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Original Article

The Acupuncture 2015; 32(3): 41-51

Published online September 20, 2015

https://doi.org/10.13045/acupunct.2015037

© Korean Acupuncture & Moxibustion Medicine Society

태충·삼음교의 침 자극이 Streptozotocin으로 유발된 당뇨쥐의 신장 손상에 미치는 영향

이초인, 이현종, 이윤규, 임성철, 김재수*

대구한의대학교 한의과대학 침구경혈학교실

Received: July 31, 2015; Revised: September 2, 2015; Accepted: September 9, 2015

The Effects of LR3 and SP6 Acupuncture on Renal Damage in Streptozotocin-induced Diabetic Mice

Cho In Lee, Hyun Jong Lee, Yun Kyu Lee, Seong Chul Lim and Jae Soo Kim*

Author Info. +

Department of Acupuncture & Moxibustion, Meridian & Acupoint, College of Oriental Medicine, Daegu Haany University

Correspondence to : *Department of Acupuncture & Moxibustion, Medicine, Daegu Oriental Hospital of Daegu Haany University, 136, Sincheondong-ro, Suseong-gu, Daegu, 42158, Republic of Korea
Tel : +82-53-770-2112 E-mail : jaice@daum.net

Received: July 31, 2015; Revised: September 2, 2015; Accepted: September 9, 2015

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Go to

Objectives : This study was performed to investigate the effects of LR3 and SP6 acupuncture on renal damage in streptozotocin(STZ)-induced diabetic mice.
Methods : ICR male mice were stabilized for a week and divided into four groups: a normal mice group(N), no-acupuncture diabetic mice group(Control), LR3 acupuncture diabetic mice group(LR3), and SP6 acupuncture diabetic mice group(SP6). Diabetes was experimentally induced by intraperitoneal injection of STZ(150 mg/kg) in citrate buffer(pH 4.5). For two weeks, LR3 and SP6 acupunctures were administered bilaterally at each point once a day. After two weeks, the animals’ weight was measured and they underwent a laparotomy. Serum glucose and blood urea nitrogen(BUN) were measured from the blood taken from the heart. We measured glucose, reactive oxygen species(ROS), peroxynitrite(ONOO-) and thiobarbituric acid reactive substances(TBARS) in the kidney and compared expression levels of superoxide dismutases(SOD), glutathione peroxidase(GPx), nuclear factor-kappa B(NF-kB), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase(iNOS) and Interleukin-1 beta(IL-1β).
Results : BUN significantly decreased in LR3, SP6 compared to the control group. LR3 showed significantly decreased glucose compared to the control group. LR3, SP6 significantly decreased in ROS and ONOO- compared to the control group. LR3 significantly decreased in TBARS compared to the control group. SP6 significantly increased in expressions of SOD-1, catalase, and GPx compared to the control group. LR3, SP6 significantly decreased in COX-2 compared to the control group. SP6 significantly decreased in IL-1β compared to the control group.
Conclusions : This study suggests that LR3 acupuncture may be effective in controlling glucose and lipid peroxidation and that SP6 acupuncture may have anti-oxidative and anti-inflammatory effects on renal damage in STZ-induced diabetic mice.

Keywords Streptozotocin; Renal damage; Acupuncture; LR3; SP6

Figures

Go to
Fig. 1.

The concentrations of glucose in the kidney

# : p<0.05 compared to normal group by ANOVA followed by Dunnett’s test.

* : p<0.05 compared to control group by ANOVA followed by Dunnett’s test.


Fig. 2.

The concentrations of ROS, TBARS, ONOO− production in the kidney

(A) reactive oxygen species(ROS). (B) thiobarbituric acid reactive substances(TBARS). (C) peroxynitrite(ONOO−).

### : p<0.01 compared to normal group by ANOVA followed by Dunnett’s test.

* : p<0.05, **: p<0.01, *** : p<0.001 compared to control group by ANOVA followed by Dunnett’s test.


Fig. 3.

The expression of antioxidant enzymes-related protein in the kidney

(A) superoxide dismutase(SOD). (B) catalase. (C) glutathion peroxidase(GPx).

# : p<0.05, ## : p<0.01 compared to normal group by ANOVA followed by Dunnett’s test. *p<0.05,

* : p<0.05, ** : p<0.01, *** : p<0.001 compared to control group by ANOVA followed by Dunnett’s test.


Fig. 4.

The NF-κB p65 expressions in the kidney

# : p<0.05 compared to normal group by ANOVA followed by Dunnett’s test.


Fig. 5.

The expressions inflammation-related protein in the kidney

(A) cyclooxygenase-2(COX-2). (B) inducible nitric oxide synthase(iNOS). (C) Interleukin-1 beta(IL-1β).

# : p<0.05, ## : p<0.01, ### : p<0.01 compared to normal group by ANOVA followed by Dunnett’s test.

** : p<0.01 compared to control group by ANOVA followed by Dunnett’s test.


Fig. 6.

The effects and mechanisms of LR3 and SP6 acupuncture on renal protection against hyperglycemic-induced oxidative stress at the kidney


Tables

Go to

The Body Weight Change, Food and Water Intake

GroupBody weight change(g / 14 days)Food intake(g / day)Water intake(ml / day)
Nornal3.39±0.565.87±0.158.63±0.55
Control0.89±0.32#11.25±0.46## 50.04±1.62##
LR30.85±0.069.55±1.3344.50±3.81
SP60.98±0.2013.14±3.3252.34±2.38

All values were showed mean±SD.

#p<0.05,

##p<0.01 compared to normal group by ANOVA followed by Dunnett’s test.

The Hematological Analyses

Groupglucose(mg/dl)BUN(mg/dl)
Normal94.1±0.727.2±1.0
Control260.7±85.6#93.9±0.8###
LR3151.9±41.488.7±0.4***
SP6289.8±5.286.2±0.6***

All values were showed mean±SD.

#p<0.05,

###p<0.001 compared to normal group by ANOVA followed by Dunnett’s test.

***p<0.001 compared to control group by ANOVA followed by Dunnett’s test.

REFERENCES

Go to
  1. Statistics Korea. Korea National Health and Nutrition Examination Survey Available from : URL: http://kosis.kr/statHtml/statHtml.do?orgId=117&tblId=DT_11702_N102&conn_path=I2.
  2. Statics Korea. Annual report on the cause of death statistics 2013 Available from : URL : http://www.index.go.kr/potal/main/EachDtlPageDetail.do?idx_cd=1012.
  3. Fauci, AS, Braunwald, E, Kasper, DL, Hauser, SL, Longo, DL, and Jameson, JL. Harrison’s principles of internal medicine, 17th edition. Korea: Mc Graw Hill Medical; 2008. p. 2282-96.
  4. Dronavalli, Suma, Duka, Irena, and Bakris, George L. The pathogenesis of diabetic nephropathy. Nat Rev Endocrinol 2008;4:444-52.
  5. Lee, JJ, Kim, JM, and Kim, YR. Association of diet-related quality of life with dietary regimen practice, health-related quality of life, and gastrointestinal symptoms in end-stage renal disease patients with hemodialysis. Korean J Nutr 2013;46:137-46.
  6. Kim, MK. Pathophysiology of diabetic nephropathy. Diabetes Metab J 2013;14:15-8.
  7. Kim, EH, Hwang, DY, and Lee, EY. Effects of acupuncture on nNOS-positive neurons in cerebrocortex of streptozotocin-induced diabetic rats. The Acupuncture 2001;18:155-63.
  8. Park, HJ, and Kim, JS. Effects of SP and GV acupuncture on the STZ-treated rats for induction of diabetes. Korean J Microscopy 2006;36:279-89.
  9. Kim, EH Effects of manual acupuncture and herb-acupuncture on cell proliferation of hippocampus in streptozotocin-induced diabetes rat. [dissertation]. Chung Cheong Province: Se-myung University; 2003. Korean
  10. Lee, KY, and Lee, EY. Effects of acupuncture on NADPH-d-positive neurons in cerebrocortex of streptozotocin-induced diabetic rats. Korean J Acupunct 2001;18:138-40.
  11. Hur, KW, Kang, SG, and Kim, YS. A study on serum glucose levels and the pancreatic beta-cell protective effect of acupuncture on sterpetozotocin-treated rats by subcutaneous implantation of osmotic pump. The Acupuncture 2007;24:115-24.
  12. Lee, JM, and Lee, SH. Effects of (CV) and (BL) acupuncture on serum glucose concentration and lipid composition in high fat diet induced diabetic rat. Korean J Acupunct 2004;21:95-102.
  13. Yu, YP, Ju, WP, Li, ZG, Wang, DZ, Wang, YC, and Xie, AM. Acupuncture inhibits oxidative stress and rotational behavior in 6-hydroxydopamine lesioned rat. Brain Res 2010;1336:58-65.
  14. Kang, JM, Park, HJ, and Choi, YG. Acupuncture inhibits microglial activation and inflammatory events in the MPTP-induced mouse model. Brain Res 2007;1131:211-9.
  15. Kang, DH, Yun, YC, Kim, JS, Kim, WJ, and Na, CS. The effect of LR acupuncture on blood pressure and C-fos expression in hypertensive rat induced by 2K1C. Korean J Acupunct 2002;19:47-57.
  16. Song, JK, Lee, BR, Yang, GY, Jeon, JH, and Yim, YK. Anti-oxidative and immune-regulative effects of electro-acupuncture at SP in aged rats. Korean J Acupunct 2010;27:87-106.
  17. Park, CH, Yoon, YC, and Na, CS. Neurologic study of SP acupuncture on bladder parasympathetic nerve, tibial nervve and blood pressure in rats. The Acupuncture 2002;19:175-88.
  18. Koo, ST, Kim, SK, and Kim, EH. ACupuncture point locations for experimental animal studies in rats and mice. Korean J Acupunct 2010;27:67-78.
  19. Mihara, M, and Uchiyama, M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem 1978;86:271-8.
  20. Ziyadeh, FN, and Wolf, G. Pathogenesis of the podocytopathy and proteinuria in diabetic glomerulopathy. Curr Diabetes Rev 2008;4:39-45.
  21. Remuzzi, G, Perico, N, Macia, M, and Puggenenti, P. The role of renin-angiotensin-aldosterone system in the progression of chronic kidney disease. Kidney Int Suppl 2005;68:S57-65.
  22. Kalia, K, Sharma, S, and Mistry, K. Non-enzymatic glycosylation of immunoglobulins in diabetic nephropathy. Clinica Chinica Acta 2004;347:169-76.
  23. Shimoike, T, Inoguchi, T, Umeda, F, Nawata, H, Kawano, K, and Ochi, H. The meaning of serum levels of advanced glycosylation end products in diabetic nephropathy. Metabolism 2000;49:1030-5.
  24. Evcimen, ND, and King, GL. The role of protein kinase C activation and the vascular complications of diabetes. Pharmacol Res 2007;55:498-510.
  25. Ramana, KV, Chandra, D, Srivastava, S, Bhatnagar, A, and Srivastava, SK. Nitric oxide regulates the polyol pathway of glucose metabolism in vascular smooth muscle cells. FASEB J 2003;17:417-25.
  26. Jeong, HC, and Jeong, JC. Effects of on renal function, oxidative stress and polyol pathway in diabetic nephropathy rats. KJOMPP 2007;21:671-8.
  27. Kim, SS, and Son, SM. Oxidative stress and cell dysfunction in diabetes : role of ROS produced by mitochondria and NAD(P)H oxidase. Diabetes Metab J 2008;32:389-98.
  28. Lim, DG. Oxidative stress: reactive oxygen species and nitric oxide. KJCCM 2004;19:81-5.
  29. Kim, BH, and Son, SM. Mechanism of developing diabetic vascular complication by oxidative stress. Endocrinol Metab 2006;21:448-59.
  30. Schoonbroodt, S, and Pette, J. Oxidative stress interference with the nuclear factorκB activation pathways. Biochem Pharmacol 2000;60:1075-81.
  31. Elmarakby, AA. Sullivan JC. Relationship between oxidative stress and inflammatory cytokines in diabetic nephropathy. Cardiovasc Ther 2012;30:49-59.
  32. Jang, TS, Jung, HC, and Ryu, BH. A comparative study on the symptoms and complications between diabetes-mellitus and . Korean J Orient Int Med 1985;2:61-9.

Article

Original Article

The Acupuncture 2015; 32(3): 41-51

Published online September 20, 2015 https://doi.org/10.13045/acupunct.2015037

Copyright © Korean Acupuncture & Moxibustion Medicine Society.

태충·삼음교의 침 자극이 Streptozotocin으로 유발된 당뇨쥐의 신장 손상에 미치는 영향

이초인, 이현종, 이윤규, 임성철, 김재수*

대구한의대학교 한의과대학 침구경혈학교실

Received: July 31, 2015; Revised: September 2, 2015; Accepted: September 9, 2015

The Effects of LR3 and SP6 Acupuncture on Renal Damage in Streptozotocin-induced Diabetic Mice

Cho In Lee, Hyun Jong Lee, Yun Kyu Lee, Seong Chul Lim and Jae Soo Kim*

Department of Acupuncture & Moxibustion, Meridian & Acupoint, College of Oriental Medicine, Daegu Haany University

Correspondence to:*Department of Acupuncture & Moxibustion, Medicine, Daegu Oriental Hospital of Daegu Haany University, 136, Sincheondong-ro, Suseong-gu, Daegu, 42158, Republic of Korea
Tel : +82-53-770-2112 E-mail : jaice@daum.net

Received: July 31, 2015; Revised: September 2, 2015; Accepted: September 9, 2015

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objectives : This study was performed to investigate the effects of LR3 and SP6 acupuncture on renal damage in streptozotocin(STZ)-induced diabetic mice.
Methods : ICR male mice were stabilized for a week and divided into four groups: a normal mice group(N), no-acupuncture diabetic mice group(Control), LR3 acupuncture diabetic mice group(LR3), and SP6 acupuncture diabetic mice group(SP6). Diabetes was experimentally induced by intraperitoneal injection of STZ(150 mg/kg) in citrate buffer(pH 4.5). For two weeks, LR3 and SP6 acupunctures were administered bilaterally at each point once a day. After two weeks, the animals’ weight was measured and they underwent a laparotomy. Serum glucose and blood urea nitrogen(BUN) were measured from the blood taken from the heart. We measured glucose, reactive oxygen species(ROS), peroxynitrite(ONOO-) and thiobarbituric acid reactive substances(TBARS) in the kidney and compared expression levels of superoxide dismutases(SOD), glutathione peroxidase(GPx), nuclear factor-kappa B(NF-kB), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase(iNOS) and Interleukin-1 beta(IL-1β).
Results : BUN significantly decreased in LR3, SP6 compared to the control group. LR3 showed significantly decreased glucose compared to the control group. LR3, SP6 significantly decreased in ROS and ONOO- compared to the control group. LR3 significantly decreased in TBARS compared to the control group. SP6 significantly increased in expressions of SOD-1, catalase, and GPx compared to the control group. LR3, SP6 significantly decreased in COX-2 compared to the control group. SP6 significantly decreased in IL-1β compared to the control group.
Conclusions : This study suggests that LR3 acupuncture may be effective in controlling glucose and lipid peroxidation and that SP6 acupuncture may have anti-oxidative and anti-inflammatory effects on renal damage in STZ-induced diabetic mice.

Keywords: Streptozotocin, Renal damage, Acupuncture, LR3, SP6

Fig 1.

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Figure 1.

The concentrations of glucose in the kidney

# : p<0.05 compared to normal group by ANOVA followed by Dunnett’s test.

* : p<0.05 compared to control group by ANOVA followed by Dunnett’s test.

Journal of Acupuncture Research 2015; 32: 41-51https://doi.org/10.13045/acupunct.2015037

Fig 2.

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Figure 2.

The concentrations of ROS, TBARS, ONOO− production in the kidney

(A) reactive oxygen species(ROS). (B) thiobarbituric acid reactive substances(TBARS). (C) peroxynitrite(ONOO−).

### : p<0.01 compared to normal group by ANOVA followed by Dunnett’s test.

* : p<0.05, **: p<0.01, *** : p<0.001 compared to control group by ANOVA followed by Dunnett’s test.

Journal of Acupuncture Research 2015; 32: 41-51https://doi.org/10.13045/acupunct.2015037

Fig 3.

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Figure 3.

The expression of antioxidant enzymes-related protein in the kidney

(A) superoxide dismutase(SOD). (B) catalase. (C) glutathion peroxidase(GPx).

# : p<0.05, ## : p<0.01 compared to normal group by ANOVA followed by Dunnett’s test. *p<0.05,

* : p<0.05, ** : p<0.01, *** : p<0.001 compared to control group by ANOVA followed by Dunnett’s test.

Journal of Acupuncture Research 2015; 32: 41-51https://doi.org/10.13045/acupunct.2015037

Fig 4.

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Figure 4.

The NF-κB p65 expressions in the kidney

# : p<0.05 compared to normal group by ANOVA followed by Dunnett’s test.

Journal of Acupuncture Research 2015; 32: 41-51https://doi.org/10.13045/acupunct.2015037

Fig 5.

Download
Figure 5.

The expressions inflammation-related protein in the kidney

(A) cyclooxygenase-2(COX-2). (B) inducible nitric oxide synthase(iNOS). (C) Interleukin-1 beta(IL-1β).

# : p<0.05, ## : p<0.01, ### : p<0.01 compared to normal group by ANOVA followed by Dunnett’s test.

** : p<0.01 compared to control group by ANOVA followed by Dunnett’s test.

Journal of Acupuncture Research 2015; 32: 41-51https://doi.org/10.13045/acupunct.2015037

Fig 6.

Download
Figure 6.

The effects and mechanisms of LR3 and SP6 acupuncture on renal protection against hyperglycemic-induced oxidative stress at the kidney

Journal of Acupuncture Research 2015; 32: 41-51https://doi.org/10.13045/acupunct.2015037

Table 1 . The Body Weight Change, Food and Water Intake.

GroupBody weight change(g / 14 days)Food intake(g / day)Water intake(ml / day)
Nornal3.39±0.565.87±0.158.63±0.55
Control0.89±0.32#11.25±0.46## 50.04±1.62##
LR30.85±0.069.55±1.3344.50±3.81
SP60.98±0.2013.14±3.3252.34±2.38

All values were showed mean±SD..

#p<0.05,

##p<0.01 compared to normal group by ANOVA followed by Dunnett’s test.

Table 2 . The Hematological Analyses.

Groupglucose(mg/dl)BUN(mg/dl)
Normal94.1±0.727.2±1.0
Control260.7±85.6#93.9±0.8###
LR3151.9±41.488.7±0.4***
SP6289.8±5.286.2±0.6***

All values were showed mean±SD..

#p<0.05,

###p<0.001 compared to normal group by ANOVA followed by Dunnett’s test.

***p<0.001 compared to control group by ANOVA followed by Dunnett’s test.

References

  1. Statistics Korea. Korea National Health and Nutrition Examination Survey Available from : URL: http://kosis.kr/statHtml/statHtml.do?orgId=117&tblId=DT_11702_N102&conn_path=I2.
  2. Statics Korea. Annual report on the cause of death statistics 2013 Available from : URL : http://www.index.go.kr/potal/main/EachDtlPageDetail.do?idx_cd=1012.
  3. Fauci, AS, Braunwald, E, Kasper, DL, Hauser, SL, Longo, DL, and Jameson, JL. Harrison’s principles of internal medicine, 17th edition. Korea: Mc Graw Hill Medical; 2008. p. 2282-96.
  4. Dronavalli, Suma, Duka, Irena, and Bakris, George L. The pathogenesis of diabetic nephropathy. Nat Rev Endocrinol 2008;4:444-52.
  5. Lee, JJ, Kim, JM, and Kim, YR. Association of diet-related quality of life with dietary regimen practice, health-related quality of life, and gastrointestinal symptoms in end-stage renal disease patients with hemodialysis. Korean J Nutr 2013;46:137-46.
  6. Kim, MK. Pathophysiology of diabetic nephropathy. Diabetes Metab J 2013;14:15-8.
  7. Kim, EH, Hwang, DY, and Lee, EY. Effects of acupuncture on nNOS-positive neurons in cerebrocortex of streptozotocin-induced diabetic rats. The Acupuncture 2001;18:155-63.
  8. Park, HJ, and Kim, JS. Effects of SP and GV acupuncture on the STZ-treated rats for induction of diabetes. Korean J Microscopy 2006;36:279-89.
  9. Kim, EH Effects of manual acupuncture and herb-acupuncture on cell proliferation of hippocampus in streptozotocin-induced diabetes rat. [dissertation]. Chung Cheong Province: Se-myung University; 2003. Korean
  10. Lee, KY, and Lee, EY. Effects of acupuncture on NADPH-d-positive neurons in cerebrocortex of streptozotocin-induced diabetic rats. Korean J Acupunct 2001;18:138-40.
  11. Hur, KW, Kang, SG, and Kim, YS. A study on serum glucose levels and the pancreatic beta-cell protective effect of acupuncture on sterpetozotocin-treated rats by subcutaneous implantation of osmotic pump. The Acupuncture 2007;24:115-24.
  12. Lee, JM, and Lee, SH. Effects of (CV) and (BL) acupuncture on serum glucose concentration and lipid composition in high fat diet induced diabetic rat. Korean J Acupunct 2004;21:95-102.
  13. Yu, YP, Ju, WP, Li, ZG, Wang, DZ, Wang, YC, and Xie, AM. Acupuncture inhibits oxidative stress and rotational behavior in 6-hydroxydopamine lesioned rat. Brain Res 2010;1336:58-65.
  14. Kang, JM, Park, HJ, and Choi, YG. Acupuncture inhibits microglial activation and inflammatory events in the MPTP-induced mouse model. Brain Res 2007;1131:211-9.
  15. Kang, DH, Yun, YC, Kim, JS, Kim, WJ, and Na, CS. The effect of LR acupuncture on blood pressure and C-fos expression in hypertensive rat induced by 2K1C. Korean J Acupunct 2002;19:47-57.
  16. Song, JK, Lee, BR, Yang, GY, Jeon, JH, and Yim, YK. Anti-oxidative and immune-regulative effects of electro-acupuncture at SP in aged rats. Korean J Acupunct 2010;27:87-106.
  17. Park, CH, Yoon, YC, and Na, CS. Neurologic study of SP acupuncture on bladder parasympathetic nerve, tibial nervve and blood pressure in rats. The Acupuncture 2002;19:175-88.
  18. Koo, ST, Kim, SK, and Kim, EH. ACupuncture point locations for experimental animal studies in rats and mice. Korean J Acupunct 2010;27:67-78.
  19. Mihara, M, and Uchiyama, M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem 1978;86:271-8.
  20. Ziyadeh, FN, and Wolf, G. Pathogenesis of the podocytopathy and proteinuria in diabetic glomerulopathy. Curr Diabetes Rev 2008;4:39-45.
  21. Remuzzi, G, Perico, N, Macia, M, and Puggenenti, P. The role of renin-angiotensin-aldosterone system in the progression of chronic kidney disease. Kidney Int Suppl 2005;68:S57-65.
  22. Kalia, K, Sharma, S, and Mistry, K. Non-enzymatic glycosylation of immunoglobulins in diabetic nephropathy. Clinica Chinica Acta 2004;347:169-76.
  23. Shimoike, T, Inoguchi, T, Umeda, F, Nawata, H, Kawano, K, and Ochi, H. The meaning of serum levels of advanced glycosylation end products in diabetic nephropathy. Metabolism 2000;49:1030-5.
  24. Evcimen, ND, and King, GL. The role of protein kinase C activation and the vascular complications of diabetes. Pharmacol Res 2007;55:498-510.
  25. Ramana, KV, Chandra, D, Srivastava, S, Bhatnagar, A, and Srivastava, SK. Nitric oxide regulates the polyol pathway of glucose metabolism in vascular smooth muscle cells. FASEB J 2003;17:417-25.
  26. Jeong, HC, and Jeong, JC. Effects of on renal function, oxidative stress and polyol pathway in diabetic nephropathy rats. KJOMPP 2007;21:671-8.
  27. Kim, SS, and Son, SM. Oxidative stress and cell dysfunction in diabetes : role of ROS produced by mitochondria and NAD(P)H oxidase. Diabetes Metab J 2008;32:389-98.
  28. Lim, DG. Oxidative stress: reactive oxygen species and nitric oxide. KJCCM 2004;19:81-5.
  29. Kim, BH, and Son, SM. Mechanism of developing diabetic vascular complication by oxidative stress. Endocrinol Metab 2006;21:448-59.
  30. Schoonbroodt, S, and Pette, J. Oxidative stress interference with the nuclear factorκB activation pathways. Biochem Pharmacol 2000;60:1075-81.
  31. Elmarakby, AA. Sullivan JC. Relationship between oxidative stress and inflammatory cytokines in diabetic nephropathy. Cardiovasc Ther 2012;30:49-59.
  32. Jang, TS, Jung, HC, and Ryu, BH. A comparative study on the symptoms and complications between diabetes-mellitus and . Korean J Orient Int Med 1985;2:61-9.
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