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Evaluation of Acute Toxicity of Pioglitazone in Mice

OBJECTIVES: The primary objective of the study is to assess the toxic effect of pioglitazone in mice. Pioglitazone belongs to thiazolidinedione group of oral antidiabetic agents. The earlier drug of this group troglitazone has been withdrawn due to its liver toxicity. The other drug rosiglitazone wh...

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Autores principales: Chinnam, Pushpalatha, Mohsin, Mohammed, Shafee, Leena M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3532769/
https://www.ncbi.nlm.nih.gov/pubmed/23293462
http://dx.doi.org/10.4103/0971-6580.103660
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author Chinnam, Pushpalatha
Mohsin, Mohammed
Shafee, Leena M.
author_facet Chinnam, Pushpalatha
Mohsin, Mohammed
Shafee, Leena M.
author_sort Chinnam, Pushpalatha
collection PubMed
description OBJECTIVES: The primary objective of the study is to assess the toxic effect of pioglitazone in mice. Pioglitazone belongs to thiazolidinedione group of oral antidiabetic agents. The earlier drug of this group troglitazone has been withdrawn due to its liver toxicity. The other drug rosiglitazone which was used like pioglitazone as insulin sensitizing agent in type 2 diabetes has been banned due to its cardiovascular side effects, recently. So, Pioglitazone was administered in high doses ¼ LD(50) and ½ LD(50) in mice to assess the acute toxic effect which also correlate with accidental over dose. MATERIALS AND METHODS: Swiss albino mice of either sex weighing between 20 and 35 gm were selected. 18 mice were taken and divided into 3 groups of 6 each. The mice were kept for overnight fasting and on the following day group I (control) was administered 0.5 ml distilled water as single dose, group II (¼ LD(50)) 500 mg/kg pioglitazone as single dose and group III (½ LD(50)) 1000 mg/kg pioglitazone as single dose, orally. All the animals had free access to food and water after drug administration. After 24 hours, mice were sacrificed by cervical dislocation. Heart, liver and kidneys were dissected and subjected to histopathological examination. RESULTS: In group I (control), the histopathological examination of heart, liver and kidneys revealed no changes. In group II (¼ LD(50)), there was ventricular hypertrophy of heart in 4 out of 6 mice. Mild congestion of liver and kidneys was seen in 4 out of 6 and 2 out of 6 mice, respectively. In group III (½ LD(50)), 2 mice out of 6 have died within 24 hours of pioglitazone administration. The histopathological studies of remaining 4 mice have shown ventricular hypertrophy of heart and congestion of liver and kidneys. CONCLUSIONS: Acute administration of large doses of pioglitazone has shown ventricular hypertrophy with congestion of liver and kidneys in mice which can happen with accidental overdose of pioglitazone in patients. It is therefore advisable not to prescribe pioglitazone in diabetic patients having congestive heart failure as well as in patients having chronic hypertension, since chronic hypertension leads to ventricular hypertrophy which might get worsened.
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spelling pubmed-35327692013-01-04 Evaluation of Acute Toxicity of Pioglitazone in Mice Chinnam, Pushpalatha Mohsin, Mohammed Shafee, Leena M. Toxicol Int Original Article OBJECTIVES: The primary objective of the study is to assess the toxic effect of pioglitazone in mice. Pioglitazone belongs to thiazolidinedione group of oral antidiabetic agents. The earlier drug of this group troglitazone has been withdrawn due to its liver toxicity. The other drug rosiglitazone which was used like pioglitazone as insulin sensitizing agent in type 2 diabetes has been banned due to its cardiovascular side effects, recently. So, Pioglitazone was administered in high doses ¼ LD(50) and ½ LD(50) in mice to assess the acute toxic effect which also correlate with accidental over dose. MATERIALS AND METHODS: Swiss albino mice of either sex weighing between 20 and 35 gm were selected. 18 mice were taken and divided into 3 groups of 6 each. The mice were kept for overnight fasting and on the following day group I (control) was administered 0.5 ml distilled water as single dose, group II (¼ LD(50)) 500 mg/kg pioglitazone as single dose and group III (½ LD(50)) 1000 mg/kg pioglitazone as single dose, orally. All the animals had free access to food and water after drug administration. After 24 hours, mice were sacrificed by cervical dislocation. Heart, liver and kidneys were dissected and subjected to histopathological examination. RESULTS: In group I (control), the histopathological examination of heart, liver and kidneys revealed no changes. In group II (¼ LD(50)), there was ventricular hypertrophy of heart in 4 out of 6 mice. Mild congestion of liver and kidneys was seen in 4 out of 6 and 2 out of 6 mice, respectively. In group III (½ LD(50)), 2 mice out of 6 have died within 24 hours of pioglitazone administration. The histopathological studies of remaining 4 mice have shown ventricular hypertrophy of heart and congestion of liver and kidneys. CONCLUSIONS: Acute administration of large doses of pioglitazone has shown ventricular hypertrophy with congestion of liver and kidneys in mice which can happen with accidental overdose of pioglitazone in patients. It is therefore advisable not to prescribe pioglitazone in diabetic patients having congestive heart failure as well as in patients having chronic hypertension, since chronic hypertension leads to ventricular hypertrophy which might get worsened. Medknow Publications & Media Pvt Ltd 2012 /pmc/articles/PMC3532769/ /pubmed/23293462 http://dx.doi.org/10.4103/0971-6580.103660 Text en Copyright: © Toxicology International http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Chinnam, Pushpalatha
Mohsin, Mohammed
Shafee, Leena M.
Evaluation of Acute Toxicity of Pioglitazone in Mice
title Evaluation of Acute Toxicity of Pioglitazone in Mice
title_full Evaluation of Acute Toxicity of Pioglitazone in Mice
title_fullStr Evaluation of Acute Toxicity of Pioglitazone in Mice
title_full_unstemmed Evaluation of Acute Toxicity of Pioglitazone in Mice
title_short Evaluation of Acute Toxicity of Pioglitazone in Mice
title_sort evaluation of acute toxicity of pioglitazone in mice
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3532769/
https://www.ncbi.nlm.nih.gov/pubmed/23293462
http://dx.doi.org/10.4103/0971-6580.103660
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