Thiazolidinediones: a new class of drugs for the therapy of ischemia-reperfusion injury.
Synthetic peroxisome proliferator-activated receptor gamma (PPAR-gamma) ligands shown to induce adipocyte differentiation and increase insulin sensitivity, thiazolidinediones have recently been implicated as regulators of cellular inflammatory and ischemic responses. Thiazolidinediones inhibit the activity of a number of transcriptional factors, including nuclear factor-gammaB, activating protein 1, signal transducers and activated T cells, and early response gene 1 by either PPAR-gamma-dependent or -independent mechanisms. Recent experimental studies demonstrated a dramatic protection by thiazolidinediones against cardiac, gastrointestinal and lung injury after ischemia-reperfusion, in addition to a significant reduction in infiltrating neutrophils. These reports have hypothesized that the inhibition of neutrophil-mediated inflammation by thiazolidinediones is involved in the reduction of ischemia-reperfusion-induced tissue injury. Altogether, recent findings suggest that thiazolidinediones could represent a novel therapeutic approach to reducing or preventing reperfusion injury.
Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan. ynaito@koto.kpu-m.ac.jp
Yuji
Y
Naito
Toshikazu
T
Yoshikawa
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002839:Chromans / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008024:Ligands; D000077205:Pioglitazone; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use; D014157:Transcription Factors / Q000378:metabolism; D000077288:Troglitazone
D000893:Anti-Inflammatory Agents; D002839:Chromans; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone; D000077288:Troglitazone; D000077205:Pioglitazone