scholarly journals Effects of Dietary Supplementation of α-Lipoic Acid on Early Glomerular Injury in Diabetes Mellitus

2001 ◽  
Vol 12 (1) ◽  
pp. 124-133
Author(s):  
MONA F. MELHEM ◽  
PATRICIA A. CRAVEN ◽  
FREDERICK R. DERUBERTIS

Abstract. Antioxidants, in particular vitamin E (VE), have been reported to protect against diabetic renal injury. α-Lipoic acid (LA) has been found to attenuate diabetic peripheral neuropathy, but its effects on nephropathy have not been examined. In the present study, parameters of glomerular injury were examined in streptozotocin diabetic rats after 2 mo on unsupplemented diets and in diabetic rats that received the lowest daily dose of dietary LA (30 mg/kg body wt), VE (100 IU/kg body wt), or vitamin C (VC; 1 g/kg body wt), which detectably increased the renal cortical content of each antioxidant. Blood glucose values did not differ among the diabetic groups. At 2 mo, inulin clearance, urinary albumin excretion, fractional albumin clearance, glomerular volume, and glomerular content of immunoreactive transforming growth factor-β (TGF-β) and collagen α1 (IV) all were significantly increased in unsupplemented D compared with age-matched nondiabetic controls. With the exception of inulin clearance, LA prevented or significantly attenuated the increase in all of these glomerular parameters in D, as well as the increases in renal tubular cell TGF-β seen in D. At the dose used, VE reduced inulin clearance in D to control levels but failed to alter any of the other indices of glomerular injury or to suppress renal tubular cell TGF-β in D. VC suppressed urinary albumin excretion, fractional albumin clearance, and glomerular volume but not glomerular or tubular TGF-β or glomerular collagen α1 (IV) content. LA but not VE or VC significantly increased renal cortical glutathione content in D. These data indicate that LA is effective in the prevention of early diabetic glomerular injury and suggest that this agent may have advantages over high doses of either VE or VC.

Diabetologia ◽  
1994 ◽  
Vol 37 (1) ◽  
pp. 10-14 ◽  
Author(s):  
A. C. Nieuwenhuijzen Kruseman ◽  
H. A. J. Struijker Boudier ◽  
M. S. P. Huijberts ◽  
B. H. R. Wolffenbuttel ◽  
F. R. L. Crijns ◽  
...  

Diabetologia ◽  
1994 ◽  
Vol 37 (1) ◽  
pp. 10-14 ◽  
Author(s):  
M. S. P. Huijberts ◽  
B. H. R. Wolffenbuttel ◽  
F. R. L. Crijns ◽  
A. C. Nieuwenhuijzen Kruseman ◽  
M. H. A. Bemelmans ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yongjun Zhu ◽  
Hongwang Cui ◽  
Jie Lv ◽  
Haiqin Liang ◽  
Yanping Zheng ◽  
...  

AbstractAbnormal renin-angiotensin system (RAS) activation plays a critical role in the initiation and progression of chronic kidney disease (CKD) by directly mediating renal tubular cell apoptosis. Our previous study showed that necroptosis may play a more important role than apoptosis in mediating renal tubular cell loss in chronic renal injury rats, but the mechanism involved remains unknown. Here, we investigate whether blocking the angiotensin II type 1 receptor (AT1R) and/or angiotensin II type 2 receptor (AT2R) beneficially alleviates renal tubular cell necroptosis and chronic kidney injury. In an angiotensin II (Ang II)-induced renal injury mouse model, we found that blocking AT1R and AT2R effectively mitigates Ang II-induced increases in necroptotic tubular epithelial cell percentages, necroptosis-related RIP3 and MLKL protein expression, serum creatinine and blood urea nitrogen levels, and tubular damage scores. Furthermore, inhibition of AT1R and AT2R diminishes Ang II-induced necroptosis in HK-2 cells and the AT2 agonist CGP42112A increases the percentage of necroptotic HK-2 cells. In addition, the current study also demonstrates that Losartan and PD123319 effectively mitigated the Ang II-induced increases in Fas and FasL signaling molecule expression. Importantly, disruption of FasL significantly suppressed Ang II-induced increases in necroptotic HK-2 cell percentages, and necroptosis-related proteins. These results suggest that Fas and FasL, as subsequent signaling molecules of AT1R and AT2R, might involve in Ang II-induced necroptosis. Taken together, our results suggest that Ang II-induced necroptosis of renal tubular cell might be involved both AT1R and AT2R and the subsequent expression of Fas, FasL signaling. Thus, AT1R and AT2R might function as critical mediators.


2016 ◽  
Vol 31 (suppl_1) ◽  
pp. i65-i65
Author(s):  
Gyu-Tae Shin ◽  
Hwa-Jung Lee ◽  
Heungsoo Kim

1997 ◽  
Vol 30 (1) ◽  
pp. 134-139 ◽  
Author(s):  
Peter D. Yorgin ◽  
Andreas A. Theodorou ◽  
Amira Al-Uzri ◽  
Karen Davenport ◽  
Leslie V. Boyer-Hassen ◽  
...  

2015 ◽  
Vol 99 (11) ◽  
pp. 2311-2316 ◽  
Author(s):  
Swati Jain ◽  
Daniel Keys ◽  
Danica Ljubanovic ◽  
Charles L. Edelstein ◽  
Alkesh Jani

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