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AMA Style

Ye Feng, Chengjiang Li, Yuehuan Liu, Long Zhang, Zhe Zhang. Saxagliptin Attenuates Diabetic Nephropathy with Suppressing Oxidative Stress by Inhibiting AGEs-RAGE Axis in Streptozotocin-Induced Diabetic Rats. Am J Intern Med. 2018;6(6):161-169. doi: 10.11648/j.ajim.20180606.13

Copy | Download

@article{10.11648/j.ajim.20180606.13,
  author = {Ye Feng and Chengjiang Li and Yuehuan Liu and Long Zhang and Zhe Zhang},
  title = {Saxagliptin Attenuates Diabetic Nephropathy with Suppressing Oxidative Stress by Inhibiting AGEs-RAGE Axis in Streptozotocin-Induced Diabetic Rats},
  journal = {American Journal of Internal Medicine},
  volume = {6},
  number = {6},
  pages = {161-169},
  doi = {10.11648/j.ajim.20180606.13},
  url = {https://doi.org/10.11648/j.ajim.20180606.13},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajim.20180606.13},
  abstract = {As a dipeptidyl peptidase-4 (DPP-4) inhibitor used in diabetes mellitus (DM) therapy, saxagliptin (Saxa) has been reported an additional protective benefit of diabetic nephropathy (DN), which might be independent of its glucose-lowering effect. However, the mechanism is not fully understood. In this study, STZ-induced DM rat model received a placebo or Saxa (10mg or 20mg/kg, 8-10 rats in each group). Blood glucose, serum lipid, creatinine, blood urea nitrogen, as well as urine protein and albumin concentration, were examined. Gene expression and protein level of advanced glycation end products (AGEs) and their receptor (RAGE) were also tested. Moreover, markers for oxidative stress and antioxidant ability were determined. The results showed moderate albuminuria in diabetic rats was attenuated after Saxa treatment, consistent with morphological improvement supported by histological analysis. Both AGEs and RAGE levels were elevated in DM group but reduced after Saxa administration. Furthermore, the level of malondialdehyde (MAD), Caspase 3, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in kidney were much lower in Saxa group compared with DM group, indicating the oxidation and apoptosis in DM were ameliorated by Saxa. On the other hand, markers of antioxidation such as total antioxidation capability (TAOC), glutathione peroxidase (GSH-PX), and superoxide dismutase (SOD), had a relevant increase, suggesting enhanced antioxidation in the kidney. In conclusion, these findings show that Saxa possesses anti-oxidative activity to ameliorate diabetic renal damage, which is related to the regulation of the AGEs-RAGE axis.},
 year = {2018}
}

Copy | Download

TY  - JOUR
T1  - Saxagliptin Attenuates Diabetic Nephropathy with Suppressing Oxidative Stress by Inhibiting AGEs-RAGE Axis in Streptozotocin-Induced Diabetic Rats
AU  - Ye Feng
AU  - Chengjiang Li
AU  - Yuehuan Liu
AU  - Long Zhang
AU  - Zhe Zhang
Y1  - 2018/11/05
PY  - 2018
N1  - https://doi.org/10.11648/j.ajim.20180606.13
DO  - 10.11648/j.ajim.20180606.13
T2  - American Journal of Internal Medicine
JF  - American Journal of Internal Medicine
JO  - American Journal of Internal Medicine
SP  - 161
EP  - 169
PB  - Science Publishing Group
SN  - 2330-4324
UR  - https://doi.org/10.11648/j.ajim.20180606.13
AB  - As a dipeptidyl peptidase-4 (DPP-4) inhibitor used in diabetes mellitus (DM) therapy, saxagliptin (Saxa) has been reported an additional protective benefit of diabetic nephropathy (DN), which might be independent of its glucose-lowering effect. However, the mechanism is not fully understood. In this study, STZ-induced DM rat model received a placebo or Saxa (10mg or 20mg/kg, 8-10 rats in each group). Blood glucose, serum lipid, creatinine, blood urea nitrogen, as well as urine protein and albumin concentration, were examined. Gene expression and protein level of advanced glycation end products (AGEs) and their receptor (RAGE) were also tested. Moreover, markers for oxidative stress and antioxidant ability were determined. The results showed moderate albuminuria in diabetic rats was attenuated after Saxa treatment, consistent with morphological improvement supported by histological analysis. Both AGEs and RAGE levels were elevated in DM group but reduced after Saxa administration. Furthermore, the level of malondialdehyde (MAD), Caspase 3, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in kidney were much lower in Saxa group compared with DM group, indicating the oxidation and apoptosis in DM were ameliorated by Saxa. On the other hand, markers of antioxidation such as total antioxidation capability (TAOC), glutathione peroxidase (GSH-PX), and superoxide dismutase (SOD), had a relevant increase, suggesting enhanced antioxidation in the kidney. In conclusion, these findings show that Saxa possesses anti-oxidative activity to ameliorate diabetic renal damage, which is related to the regulation of the AGEs-RAGE axis.
VL  - 6
IS  - 6
ER  -

Copy | Download