α-Lipoic Acid Increases Collagen Synthesis and Deposition in Nondiabetic and Diabetic Rat Kidneys
2021
Authors:
Grdović, NevenaRajić, Jovana
Arambašić Jovanović, Jelena
Dinić, Svetlana
Tolić, Anja
Đorđević, Miloš
Đorđević, Marija
Trifunović, Svetlana
Vidaković, Melita
Uskoković, Aleksandra
Mihailović, Mirjana
Document Type:
Article (Published version)
Metadata
Show full item recordAbstract:
α-Lipoic acid (ALA) is widely used as a nutritional supplement and therapeutic agent in diabetes management. Well-established antioxidant and hypoglycemic effects of ALA were considered to be particularly important in combating diabetic complications including renal injury. The present study evaluated the potential of ALA to affect profibrotic events in kidney that could alter its structure and functioning. ALA was administered intraperitoneally (10 mg/kg) to nondiabetic and streptozotocin-induced diabetic male Wistar rats for 4 and 8 weeks. The effects of ALA were assessed starting from structural/morphological alterations through changes that characterize profibrotic processes, to regulation of collagen gene expression in kidney. Here, we demonstrated that ALA improved systemic glucose and urea level, reduced formation of renal advanced glycation end products (AGEs), and maintained renal structural integrity in diabetic rats. However, profibrotic events provoked in diabetes were not alleviated by ALA since collagen synthesis/deposition and expression of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) remained elevated in ALA-treated diabetic rats, especially after 8 weeks of diabetes onset. Moreover, 8 weeks treatment of nondiabetic rats with ALA led to the development of profibrotic features reflected in increased collagen synthesis/deposition. Besides the TGF-β1 downstream signaling, the additional mechanism underlying the upregulation of collagen IV in nondiabetic rats treated with ALA involves decreased DNA methylation of its promoter that could arise from increased Tet1 expression. These findings emphasize the therapeutic caution in the use of ALA, especially in patients with renal diabetic complication.
Source:
Oxidative Medicine and Cellular Longevity, 2021, 2021, 6669352-Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
DOI: 10.1155/2021/6669352
ISSN: 1942-0900
PubMed: 33777319