Rosiglitazone, a PPAR-gamma ligand, protects against burn-induced oxidative injury of remote organs.
Severe burn induces the activation of an inflammatory cascade that contributes to the development of subsequent immunosuppression, increased susceptibility to sepsis, as well as generation of reactive oxygen radicals and lipid peroxidation, leading to multiple organ failure. In the present study, we investigated whether rosiglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligand is protective against burn-induced remote organ injury. Under brief ether anaesthesia, shaved dorsum of the rats were exposed to 90 degrees C (burn group) or 25 degrees C (control group) water bath for 10s. Rosiglitazone (4 mg/kg) or saline was administered intraperitoneally immediately after and at the 12th hour of the burn. Rats were decapitated 24h after injury and the tissue samples from lung, liver, and kidney were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels, and creatinine, blood urea concentrations (BUN) were determined to assess liver and kidney function, respectively. Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and lactate dehydrogenase (LDH) were also assayed. Severe skin scald injury (30% of total body surface area) caused a significant decrease in GSH level, and significant increases in MDA level, MPO activity and collagen content of tissues. Similarly, serum ALT, AST and BUN levels, as well as LDH, IL-1 beta and TNF-alpha were elevated in the burn group as compared to the control group. Rosiglitazone treatment reversed all these biochemical indices. According to the findings of the present study, rosiglitazone possesses a anti-inflammatory effect that prevents burn-induced damage in remote organs and protects against organ damage.
Sener
Göksel
G
Marmara University, School of Pharmacy, Department of Pharmacology, Istanbul, Turkey. gsener@marmara.edu.tr
Sehirli
A Ozer
AO
Gedik
Nursal
N
Dülger
Gül Ayanoğlu
GA
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002056:Burns / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000378:metabolism; D007674:Kidney Diseases / Q000378:metabolism / Q000517:prevention & control; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism / Q000517:prevention & control; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014508:Urea / Q000097:blood
D007004:Hypoglycemic Agents; D053583:Interleukin-1beta; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D000077154:Rosiglitazone; D008315:Malondialdehyde; D014508:Urea; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase