PMID- 35286963
OWN - NLM
STAT- MEDLINE
DCOM- 20220427
LR  - 20220427
IS  - 1950-6007 (Electronic)
IS  - 0753-3322 (Linking)
VI  - 149
DP  - 2022 May
TI  - Supplementation of conventional anti-diabetic therapy with alpha-lipoic acid 
      prevents early development and progression of diabetic nephropathy.
PG  - 112818
LID - S0753-3322(22)00206-2 [pii]
LID - 10.1016/j.biopha.2022.112818 [doi]
AB  - BACKGROUND: Diabetic nephropathy (DN) is the leading cause of end-stage renal 
      disease. Current pharmacological interventions only retard DN progression. 
      Alpha-lipoic acid (ALA) is a potent antioxidant with beneficial effect in other 
      diabetic complications. This study investigates whether ALA supplementation 
      prevents early development and progression of DN. METHOD: Fifty-eight male 
      Sprague-Dawley rats were randomly assigned to healthy control and diabetic groups 
      and subjected to overnight fasting. Type 2 diabetes mellitus (T2DM) was induced 
      in diabetic group by intraperitoneal administration of nicotinamide (110 mg/kg) 
      and streptozotocin (55 mg/kg). On day 3 after T2DM induction, diabetic rats 
      received oral daily administration of ALA (60 mg/kg), gliclazide (15 mg/kg), 
      ramipril (10 mg/kg) or drug combinations for 6 weeks. Untreated diabetic rats 
      served as diabetic control. Blood, kidneys and pancreas were harvested for 
      biochemical and histological analyses. RESULT: Induction of T2DM resulted in 
      hypoinsulinemia, hyperglycemia and renal pathology. ALA supplementation 
      maintained beta-cell function, normoinsulinemia and normoglycemia in diabetic rats, 
      and prevented renal pathology (PAS, KIM-1, plasma creatinine, total protein, 
      blood urea nitrogen, uric acid and urine albumin/creatinine ratio) and 
      triglycerides level compared to diabetic control (p < 0.001). Additionally, ALA 
      supplementation significantly prevented elevated serum and tissue 
      malondialdehyde, collagen deposition, alpha-SMA expression, apoptosis and serum IL-1beta 
      and IL-6 levels while it markedly increased renal glutathione content and plasma 
      HDL-C compared to diabetic control group (p < 0.001). CONCLUSION: ALA 
      supplementation prevents early development and progression of DN by exerting 
      anti-hyperglycemic, antioxidant, anti-inflammatory, anti-fibrotic and 
      anti-apoptotic effects. Our findings provide additional option for clinical 
      treatment of DN in T2DM patients.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier Masson SAS.. All rights 
      reserved.
FAU - Dugbartey, George J
AU  - Dugbartey GJ
AD  - Department of Pharmacology and Toxicology, School of Pharmacy, College of Health 
      Sciences, University of Ghana, Legon, Accra, Ghana. Electronic address: 
      gjdugbartey@ug.edu.gh.
FAU - Alornyo, Karl K
AU  - Alornyo KK
AD  - Department of Pharmacology and Toxicology, School of Pharmacy, College of Health 
      Sciences, University of Ghana, Legon, Accra, Ghana.
FAU - N'guessan, Benoit B
AU  - N'guessan BB
AD  - Department of Pharmacology and Toxicology, School of Pharmacy, College of Health 
      Sciences, University of Ghana, Legon, Accra, Ghana.
FAU - Atule, Stephen
AU  - Atule S
AD  - Department of Pharmacology and Toxicology, School of Pharmacy, College of Health 
      Sciences, University of Ghana, Legon, Accra, Ghana.
FAU - Mensah, Samuel D
AU  - Mensah SD
AD  - Department of Pathology, University of Ghana Dental School, College of Health 
      Sciences, University of Ghana, Legon, Accra, Ghana.
FAU - Adjei, Samuel
AU  - Adjei S
AD  - Department of Animal Experimentation, Noguchi Memorial Institute for Medical 
      Research, College of Health Sciences, University of Ghana, Legon, Accra, Ghana.
LA  - eng
PT  - Journal Article
DEP - 20220311
PL  - France
TA  - Biomed Pharmacother
JT  - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
JID - 8213295
RN  - 0 (Antioxidants)
RN  - 73Y7P0K73Y (Thioctic Acid)
RN  - AYI8EX34EU (Creatinine)
SB  - IM
MH  - Animals
MH  - Antioxidants/metabolism
MH  - Creatinine
MH  - *Diabetes Mellitus, Experimental/complications/drug therapy/metabolism
MH  - *Diabetes Mellitus, Type 2/complications/drug therapy/metabolism
MH  - *Diabetic Nephropathies/drug therapy/metabolism/prevention & control
MH  - Dietary Supplements
MH  - Female
MH  - Humans
MH  - Kidney
MH  - Male
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - *Thioctic Acid/pharmacology/therapeutic use
OTO - NOTNLM
OT  - Alpha-lipoic acid (ALA)
OT  - Conventional anti-diabetic therapy
OT  - Diabetic nephropathy (DN)
OT  - Triple combination therapy
OT  - Type 2 diabetes mellitus (T2DM)
EDAT- 2022/03/15 06:00
MHDA- 2022/04/28 06:00
CRDT- 2022/03/14 20:11
PHST- 2022/01/08 00:00 [received]
PHST- 2022/03/07 00:00 [revised]
PHST- 2022/03/09 00:00 [accepted]
PHST- 2022/03/15 06:00 [pubmed]
PHST- 2022/04/28 06:00 [medline]
PHST- 2022/03/14 20:11 [entrez]
AID - S0753-3322(22)00206-2 [pii]
AID - 10.1016/j.biopha.2022.112818 [doi]
PST - ppublish
SO  - Biomed Pharmacother. 2022 May;149:112818. doi: 10.1016/j.biopha.2022.112818. Epub 
      2022 Mar 11.