ABSTRACT
Background: Aegle marmelos (A. marmelos), a medicinal herb, is widely used in the Indian system of medicine for treatment of various ailments. The methanolic extract of A. marmelos leaves had shown antioxidant effect. However, so far aqueous extract of A. marmelos is not scientifically evaluated for its cardio protective potential. Hence the present study was designed to find out cardio protective role of A. marmelos against doxorubicin induced cardiotoxicity.Methods: Thirty rats were randomized into five major groups (n=6). Group I received only 2ml/100g/day normal saline p.o., group II received 2ml/100g/day of normal saline p.o. followed by doxorubicin on 21st day, group III received carvedilol 30 mg/kg/day p.o., Group IV received A. marmelos 250mg/kg/day p.o. and Group V received A. marmelos 500mg/kg/day p.o. for 21days. Doxorubicin 20mg/kg i.p. single dose was given to induce cardiotoxicity in rats of group II, III, IV and V respectively on last day of experiment. Animals were sacrificed 48 hours after doxorubicin administration. Cardiac serum markers creatinine phosphokinase MB, lactate dehydrogenase, serum glutamate oxaloacetate transaminase and serum glutamate pyruvate transaminase were analysed biochemically. Histopathological changes were studied under light microscope.Results: All cardiac serum marker levels were found significantly (p<0.001) increased in doxorubicin group while A. marmelos pre-treated group displayed significant (p<0.001) reduction in rise of these parameters in a dose dependent manner indicating cardio protection. Histological observations further correlated the cardio protective effect of A. marmelos.Conclusions: The present study concluded that aqueous extract of A. marmelos possesses cardio protective potential against doxorubicin induced cardiotoxicity.
ABSTRACT
Objective To detect the protein expression changes of mitochondrial apoptotic pathway during the reverse effects of lipid emulsion on bupivacaine cardiotoxicity, so as to investigate the probable mechanism concerning the reverse effect of lipid emulsion on bupivacaine cardiotoxicity.Methods The ventricular muscles of 15 healthy SD neonatal mice (1-3 d) were chosen to conduct primary culture in vitro.And the cardiomyocytes were cultivated in a medium containing bupivacaine for 24 hours to establish its bupivacaine poisoning model.The cultured cardiomyocytes were divided into three groups: control group (group C);bupivacaine group (group B);and bupivacaine+lipid emulsion group (group BL).Flow cytometry was applied to examine the apoptosis of cardiomyocytes, and the Western blot was employed to detect the protein expression variation of cytochrome C (Cyto-C) and cleaved casepase-3.Results Compared with group C, the apoptosis rate was remarkably increased in both group B and group BL and that of the group B was dramatically higher than that of the group BL, with a statistical significance (P<0.05).Compared with group C, the protein expression levels of both Cyto-C and cleaved casepase-3 were significantly increased in groups B and BL (P<0.05), and the protein expression levels of both Cyto-C and cleaved casepase-3 in group B were significantly higher than those in group BL (P<0.05).Conclusion Lipid emulsion can regulate apoptosis through inhibiting the release of mitochondrial Cyto-C and reducing casepase-3 activation, thus it protects cardiomyocytes.
ABSTRACT
Objective: To explore the role of calcium/calmodulin-dependent protein kinase-II δ (CaMK-II δ) in doxorubicin (DOX) induced cardio-toxicity in experimental rats. Methods:①The rat’s cardiomyocytes were treated by DOX and the cell proliferation, protein expression and activity of CaMK-II δ were examined.②CaMK-II δ gene was knocked out by CRISPR method, the changes of DOX induced cell apoptosis and NF-κb activity and miR-146a expression were detected. Results: DOX could inhibit cardiomyocyte proliferation, the protein expression level of CaMK-II δ was similar and the activity was increased. CRISPR method may effectively knock out CaMK-II δ gene. Compared with normal cells, the cells from CaMK-II δ knocked out rats had decreased sensitivity to DOX induction, suppressed NF-κb activation and miR-146a up-regulation. Conclusion: CaMK-II δ participated in DOX induced cardio-toxicity in experimental rats and NF-κb and miR-146a were involved in this process.