Evaluation of Acute Toxicity of Pioglitazone in Mice
Keywords:Acute toxicity, diabetes mellitus, pioglitazone, ventricular hypertrophy
AbstractObjectives: 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 The earlier drug of this group troglitazone has been withdrawn due to its liver toxicity.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 LD50 and ½ LD50 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 LD50) 500 mg/kg pioglitazone as single dose and group III (½ LD50) 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 LD50), 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 LD50), 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.
How to Cite
Mizrachi E, Bernel-Mizrachi C. Diabetes mellitus and related disorders. In: Cooper DH, Krainik AJ, Lubner SJ, Reno HEL, editors. Washington manual of medical therapeutics. 32nd ed.Wolters Kluwer/Lippincott Williums and Wilkins2007; Philadelphia, PA; p. 600-23.
Fauci AS, Braunwald E, Casper DL, Hauser SL, Lango DL, Jameson JL, et al., editors. Harrison's Principles of Internal Medicine. 17th ed. The McGraw Hill Companies; 2008.New York, NY: p. 2275-304.
American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2010;33:S62-9.
Martha S. Nolte. Pancreatic hormones and Antidiabetic drugs.In: Katzung BG, Masters SB, Trevor AJ, editors. Basic and clinical pharmacology. 11th ed. New Delhi: Tata McGraw Hill Education Private Limited; 2009. p. 727-51.
Brunton LL, Lazo JS, Parker KL, editors. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11th ed. McGraw Medical Publishing Division United States of America; 2006.
Watkins PB, Whitcomb RW. Hepatic dysfunction associated with troglitazone. N Engl J Med 1998;338:916-7.
Ghosh MN. Fundamentals of Experimental Pharmacology. 3rd ed.Kolkata: Hilton and Company; 2005. p. 190-7.
Kahn CR, Weir GC, King GL, Jacobson AM, Moses AC, Smith RJ, editors. Joslin's Diabetes mellitus. 14th ed. Lippincott Williams and Wilkins a Walters Kluwer Company; Boston, MA: 2006.
PDR Staff and Physicians. Physician's Desk Reference. 63rd ed.Thomson PDR; Montvale, NJ 2009. p. 3073