ABSTRACT
OBJECTIVE: This research was aimed to explore protective effects of allicin on rat model of myocardial infarction via JNK signaling pathway. METHODS: Rat myocardial ischemia model was established with subcutaneous injection of isoproterenol (ISO). Seventy-five rats were randomly divided into 5 groups (n = 15): sham group, ISO group, low-dose group (1.2 mg/kg/days for 7 days), medium-dose group (1.8 mg/kg/days for 7 days), and high-dose group (3.6 mg/kg/days for 7 days). Routine HE staining and Masson staining were performed to observe myocardial histopathology. The expression of oxidative stress-related indicators, heart tissue apoptosis-related proteins, and JNK and p-JNK proteins were measured for different groups. RESULTS: Compared with the sham group, the T wave value of the ISO group was significantly increased (p < 0.01). When allicin was administered, the T wave values at different time points in all groups were all decreased. Compared with the sham group, the ratio of eNOS, Bcl-2/Bax was significantly decreased, and p-eNOS, iNOS, caspase-3, caspase-9, and Cyt-c were significantly elevated in the ISO group (p < 0.05). After allicin was administered, significant changes in these proteins were observed in the medium- and high-dose groups. There was no significant change in the expression of JNK protein in the ISO group compared with the sham group; however, the expression of eNOS and p-JNK protein were significantly upregulated (p < 0.01) and the expression of p-eNOS and iNOS were significantly downregulated (p < 0.01). When allicin was administered, expression of p-JNK protein was significantly downregulated. CONCLUSION: Allicin can reduce oxidative stress damage and cardiomyocyte apoptosis in rat model of myocardial infarction and can significantly regulate JNK signaling pathway.
Subject(s)
Antioxidants/pharmacology , MAP Kinase Signaling System/drug effects , Myocardial Infarction/drug therapy , Myocardial Infarction/metabolism , Sulfinic Acids/pharmacology , Animals , Antioxidants/therapeutic use , Apoptosis/drug effects , Disease Models, Animal , Disulfides , Isoproterenol/toxicity , JNK Mitogen-Activated Protein Kinases/drug effects , JNK Mitogen-Activated Protein Kinases/metabolism , Male , Myocardial Infarction/chemically induced , Myocardium/metabolism , Myocardium/pathology , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Nitric Oxide Synthase Type II/drug effects , Nitric Oxide Synthase Type II/metabolism , Nitric Oxide Synthase Type III/drug effects , Nitric Oxide Synthase Type III/metabolism , Oxidative Stress/drug effects , Rats , Rats, Sprague-Dawley , Sulfinic Acids/therapeutic useABSTRACT
BACKGROUND The aim of this study was to explore the effect of baicalein on diabetic cardiomyopathy (DCM) rats and the mechanisms involved, and to determine the theoretical basis for clinical anti-tumor therapy. MATERIAL AND METHODS DCM rat model was induced with a single injection of streptozotocin. Then, DCM rats were treated with baicalein alone or co-treated with baicalein and PI3K/Akt inhibitor. Myocardial pathological changes were detected by HE and Masson staining. The activities of SOD, GSH-Px, and MDA in myocardial tissue were measured by biochemical tests. The levels of TNF-α, IL-1ß, and cTn-I were examined by ELISA. NADP+/NADPH ratio was measured with the NADP+/NADPH assay kit. RT-PCR was used to detect the levels of PI3K and Akt. The levels of Bax, Bcl-2, Caspase-3, GSK-3ß, PI3K, and Akt were detected by Western blot. RESULTS Baicalein could improve pathological injury. SOD and GSH-Px activity decreased while the level of MDA increased in myocardial tissue. Baicalein treatment enhanced SOD activity in a dose-dependent manner but markedly reduced MDA. Similar changes were observed in both serum inflammatory factors and the NADP+/NADPH ratio. After adding PI3K-Akt inhibitor, the levels of PI3K and Akt mRNA expression were significantly decreased, but were not significantly different from the DCM group. Levels of Bcl-2, PI3K, p-GSK-3ß/GSK-3ß, and p-Akt were decreased in the DCM group, while the levels of Bax and Caspase-3 were obviously increased. CONCLUSIONS Baicalein can protect DCM rats against damage from oxidative stress and inflammation in myocardial tissue, and PI3K/Akt signaling pathway may be involved to mediating these effects.
Subject(s)
Diabetic Cardiomyopathies/drug therapy , Flavanones/pharmacology , Animals , China , Disease Models, Animal , Flavanones/metabolism , Inflammation/drug therapy , Male , Myocardial Reperfusion Injury/metabolism , Myocardium/pathology , Oxidative Stress/drug effects , Phosphatidylinositol 3-Kinase/drug effects , Phosphatidylinositol 3-Kinase/metabolism , Protective Agents/pharmacology , Proto-Oncogene Proteins c-akt/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Rats , Rats, Sprague-Dawley , Signal Transduction/drug effectsABSTRACT
OBJECTIVE: To study the efficacy of thalidomide for treating acute leukemia (AL). METHODS: 38 cases of AL were studied. 27 of the 38 cases receiving initial treatment were randomly divided into two groups, one treated with routine chemotherapy plus thalidomide (A) and the other with routine chemotherapy alone (B). 11 of the 38 were relapsing cases and all treated with routine chemotherapy plus thalidomide (C). Marrow microvascular density (MVD) and vascular endothelial growth factor (VEGF) were examined with factor-VIII related antigen/CD(34) immunohistological stain and ELISA respectively before and after the treatment. The initial dose of thalidomide was 200 mg/d and increased to 400 - 500 mg/d by increasing 50 mg/d weekly for 4 to 6 months. RESULTS: The complete remission (CR) rate and efficacy rate were 57.1%, 53.8% and 78.6%, 76.9% in the two groups respectively with no statistical difference. The CR rate and efficacy rate in the relapsing group were 27.3%, 54.5%. The relapsing rate 6 months after the treatment was low in the thalidomide group. MVD and VEGF were significantly different before and after the treatment (P < 0.001). There was a negative correlation between the MVD, VEGF and efficacy. The relapsing rate was low in cases with low MVD, VEGF. No particular side effects were observed in thalidomide group. CONCLUSION: Anti-angiogenesis may decrease relapse and maintain recovery state of AL patients. There are no severe side effects in the thalidomide group.
