In vitro and in vivo tenocyte-protective effectiveness of dehydroepiandrosterone against high glucose-induced oxidative stress

Abstract

Background Dehydroepiandrosterone (DHEA), an adrenal steroid, has a protective role against diabetes. This study aimed to investigate the in vitro and in vivo protective effects of DHEA against high glucose-induced oxidative stress in tenocytes and tendons. Methods Tenocytes from normal Sprague-Dawley rats were cultured in low-glucose (LG) or high-glucose (HG) medium with or without DHEA. The experimental groups were: control group (LG without DHEA), LG with DHEA, HG without DHEA, and HG with DHEA. Reactive oxygen species (ROS) production, apoptosis, and messenger RNA (mRNA) expression of NADPH oxidase (NOX) 1 and 4, and interleukin-6 (IL-6) were determined. Further, diabetic rats were divided into a control group and a DHEA-injected group (DHEA group). NOX1 and NOX4 protein expression and mRNA expression of NOX1, NOX4, IL-6, matrix metalloproteinase (MMP)-2, tissue inhibitors of matrix metalloproteinase (TIMP)-2, and type I and III collagens in the Achilles tendon were determined. Results In rat tenocytes, DHEA decreased the expression of NOX1 and IL-6, ROS accumulation, and apoptotic cells. In the diabetic rat Achilles tendon, NOX1 protein expression and mRNA expression of NOX1, IL-6, MMP-2, TIMP-2, and type III collagen were significantly lower while type I collagen expression was significantly higher in the DHEA group than in the control group. Conclusions DHEA showed antioxidant and anti-inflammatory effects both in vitro and in vivo. Moreover, DHEA improved tendon matrix synthesis and turnover, which are affected by hyperglycemic conditions. DHEA is a potential preventive drug for diabetic tendinopathy.

Antioxidant effect of nicotinamide mononucleotide in tendinopathy

“…Reports on the involvement of high cellularity in tendinopathy are limited to histopathological findings, and there are no reports showing that tenocytes in tendinopathy models are highly proliferative in vitro. Furthermore, previous studies of tendinopathy models with hyperglycemia also support the present in vitro results [ 16 , 27 ].…”

“…The rats were euthanized by inhalation of isoflurane and an overdose of sodium pentobarbital (200 mg/kg; Kyoritsu Seiyaku Corp.) administered by intraperitoneal injection 2 weeks after treatment with NMN or PBS. The sample size for the in vivo experiments was calculated based on previous studies [ 27 ], using a priori power analysis (α < 0.05, 1-β ≥ 0.8) in G*Power (v 3.1; Düsseldorf University), and the sample size required for each group in the unpaired t -test was n = 4. The number of rats to be sacrificed was reduced by performing collagenase injections into the bilateral Achilles tendons.…”

“…The sections were incubated with proteinase for 10 min and treated with 3% hydrogen peroxide (Wako Pure Chemical Corp.) to block endogenous peroxidase activity, and then incubated with anti-NOX1 or anti-NOX4 antibodies (both 1:1000; Abcam, Cambridge, UK) overnight at 4 °C. Sections were incubated with a peroxidase-labeled secondary antibody (Nichirei Bioscience, Tokyo, Japan) for 30 min at room temperature, followed by incubation with 3,3′-diaminobenzidine peroxidase substrate (Nichirei Bioscience) [ 11 , 27 ]. Sections were counterstained with hematoxylin.…”

Tamsulosin attenuates high glucose- induced injury in glomerular endothelial cells

“…High glucose is well known to be one of the most important risk factors contributing to the pathogenesis of DN by inducing the dysfunction of GECs [ 8 ]. High glucose is reported to cause oxidative stress by promoting ROS overproduction in mitochondria [ 9 , 10 ]. Additionally, excessive generations of TNF-α, IL-6, and IL-8 have been considered as a prerequisite for microvasculature endothelial dysfunction under high-glucose conditions.…”

A dancer, a groomer, a folk artist and a viola player – case reports of occupational musculoskeletal and peripheral nervous system diseases

“…Patogeneza tendinopatii cukrzycowej nie została w pełni poznana, uważa się jednak, że przyczyną mogą być m.in. wzrost nieprawidłowych produktów glikacji, wzrost aktywności reaktywnych form tlenu oraz zaburzenie angiogenezy i różnicowania włókien kolagenowych pochewek i ścięgien [7]. W badaniu przedmiotowym wyczuwalne jest zgrubienie oraz obrzęk w okolicy pochewki, a chory odczuwa ból podczas wykonywania ruchów czynnych i biernych angażujących ścięgno objęte procesem chorobowym [5].…”