ABSTRACT
The present study was undertaken to evaluate the effect of kaempferol in isoprenaline (ISP)-induced myocardial injury in rats. ISP was administered subcutaneously for two subsequent days to induce myocardial injury. Assessment of myocardial injury was done by estimation of hemodynamic functions, myocardial infarcted area, cardiac injury markers, lipid profile, oxidative stress, pro-inflammatory cytokines and histopathology of heart and liver. Rats pretreated with kaempferol showed reduction in the myocardial infarcted area and heart rate. However, no improvement was observed in change in body weight, mean arterial, systolic and diastolic blood pressure. Kaempferol showed significant decrease in serum LDH, CK-MB, troponin-I and lipid profile. However, highest dose of kaempferol did not reduce the serum triglyceride level. Further, antioxidant enzymes, SOD and catalase, were also higher. However, reduced glutathione, serum SGOT and creatinine did not show any improvement. Kaempferol showed reduction in MDA level. Kaempferol at highest dose showed reduction in pro-MMP-2 expression and MMP-9 level. mRNA expression level of TNF-α was not different in kaempferol-pretreated myocardial injured rats with ISP-alone group. Pretreatment with kaempferol at highest dose showed mild mononuclear infiltration and degenerative changes in heart tissue section of myocardial injured rats. Rats pretreated with kaempferol at higher concentration showed normal cordlike arrangement of hepatocytes with moderate swelling of hepatocytes (vacuolar degeneration) around the central vein. Study suggests that kaempferol attenuated lipid profile, infarcted area and oxidative stress in ISP-induced myocardial injury in rats.
Subject(s)
Antioxidants/pharmacology , Kaempferols/pharmacology , Myocardial Infarction/prevention & control , Myocytes, Cardiac/drug effects , Animals , Antioxidants/toxicity , Biomarkers/blood , Cytoprotection , Disease Models, Animal , Dose-Response Relationship, Drug , Enzyme Precursors/genetics , Enzyme Precursors/metabolism , Gelatinases/genetics , Gelatinases/metabolism , Heart Rate/drug effects , Hepatocytes/drug effects , Hepatocytes/metabolism , Hepatocytes/pathology , Isoproterenol , Kaempferols/toxicity , Lipid Peroxidation/drug effects , Lipids/blood , Liver/drug effects , Liver/metabolism , Liver/pathology , Male , Matrix Metalloproteinase 9/metabolism , Myocardial Infarction/chemically induced , Myocardial Infarction/metabolism , Myocardial Infarction/pathology , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Oxidative Stress/drug effects , Rats, WistarABSTRACT
BACKGROUND: Administration of recombinant erythropoietin (rEPO) is often associated with systemic and pulmonary arterial hypertension in animals and human. The present study was conducted to determine whether one-week rEPO-treatment can produce any effect on pulmonary vasomotor function. METHODS: Male Wistar rats were injected with rEPO (400IU/kg sc) or saline every other day for one week. Tension, biochemical and Real-Time PCR experiments were conducted on left and right branches of pulmonary artery and main pulmonary artery isolated from the rats. RESULTS: ACh-induced relaxation was significantly (p<0.05) reduced in rEPO-treated rats in comparison to control animals. Relaxation to the NO donor SNP was not different between the groups. EDHF-induced relaxation was remarkably higher in rEPO-treated group in comparison to control. Phenylephrine-induced contraction was significantly (p <0.05) reduced in rings from rEPO-treated rats at the second and third lowest concentrations of phenylephrine and its potency was not significantly reduced. No significant difference was observed in CaCl2-induced contraction between the groups. Nitric oxide production was significantly reduced in rEPO-treated rats in comparison to control animals. Real-time PCR studies demonstrated a significant decrease (p<0.05) of eNOS transcript. However, peNOS activity was not altered with rEPO treatment. CONCLUSION: The present study suggests that EPO-treatment for one week attenuates ACh-stimulated NO production. It does not affect the vasodilatory action of SNP. It showed up-regulation of EDHF and decreased potency of phenylephrine. Thus elevated EPO may diversely affect the vasomotor function of pulmonary artery. Clinically, it is important to observe the use of EPO in hypertensive condition.
