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Comparison of metformin, rosiglitazone, and acetaminophen in the prevention of olanzapine toxicity in mice

Woods, Sally
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1305892985

Abstract Details

2011, MS, University of Cincinnati, Medicine: Toxicology (Environmental Health).
BACKGROUND: Olanzapine (OLZ) is an atypical antipsychotic drug that induces weight gain and diabetogenic effects in a subset of patients. Conventional anti-diabetic drugs such as Metformin (MET) and Rosiglitazone (ROSI) are often prescribed to minimize these effects. Recent evidence suggests that acetaminophen (APAP) may be an effective alternative as well. PURPOSE: 1. Directly compare APAP to MET and ROSI in its ability to prevent or reverse metabolic changes due to the administration of the atypical antipsychotic drug olanzapine (OLZ) in C57BL/6J mice consuming a high fat diet. 2. Determine if APAP cotreatment improves the efficacy of ROSI and/or MET. METHODS: Experiment I : Utilizing a prevention protocol, mice received a HF diet and tap water supplemented with OLZ [3 mg/(kg BW•d)], plus either no treatment, APAP [25 mg/(kg BW•d)], MET [200 mg/(kg BW•d)], or APAP+MET for 10 weeks. Experiment II: Utilizing a reversal protocol, mice received the same treatments as in experiment I. Mice began the reversal after 18 weeks of OLZ treatment and continued for 11 weeks. Experiment III: Utilizing a prevention protocol, mice received a HF diet and tap water supplemented with OLZ, plus either no treatment, APAP, ROSI [3 mg/(kg BW•d)], or APAP+ROSI for 14 weeks. Experiment IV: Utilizing a reversal protocol, mice received the same treatments as in experiment III. Mice began the reversal after 8 weeks of OLZ treatment and continued for 7 weeks. Body weight gain, body fat percentage, glucose tolerance, fasting blood glucose (FBG), fasting blood insulin, insulin resistance, and glycosylated hemoglobin were measured in all experiments. RESULTS: Experiment I: APAP significantly reduced FBG. MET reduced the OLZ-induced increase in body fat percentage, impaired glucose tolerance, FBG, insulin resistance, improved glucose tolerance, and glycosylated hemoglobin. Combined treatment with APAP + MET was more effective than either treatment alone in reducing rate of body weight gain, FBG, and insulin resistance. Experiment II: Neither APAP, MET, nor APAP+MET were capable of reversing any of the OLZ-induced diabetogenic effects. Experiment III: APAP, ROSI, and APAP+ROSI significantly prevented the OLZ-induced increase in body fat percentage. However, combined APAP+ROSI significantly increased insulin resistance. No effects on rate of body weight gain, glucose tolerance or glycosylated hemoglobin levels were observed. Experiment IV: APAP significantly improved glucose tolerance. ROSI significantly reversed the increase in FBG and insulin resistance associated with OLZ supplement but decreased glucose tolerance. APAP+ROSI significantly decreased FBG levels but increased glucose intolerance and insulin resistance. The reversal treatments had no effect on systemic parameters. CONCLUSION: In the mouse, MET appeared to be a better drug than APAP or ROSI in the prevention of OLZ-induced pre-diabetic changes whereas ROSI appeared to be marginally better than APAP or MET in the reversal of OLZ-induced pre-diabetic changes. While treatment with APAP+MET may improve some pre-diabetic risk factors, concerns regarding the effect of APAP on chronic levels of blood glucose may limit its clinical relevance.
Howard Shertzer, PhD (Committee Chair)
Mary Beth Genter, PhD (Committee Member)
46 p.
Toxicology
metformin; acetaminophen; rosiglitazone; olanzapine; metabolic disease; mice

Recommended Citations

Citations

  • Woods, S. (2011). Comparison of metformin, rosiglitazone, and acetaminophen in the prevention of olanzapine toxicity in mice [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1305892985

    APA Style (7th edition)

  • Woods, Sally. Comparison of metformin, rosiglitazone, and acetaminophen in the prevention of olanzapine toxicity in mice. 2011. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1305892985.

    MLA Style (8th edition)

  • Woods, Sally. "Comparison of metformin, rosiglitazone, and acetaminophen in the prevention of olanzapine toxicity in mice." Master's thesis, University of Cincinnati, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1305892985

    Chicago Manual of Style (17th edition)

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© 2011, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.