cytochrome-c-t and hesperetin

To investigate whether hesperetin (Hes) alleviates doxorubicin (DOX)-induced cardiomyocytotoxicity by reducing oxidative stress via regulating silent information regulator 1 (SIRT1)/nuclear transcription factor E2-related factor 2 (NRF2) signaling in H9c2 cells.. H9c2 cells were treated with DOX to establish the cardiotoxicity model and were randomly assigned to four groups, a control group (Control) and three treatment groups, receiving respectively DOX (the DOX group), Hes+DOX (the DOX+Hes group), and Hes+SIRT1 inhibitor EX527+DOX (the DOX+Hes+EX527 group). Cellular morphology was observed by the light microscope. Cell viability was evaluated by CCK-8. DOX-induced apoptosis in H9c2 cells was examined by flow cytometry. The levels of reactive oxygen species (ROS) in the H9c2 cells of the four groups were determied with 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining. The activities of lactate dehydrogenase (LDH), superoxide dismutase (SOD), catalase (CAT), and SIRT1 as well as the malondialdehyde (MDA) content were measured using ELISA kits. The expressions of cleaved caspase-3, cytochrome c, SIRT1, Ac-FOXO1, NRF2, and heme oxygenase 1 (HO-1) were determined by Western blot.. Hes inhibits oxidative stress and apoptosis via regulating SIRT1/NRF2 signaling, thereby reducing DOX-induced cardiotoxicity in H9c2 cells.

Topics: Apoptosis; Cardiotoxicity; Caspase 3; Cytochromes c; Doxorubicin; Humans; Myocytes, Cardiac; NF-E2-Related Factor 2; Oxidative Stress; Reactive Oxygen Species; Sirtuin 1; Superoxide Dismutase

Doxorubicin (DOX) is one of the most widely used chemotherapeutic agents. However, it causes pulmonary toxicity which decreases its clinical use in human cancer therapy. The present study was undertaken to obtain an insight into the potential protective effect of hesperetin (HES) against doxorubicin-induced pulmonary toxicity in rats. The animals were divided into 4 groups with 7 rats per group. The experimental treatments were as follows: Control, DOX, DOX + HES, and HES groups. DOX was administered at the dosage of 15 mg/kg i.p for a single dose. HES was administered at the dosage of 50 mg/kg by oral gavage every other day. After 28 days, biochemical parameters, oxidative stress status, histopathological changes, apoptosis-related genes and apoptotic index (AI) were examined of lung tissue. Histopathological changes, Poly [ADP-ribose] polymerase 1 (PARP-1), Caspase-3 (Casp3), Cytochrome c (Cytc), apoptosis-related genes, and AI significantly increased in the DOX group relative to the control group. Malondialdehyde (MDA) significantly increased, while superoxide dismutase (SOD) and glutathione peroxidase (GPx) decreased in the DOX group relative to the control group. However, histopathological findings, MDA, AI, and PAPR1, Casp3 protein expression, mRNA expression of Cytc significantly decreased, while SOD, GPx increased in the DOX + HES group relative to the DOX group. These results attested HES might be a potential agent for the treatment of DOX-induced pulmonary toxicity.

Topics: Animals; Apoptosis; Body Weight; Caspase 3; Cytochromes c; Doxorubicin; Hesperidin; Lung; Male; Organ Size; Oxidative Stress; Poly(ADP-ribose) Polymerases; Rats, Sprague-Dawley; RNA, Messenger