Inhibition of Diabetes Mellitus-Induced Knee Joint Injury in Rats by a Combination of Metformin and Captopril

SUMMARY: Osteoarthritis (OA) is an inflammatory disease that damages the joints and affects millions of people worldwide. The potential inhibitory effects of the antidiabetic drug metformin combined with captopril, the angiotensin-converting enzyme inhibitor, on diabetes-induced damage to the knee j...

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Autores principales: El-Bidawy,Mahmoud H, Al-Ani,Bahjat, Hussain,Abo Bakr Omar, Al-Ghamdi,Sameer, Aldossari,Khaled K, Haidara,Mohamed A
Lenguaje:English
Publicado: Sociedad Chilena de Anatomía 2021
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Acceso en línea:http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-95022021000300747
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spelling oai:scielo:S0717-950220210003007472021-07-25Inhibition of Diabetes Mellitus-Induced Knee Joint Injury in Rats by a Combination of Metformin and CaptoprilEl-Bidawy,Mahmoud HAl-Ani,BahjatHussain,Abo Bakr OmarAl-Ghamdi,SameerAldossari,Khaled KHaidara,Mohamed A Osteoarthritis Diabetes Knee joint Metformin Captopril Rat model SUMMARY: Osteoarthritis (OA) is an inflammatory disease that damages the joints and affects millions of people worldwide. The potential inhibitory effects of the antidiabetic drug metformin combined with captopril, the angiotensin-converting enzyme inhibitor, on diabetes-induced damage to the knee joint articular cartilage associated with the inhibition of glycemia, dyslipidemia, and inflammation has not been investigated before. Therefore, we induced diabetes in rats using high carbohydrate and fat diets and a single injection of streptozotocin (50 mg/kg). The protective group of rats was pre-treated with combined daily doses of metformin (Met; 200 mg/kg body weight) and captopril (Cap; 150 mg/kg body weight) for 14 days before diabetic induction and continued on metformin and resveratrol until the end of the experiment at week 12. Harvested tissues obtained from knee joints were prepared for basic histology staining with haematoxylin and eosin (H&E) and examined under light microscopy. Representative H&E images showed that OA was developed in the diabetic rats as demonstrated by a profound damage to the knee joints such as irregular eroded and a sharp decrease in the thickness of the articular cartilage surface and abnormal remodeling of the subchondral bone that were substantially ameliorated by Met+Cap. Met+Cap also significantly (p< 0.05) reduced blood levels of glucose, glycated hemoglobin (HbA1c), dyslipidemia, and the inflammatory biomarkers, high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-&#945;) induced by diabetes. In addition, a significant (p&#8804; 0.0014) correlation between the articular cartilage thickness and the blood levels of glucose, HbA1c, triglyceride (TG), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein- cholesterol (HDL-C), and hs-CRP were observed. Thus, we demonstrate that Met+Cap effectively protect the knee joint against injuries induced secondary to diabetes in rats, possibly due to the inhibition of glycemia, dyslipidemia, and biomarkers of inflammation.info:eu-repo/semantics/openAccessSociedad Chilena de AnatomíaInternational Journal of Morphology v.39 n.3 20212021-06-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-95022021000300747en10.4067/S0717-95022021000300747
institution Scielo Chile
collection Scielo Chile
language English
topic Osteoarthritis
Diabetes
Knee joint
Metformin
Captopril
Rat model
spellingShingle Osteoarthritis
Diabetes
Knee joint
Metformin
Captopril
Rat model
El-Bidawy,Mahmoud H
Al-Ani,Bahjat
Hussain,Abo Bakr Omar
Al-Ghamdi,Sameer
Aldossari,Khaled K
Haidara,Mohamed A
Inhibition of Diabetes Mellitus-Induced Knee Joint Injury in Rats by a Combination of Metformin and Captopril
description SUMMARY: Osteoarthritis (OA) is an inflammatory disease that damages the joints and affects millions of people worldwide. The potential inhibitory effects of the antidiabetic drug metformin combined with captopril, the angiotensin-converting enzyme inhibitor, on diabetes-induced damage to the knee joint articular cartilage associated with the inhibition of glycemia, dyslipidemia, and inflammation has not been investigated before. Therefore, we induced diabetes in rats using high carbohydrate and fat diets and a single injection of streptozotocin (50 mg/kg). The protective group of rats was pre-treated with combined daily doses of metformin (Met; 200 mg/kg body weight) and captopril (Cap; 150 mg/kg body weight) for 14 days before diabetic induction and continued on metformin and resveratrol until the end of the experiment at week 12. Harvested tissues obtained from knee joints were prepared for basic histology staining with haematoxylin and eosin (H&E) and examined under light microscopy. Representative H&E images showed that OA was developed in the diabetic rats as demonstrated by a profound damage to the knee joints such as irregular eroded and a sharp decrease in the thickness of the articular cartilage surface and abnormal remodeling of the subchondral bone that were substantially ameliorated by Met+Cap. Met+Cap also significantly (p< 0.05) reduced blood levels of glucose, glycated hemoglobin (HbA1c), dyslipidemia, and the inflammatory biomarkers, high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-&#945;) induced by diabetes. In addition, a significant (p&#8804; 0.0014) correlation between the articular cartilage thickness and the blood levels of glucose, HbA1c, triglyceride (TG), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein- cholesterol (HDL-C), and hs-CRP were observed. Thus, we demonstrate that Met+Cap effectively protect the knee joint against injuries induced secondary to diabetes in rats, possibly due to the inhibition of glycemia, dyslipidemia, and biomarkers of inflammation.
author El-Bidawy,Mahmoud H
Al-Ani,Bahjat
Hussain,Abo Bakr Omar
Al-Ghamdi,Sameer
Aldossari,Khaled K
Haidara,Mohamed A
author_facet El-Bidawy,Mahmoud H
Al-Ani,Bahjat
Hussain,Abo Bakr Omar
Al-Ghamdi,Sameer
Aldossari,Khaled K
Haidara,Mohamed A
author_sort El-Bidawy,Mahmoud H
title Inhibition of Diabetes Mellitus-Induced Knee Joint Injury in Rats by a Combination of Metformin and Captopril
title_short Inhibition of Diabetes Mellitus-Induced Knee Joint Injury in Rats by a Combination of Metformin and Captopril
title_full Inhibition of Diabetes Mellitus-Induced Knee Joint Injury in Rats by a Combination of Metformin and Captopril
title_fullStr Inhibition of Diabetes Mellitus-Induced Knee Joint Injury in Rats by a Combination of Metformin and Captopril
title_full_unstemmed Inhibition of Diabetes Mellitus-Induced Knee Joint Injury in Rats by a Combination of Metformin and Captopril
title_sort inhibition of diabetes mellitus-induced knee joint injury in rats by a combination of metformin and captopril
publisher Sociedad Chilena de Anatomía
publishDate 2021
url http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-95022021000300747
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