Evaluation of the potential benefits of L-ergothioneine on selected complications associated with type-2 diabetes in a rat model.
Loading...
Date
2021
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Several pathogenic factors promote type-2 diabetic complications in patients, including cardiomyopathy,
nephropathy, and non-alcoholic fatty liver disease (NAFLD). Specific nutraceuticals from food may act as
a medicinal adjuvant in managing diabetic complications. L-ergothioneine (L-egt), a bioactive compound
obtained from medicinal mushrooms, beans and some meat products, has been shown to reduce lipid
accumulation, provide cytoprotection in tissue injury and enhances therapeutic efficacy when used as
adjuvant. This study investigated the effect of L-ergothioneine with or without metformin on pathogenic
metabolic pathways and biomarkers associated with selected diabetic complications in a type-2 diabetic rat
model.
Ninety (90) adult male Sprague-Dawley (175±20)g rats were divided into three study groups [study 1 (36),
study 2 (30) and study 3 (24)]. A 10% fructose solution was provided ad libitum to adult male Sprague-
Dawley (175±20)g rats for 14 days followed by a single intraperitoneal injection of low dose streptozotocin
(STZ 40mg/kg bwt, i.p) to induce type-2 diabetes after which the animals were randomly divided into six,
five, and four groups (n=6) in studies 1 (liver), 2 (kidney), and 3 (heart), respectively. The control groups
were administered 1ml/100g distilled water, while L-egt (35mg/kg bwt), metformin (500mg/kg bwt), and
losartan (20mg/kg bwt) were administered in the other groups. At the end of each study, animals were
euthanized via decapitation, blood samples were collected, while the heart, kidney, and liver tissue were
excised and used for biochemical, RT-qPCR, ELISA, western blotting, and histopathological analysis. An
in-silico study was done to evaluate the molecular antioxidant mechanism of L-egt.
Administration of L-egt, with or without metformin, to diabetic animals positively altered selected
biomarkers of hepatic, renal, and cardiac dysfunction and prevented structural damage in these tissues. This
treatment regimen mitigated oxidative stress, inflammation, and fibrosis by downregulating (p<0.05)
SREBP1c, FAS, NF-kB, fibronectin, TGFβ1, and Keap1 expression and upregulating (p<0.05) Nrf2, Sirt1,
NQO1, and HO1 expression compared with the diabetic control animals. Interestingly, co-administration
of L-egt and metformin improved glucose homeostasis and reduced HOMA-IR. The in-silico study showed
that L-egt binds to the active site of Nrf2 and may serve as a ligand to activate this potent antioxidant
molecule.
The overall result from this study showed the potential benefits of L-ergothioneine in the management of
selected complications associated with type-2 diabetes. This bioactive compound may be an effective
adjuvant to attenuate hypertriglyceridemia, oxidative stress, and inflammation, thereby protecting vital
organs associated with diabetic complications against injury and improving glycemic control when coadministered
with metformin to delay the onset of diabetic complications.
Description
Doctoral Degree. University of KwaZulu-Natal, Durban.