Caffeic acid phenethyl ester (CAPE) protects brain against oxidative stress and inflammation induced by diabetes in rats.
Diabetic patients reveal significant disorders, such as nephropathy, cardiomyopathy, and neuropathy. As oxidative stress and inflammation seem to be implicated in the pathogenesis of diabetic brain, we aimed to investigate the effects of caffeic acid phenethyl ester (CAPE) on oxidative stress and inflammation in diabetic rat brain. Diabetes was induced by a single dose of streptozotocin (45 mg kg(-1), i.p.) injection into rats. Two days after streptozotocin treatment 10 microM kg(-1) day(-1) CAPE was administrated and continued for 60 days. Here, we demonstrate that CAPE significantly decreased the levels of nitric oxide and malondialdehyde induced by diabetes, and the activities of catalase, glutathione peroxidase, and xanthine oxidase in the brain. However, glutathione levels were increased by CAPE. The mRNA expressions of tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma, and inducible nitric oxide synthase (iNOS) were remarkably enhanced in brain by diabetes. CAPE treatments significantly suppressed these inflammatory cytokines (about 70% for TNF-alpha, 26% for IFN-gamma) and NOS (completely). Anti-inflammatory cytokine IL-10 mRNA expression was not affected by either diabetes or CAPE treatments. In conclusion, diabetes induces oxidative stress and inflammation in the brain, and these may be contributory mechanisms involved in this disorder. CAPE treatment may reverse the diabetic-induced oxidative stress in rat brains. Moreover, CAPE reduces the mRNA expressions of TNF-alpha and IFN-gamma in diabetic brain; suggesting CAPE suppresses inflammation as well as oxidative stress occurred in the brain of diabetic patients.
Celik
Sefa
S
Department of Biochemistry, Faculty of Veterinary Medicine, Mustafa Kemal University, Tayfur Sokmen Kampusu 31034, Antakya, Hatay, Turkey. sefacelik@aku.edu.tr
Erdogan
Suat
S
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002109:Caffeic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000235:genetics; D019610:Cytoprotection / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004353:Drug Evaluation, Preclinical; D004660:Encephalitis / Q000209:etiology / Q000517:prevention & control*; D005786:Gene Expression Regulation / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D002109:Caffeic Acids; D016207:Cytokines; D018696:Neuroprotective Agents; D009569:Nitric Oxide; D013311:Streptozocin; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol