The cardiotoxicity of pirarubicin (THP) seriously affects its clinical application, which cannot be ignored. The antioxidant effect of schisandrin B (SchB) has been extensively reported in the context of dietotherapy. However, whether this antioxidant effect can protect the heart from THP damage remains unknown. The aim of the present study was to investigate whether the antioxidant effect of SchB can antagonize the cardiotoxicity of THP. Changes in electrocardiogram (ECG), echocardiography and serum lactate dehydrogenase, brain natriuretic peptide, creatine kinase MB and cardiac troponin T levels were used to detect the degree of cardiac damage. The levels of superoxide dismutase (SOD), malondialdehyde, catalase and total antioxidant capacity in the serum and heart were measured to observe the oxidative stress state of rats. Primary cardiomyocytes were cultured, and cell viability and reactive oxygen species (ROS) production were detected. Western blotting was used to detect the expression levels of SOD2, NOX2, pro/cleaved-caspase3 and Bcl-2/Bax in heart tissue and primary cardiomyocytes to verify the related signaling pathways. THP-treated rats showed a range of cardiac damage, including an abnormal ECG, echocardiography and myocardial enzymes. In the cellular experiments, cell viability decreased and ROS increased. However, this damage was alleviated after SchB treatment. Further studies demonstrated that SchB antagonized THP cardiotoxicity via its antioxidant effect. In conclusion, SchB protects the heart from THP damage in rats, and the mechanism may be closely associated with its antioxidant effect.
Doxorubicin (DOX) has powerful anticancer properties, but its clinical application is affected by its serious cardiotoxicity. Wogonin (WG) has been shown to have marked cardiovascular protection potential. However, it is not known whether this potential can protect the heart from DOX damage. The aim of the present study was to investigate whether WG could ameliorate the cardiotoxicity of DOX. DOX and WG were used to establish a model of cardiac damage. Echocardiography, brain natriuretic peptide, creatine kinase MB and cardiac troponin T were used to detect the degree of cardiac damage. The levels of superoxide dismutase, malondialdehyde, glutathione and catalase in serum were measured to observed oxidative stress state. The mRNA levels of cyclophilin D, voltage-dependent anion-selective channel 1 and adenine nucleotide transporter 1 were detected by reverse transcription-quantitative PCR. Western blotting was used to detect the expression of cytochrome c in mitochondria and cytoplasm and cleaved-caspase-9 and pro/cleaved-caspase-3 in cytoplasm in cardiac tissue and primary cardiomyocytes to verify the related signaling pathways. DOX rats showed a series of cardiac damage. However, these damages were alleviated following WG treatment. Further studies showed that WG antagonized DOX cardiotoxicity through inhibiting the release of cytochrome c. WG protected rat heart from DOX damage. The mechanism may be closely related to inhibiting the release of cytochrome c from mitochondria and reducing cardiomyocyte apoptosis caused by caspase activation.
Epilepsy is a common chronic neurological disorder worldwide. MicroRNAs (miRNAs) play an important role in the pathogenesis of epilepsy. However, the mechanism of the regulatory effect of miR-10a on epilepsy is unclear. In this study, we investigated the effect of miR-10a expression on the PI3K/Akt/mTOR signaling pathway and inflammatory cytokines in epileptic hippocampal neurons of rats. The miRNA differential expression profile of rat epileptic brain was analyzed using bioinformatic approaches. Neonatal Sprague–Dawley rat hippocampal neurons were prepared as epileptic neuron models in vitro by replacing culture medium with magnesium-free extracellular solution. The hippocampal neurons were transfected with miR-10a mimics, and transcript levels of miR-10a, PI3K, Akt and mTOR were detected by quantitative reverse transcription-PCR, and PI3K, mTOR, Akt, TNF-α, IL-1β, IL-6 protein expression levels were detected by Western blot. Cytokines secretory levels were detected by ELISA. Sixty up-regulated miRNAs were identified in the hippocampal tissue of epileptic rats and might affect the PI3K-Akt signaling pathway. In the epileptic hippocampal neurons model, the expression levels of miR-10a were significantly increased, with decreasing levels of PI3K, Akt and mTOR, and increasing levels of TNF-α, IL-1β and IL-6. The miR-10a mimics promoted the expression of TNF-α, IL-1β and IL-6. Meanwhile, miR-10a inhibitor activated PI3K/Akt/mTOR pathway and inhibited cytokines secretion. Finally, cytokine secretion was increased by treated with PI3K inhibitor and miR-10a inhibitor. The miR-10a may promote inflammatory responses in rat hippocampal neurons by inhibiting the PI3K/Akt/mTOR pathway, suggesting that miR-10a may be one of the target therapeutic molecules for epilepsy treatment.
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