Definitions

high liver

Troglitazone

Troglitazone (Rezulin, Resulin or Romozin) is an anti-diabetic and antiinflammatory drug, and a member of the drug class of the thiazolidinediones. It was introduced and manufactured by Parke-Davis in the late 1990s but turned out to be associated with an idiosyncratic reaction leading to drug-induced hepatitis. Evaluating FDA medical officer Dr. John Gueriguian had disapproved it due to high liver toxicity. But the FDA stripped Gueriguian of his post and discarded his report under successful corporate pressure to approve the drug. It was withdrawn from the USA market on 21 March 2000, and from other markets soon afterwards.

Mode of action

Troglitazone, like the other thiazolidinediones (pioglitazone and rosiglitazone), works by activating PPARs (peroxisome proliferator-activated receptors). Troglitazone is a ligand to both PPARα and - more strongly - PPARγ. Troglitazone also contains an α-tocopheroyl moiety, potentially giving it vitamin E-like activity in addition to its PPAR activation. It has been shown (Aljada et al) to reduce inflammation: troglitazone use was associated with a decrease of nuclear factor kappa-B (NFκB) and a concomitant increase in its inhibitor (IκB). NFκB is an important cellular transcription regulator for the immune response.

References

  • Aljada A, Garg R, Ghanim H, et al (2001). "Nuclear factor-kappaB suppressive and inhibitor-kappaB stimulatory effects of troglitazone in obese patients with type 2 diabetes: evidence of an antiinflammatory action?". J. Clin. Endocrinol. Metab. 86 (7): 3250–6.

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