MO Oxygen Therapy Prevents Doxorubicin-Induced Cardiotoxicity.

Abstract

Background: Micro-oxygen therapy can reduce the effects of doxorubicin (DOX) on left ventricular function, cardiac fibrosis, inflammation, and oxidative stress in SD rats. These results suggest the potential of DOX for clinical use. Method: 8-week-old SPF-grade SD male rats were randomly divided into four groups: control group (Ctrl) (n = 10), doxorubicin group (DOX) (n = 10), doxorubicin + conventional oxygen intervention group (DOX+CO) (n = 10), doxorubicin + micropressed oxygen group (DOX+MO)) (n = 10). Left ventricular function was assessed by echocardiography 3 weeks after the end of treatment, and histopathological analysis was conducted utilizing Masson and hematoxylin-eosin (HE) staining. The mRNA expression levels of TGF-β1 and Collagen I were quantified by quantitative real-time PCR (qRT-PCR). Additionally, inflammatory markers, including the concentrations of IL-1β, IL-6, and TNF-α, as well as the activities of SOD and GSH-Px, were measured using enzyme-linked immunosorbent assay (ELISA). Results: The DOX + MO group significantly improved the symptoms of heart failure caused by DOX. The specific results are as follows: The EF significantly increased to 78.037 ± 1.283 (63.259 ± 8.855 in the DOX, p ≤ 0.0001); the IVSs increased from 0.243 ± 0.036 to 0.324 ± 0.038 (p ≤ 0.001); the LVPWs increased from 0.263 ± 0.028 to 0.323 ± 0.036 (p ≤ 0.01); the IVSd and the LVPWd increased from 0.171 ± 0.019 to 0.2 ± 0.015 (p ≤ 0.05) and from 0.181 ± 0.032 to 0.234 ± 0.026 (p ≤ 0.01). Among cardiac function indexes, NT-proBNP in DOX + MO group was significantly different from that in DOX group (p ≤ 0.0001). Compared with DOX group, the degree of myocardial fibrosis in DOX + MO group was decreased, and qRT-PCR showed that MO oxygen effectively reduced the mRNA expression of TGF-β1 and collagen1 induced by DOX. In terms of inflammatory indicators, TNF-α (p ≤ 0.0001), IL-1β (p ≤ 0.0001), and IL-6 (p ≤ 0.0001) in DOX + MO group were significantly lower than those in DOX group. In terms of oxidative stress, serum levels of SOD and GSH-PX were decreased in the DOX group, and MO oxygen therapy effectively prevented the reduction of these indexes. On the other hand, the experimental results also showed that DOX + MO group was significantly better than DOX + CO group in terms of cardiac function, inflammation, and oxidative stress. Conclusion: Microbaric oxygen therapy can reduce the effects of DOX on left ventricular function, cardiac fibrosis, inflammation, and oxidative stress in SD rats. These results provide support for clinical studies to evaluate the potential of DOX in clinical applications.