Comparison of Pioglitazone and Metformin Efficacy against Glucocorticoid Induced Atherosclerosis and Hepatic Steatosis in Insulin Resistant Rats

Introduction: Insulin Resistance is a major cause of Atherosclerosis (AS) and Non Alcoholic Fatty Liver Disease (NAFLD). These lipid alterations in blood vessels and liver may progress to cardiovascular abnormalities and cirrhosis respectively. Drugs like pioglitazone (PIO) and metformin (MET)...

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Main Authors: I M Nagendra Nayak, Koyagura Narendar, Patil Ashok M, M G Jamadar, V Hemanth Kumar
Format: Article
Language:English
Published: JCDR Research and Publications Private Limited 2017-07-01
Series:Journal of Clinical and Diagnostic Research
Subjects:
Online Access:https://jcdr.net/articles/PDF/10193/28418_CE[Ra]_F(Sh)_PF1(RB_SS)_PFA(RB_SS).pdf
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author I M Nagendra Nayak
Koyagura Narendar
Patil Ashok M
M G Jamadar
V Hemanth Kumar
author_facet I M Nagendra Nayak
Koyagura Narendar
Patil Ashok M
M G Jamadar
V Hemanth Kumar
author_sort I M Nagendra Nayak
collection DOAJ
description Introduction: Insulin Resistance is a major cause of Atherosclerosis (AS) and Non Alcoholic Fatty Liver Disease (NAFLD). These lipid alterations in blood vessels and liver may progress to cardiovascular abnormalities and cirrhosis respectively. Drugs like pioglitazone (PIO) and metformin (MET) are effective insulin sensitizers used in T2DM. But their efficacy and tolerability needs to be compared in IR associated abnormalities. Aim: To compare the efficacy of PIO and MET in glucocorticoid induced AS, Hepatic Steatosis (HS) and IR in albino rats. Materials and Methods: Male Wistar albino rats were randomized into four groups (n=6). Group 1 (Normal control) rats consumed 2% gum acacia orally for 12 days. Group 2 {dexamethasone (DEX) control} rats were administered 2% gum acacia orally for 12 days and DEX (8 mg/kg) intraperitoneally (i.p.) from 7th to 12th day during the study period. Group 3 and 4 (PIO and MET control) rats received oral administration of PIO (45 mg/kg) and MET (1000 mg/kg) for 12 days respectively. Both groups were treated with DEX (8 mg/kg/i.p.) from 7th to 12th day during the study period. On last day, fasting blood was collected and rats were sacrificed by cervical dislocation; aorta and liver tissues were isolated for the histopathological examination. Body weight, liver weight and liver volume were measured. Blood samples were processed for biochemical parameters. The data were analysed by One-way Analysis of variance (ANOVA) followed by Scheffe’s multiple comparison post-hoc test. The statistical significance was assumed at p<0.05. Results: Our results established the possible role of DEX in the development of AS and HS. Histopathological examination of Group 2 rats treated with DEX showed a marked lipid accumulation in the aorta and liver. Administration of MET and PIO resulted in partial to complete restoration of DEX induced fatty changes in aorta and liver. Both drugs significantly (p<0.05) prevented the elevation of insulin, lipid, glucose levels, liver weight and liver volume in DEX treated rats. They had significantly (p<0.05) improved body weight and insulin sensitivity. However, PIO was highly significant (p<0.05) compared to MET in reducing DEX induced IR complications. Conclusion: These findings suggest that PIO was more effective insulin sensitizer compared to MET in reducing AS, HS and IR induced by glucocorticoids.
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spelling doaj.art-8ea264f076124b6c88c2ebf3ebf729192022-12-22T02:58:35ZengJCDR Research and Publications Private LimitedJournal of Clinical and Diagnostic Research2249-782X0973-709X2017-07-01117FC06FC1010.7860/JCDR/2017/28418.10193Comparison of Pioglitazone and Metformin Efficacy against Glucocorticoid Induced Atherosclerosis and Hepatic Steatosis in Insulin Resistant RatsI M Nagendra Nayak0Koyagura Narendar1Patil Ashok M2M G Jamadar3V Hemanth Kumar4Professor and Head, Department of Pharmacology, Mount Zion Medical College, Adoor, Kerala, India.Lecturer, Department of Pharmacology, Al-Ameen Medical College, Vijayapura, Karnataka, India.Professor and Head, Department of Pathology, Al-Ameen Medical College, Vijayapura, Karnataka, India.Professor and Head, Department of Pharmacology, Al-Ameen Medical College, Vijayapura, Karnataka, India.Lecturer, Department of Pharmacology, Al-Ameen Medical College, Vijayapura, Karnataka, India.Introduction: Insulin Resistance is a major cause of Atherosclerosis (AS) and Non Alcoholic Fatty Liver Disease (NAFLD). These lipid alterations in blood vessels and liver may progress to cardiovascular abnormalities and cirrhosis respectively. Drugs like pioglitazone (PIO) and metformin (MET) are effective insulin sensitizers used in T2DM. But their efficacy and tolerability needs to be compared in IR associated abnormalities. Aim: To compare the efficacy of PIO and MET in glucocorticoid induced AS, Hepatic Steatosis (HS) and IR in albino rats. Materials and Methods: Male Wistar albino rats were randomized into four groups (n=6). Group 1 (Normal control) rats consumed 2% gum acacia orally for 12 days. Group 2 {dexamethasone (DEX) control} rats were administered 2% gum acacia orally for 12 days and DEX (8 mg/kg) intraperitoneally (i.p.) from 7th to 12th day during the study period. Group 3 and 4 (PIO and MET control) rats received oral administration of PIO (45 mg/kg) and MET (1000 mg/kg) for 12 days respectively. Both groups were treated with DEX (8 mg/kg/i.p.) from 7th to 12th day during the study period. On last day, fasting blood was collected and rats were sacrificed by cervical dislocation; aorta and liver tissues were isolated for the histopathological examination. Body weight, liver weight and liver volume were measured. Blood samples were processed for biochemical parameters. The data were analysed by One-way Analysis of variance (ANOVA) followed by Scheffe’s multiple comparison post-hoc test. The statistical significance was assumed at p<0.05. Results: Our results established the possible role of DEX in the development of AS and HS. Histopathological examination of Group 2 rats treated with DEX showed a marked lipid accumulation in the aorta and liver. Administration of MET and PIO resulted in partial to complete restoration of DEX induced fatty changes in aorta and liver. Both drugs significantly (p<0.05) prevented the elevation of insulin, lipid, glucose levels, liver weight and liver volume in DEX treated rats. They had significantly (p<0.05) improved body weight and insulin sensitivity. However, PIO was highly significant (p<0.05) compared to MET in reducing DEX induced IR complications. Conclusion: These findings suggest that PIO was more effective insulin sensitizer compared to MET in reducing AS, HS and IR induced by glucocorticoids.https://jcdr.net/articles/PDF/10193/28418_CE[Ra]_F(Sh)_PF1(RB_SS)_PFA(RB_SS).pdfdexamethasonedyslipidemiafatty changesinsulin sensitizers
spellingShingle I M Nagendra Nayak
Koyagura Narendar
Patil Ashok M
M G Jamadar
V Hemanth Kumar
Comparison of Pioglitazone and Metformin Efficacy against Glucocorticoid Induced Atherosclerosis and Hepatic Steatosis in Insulin Resistant Rats
Journal of Clinical and Diagnostic Research
dexamethasone
dyslipidemia
fatty changes
insulin sensitizers
title Comparison of Pioglitazone and Metformin Efficacy against Glucocorticoid Induced Atherosclerosis and Hepatic Steatosis in Insulin Resistant Rats
title_full Comparison of Pioglitazone and Metformin Efficacy against Glucocorticoid Induced Atherosclerosis and Hepatic Steatosis in Insulin Resistant Rats
title_fullStr Comparison of Pioglitazone and Metformin Efficacy against Glucocorticoid Induced Atherosclerosis and Hepatic Steatosis in Insulin Resistant Rats
title_full_unstemmed Comparison of Pioglitazone and Metformin Efficacy against Glucocorticoid Induced Atherosclerosis and Hepatic Steatosis in Insulin Resistant Rats
title_short Comparison of Pioglitazone and Metformin Efficacy against Glucocorticoid Induced Atherosclerosis and Hepatic Steatosis in Insulin Resistant Rats
title_sort comparison of pioglitazone and metformin efficacy against glucocorticoid induced atherosclerosis and hepatic steatosis in insulin resistant rats
topic dexamethasone
dyslipidemia
fatty changes
insulin sensitizers
url https://jcdr.net/articles/PDF/10193/28418_CE[Ra]_F(Sh)_PF1(RB_SS)_PFA(RB_SS).pdf
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