Micheliolide Protects Against Doxorubicin-Induced Cardiotoxicity in Mice by Regulating PI3K/Akt/NF-kB Signaling Pathway
CARDIOVASCULAR TOXICOLOGY
Authors: Kalantary-Charvadeh, Ashkan; Sanajou, Davoud; Hemmati-Dinarvand, Mohsen; Marandi, Yasser; Khojastehfard, Mehran; Hajipour, Hamed; Mesgari-Abbasi, Mehran; Roshangar, Leila; Ahmad, Saeed Nazari Soltan
Abstract
Micheliolide (MCL) is a naturally derived anti-inflammatory agent. In the present investigation, we examined the protective potential of MCL against doxorubicin (DOX)-induced cardiotoxicity in mice. Mice were injected with a single 15-mg/kg intraperitoneal dose of DOX at day 1 and the study groups received daily 12.5, 25, and 50 mg/kg doses of MCL for 7 days. Cardiac histopathology, cardiac function, serum markers of cardiac injury, and tissue markers of inflammation, and oxidative stress were examined. MCL decreased serum levels of creatinine kinase MB (CK-MB) and cardiac troponin I (cTnI) levels, ameliorated cardiac tissue architecture, and improved cardiac stroke volume. Apart from reducing the activities of NF-kB p65 subunit, MCL attenuated the cardiac levels of PI3K, phosphorylated (p)-Akt, p-Bad, and caspase-3 levels and simultaneously elevated p-PTEN levels. While the gene expressions of tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) were decreased, the tissue activities of superoxide dismutase (SOD) as well as gene expressions of heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase-1 (NQO1) were increased after treatment with MCL. Furthermore, tissue levels of malondialdehyde (MDA) were also decreased. Collectively, these findings point to the protective effects of MCL against DOX-induced cardiotoxicity by regulating PI3K/Akt/NF-kB signaling pathway in mice.
The efficacy observation of ulinastatin combined with creatine phosphate sodium in pediatric viral myocarditis
EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES
Authors: Li, C-L; Jia, L-B; Gao, J.; Wang, Z-Z; An, X. J.
Abstract
OBJECTIVE: This study aimed to compare the efficacy and safety of ulinastatin combined with creatine phosphate sodium and ribavirin combined with creatine phosphate sodium in the treatment of pediatric viral myocarditis. PATIENTS AND METHODS: 155 children with viral myocarditis in the Xuzhou Children's Hospital, were retrospectively analyzed. 80 of them received ulinastatin combined with creatine phosphate sodium, and were regarded as observation group; other 75 patients received ribavirin combined with creatine phosphate sodium, and were regarded as the control group. The therapeutic efficacy of the two groups was observed, the improvement condition of myocardial enzyme indicator and myocardial troponin I (cTn I) in the two groups were compared before and after the treatment. RESULTS: The total effective rates of the patients in the observation group and the control group were 93.75% and 76.00%, respectively. The clinical efficacy of the observation group was better than that of the control group (p<0.05). The electrocardiogram improvement condition of the observation group was better than that of the control group (p<0.05): after the treatment, the expression levels of lactate dehydrogenase (LDH), aspartate aminotransferase (AST), Creatine Kinase (CK-MB), and cTn I in the observation group were (313.37 +/- 9.42) U/L, (29.38 +/- 4.97) U/L, (23.67 +/- 2.89) U/L, (0.12 +/- 0.02) mu g/L. respectively. The expression levels of LDH. AST, CK-MB, and cTn I in the control group were (322.43 +/- 12.32) U/L, (33.43 +/- 5.14) U/L, (26.22 +/- 3.37) U/L, (0.24 +/- 0.04) mu g/L. The levels of myocardial enzyme and cTn I in the observation group and the control group after the treatment were lower than that before the treatment (p<0.05), while the level of myocardial enzyme and cTn I in the observation group after the treatment was significantly lower than that in the control group (p<0.05). CONCLUSIONS: The results indicated that. compared with ribavirin combined with creatine phosphate sodium. ulinastatin combined with creatine phosphate sodium had better clinical efficacy in the treatment of pediatric viral myocarditis. It could significantly improve the level of myocardial enzyme indicator and cTn I, and had certain clinical and promotional values and application values.