Ameliorative effect of combination of fenofibrate and rosiglitazone in pressure overload-induced cardiac hypertrophy in rats.
The present study has been designed to investigate the effects of fenofibrate, a peroxisome proliferator-activated receptor (PPAR)alpha agonist, rosiglitazone, a PPARgamma agonist and the combination of both fenofibrate and rosiglitazone in partial abdominal aortic constriction (PAAC)-induced pathological cardiac hypertrophy in rats. Rats were subjected to PAAC for 4 weeks to produce pathological cardiac hypertrophy. The fenofibrate (3 mg/kg day(-1), p.o.), rosiglitazone (3 mg/kg day(-1), p.o.) and the combination of both fenofibrate (3 mg/kg day(-1), p.o.) and rosiglitazone (3 mg/kg day(-1), p.o.) were administered 3 days before PAAC and continued for 4 weeks after PAAC. The development of cardiac hypertrophy was assessed in terms of measuring ratio of left ventricular (LV) weight to body weight (LVW/BW), LV wall thickness (LVWT), LV protein content and LV collagen content. Further, the collagen accumulation in left ventricle was analyzed using picrosirius red staining. Moreover, the cross-sectional area (CSA) of cardiomyocytes was assessed using hematoxylin and eosin staining and measured using a NIH Scion image analyzer. The PAAC produced cardiac hypertrophy by increasing LVW/BW, LVWT, LV protein content, LV collagen content and mean CSA of cardiomyocytes. However, treatment with fenofibrate and rosiglitazone either alone or in combination significantly attenuated PAAC-induced increase in LVW/BW, LVWT, LV protein content, LV collagen content and mean CSA of cardiomyocytes. The combination of fenofibrate and rosiglitazone was more effective in attenuating the PAAC-induced cardiac hypertrophy than either drug alone. Thus, it may be concluded that dual activation of PPARalpha and PPARgamma may provide synergistic benefits in preventing the development of pathological cardiac hypertrophy.
Rose
Madhankumar
M
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, India.
Balakumar
Pitchai
P
Singh
Manjeet
M
D000704:Analysis of Variance; D000818:Animals; D001012:Aorta, Abdominal; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D003094:Collagen / Q000378:metabolism; D003251:Constriction, Pathologic / Q000150:complications; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D011345:Fenofibrate / Q000008:administration & dosage / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000473:pathology; D009929:Organ Size; D047493:PPAR alpha / Q000819:agonists*; D047495:PPAR gamma / Q000819:agonists*; D051381:Rats; D017208:Rats, Wistar; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology*; D016277:Ventricular Function, Left
D007004:Hypoglycemic Agents; D047493:PPAR alpha; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D003094:Collagen; D011345:Fenofibrate