Lactobacillus supplementation prevents cisplatin-induced cardiotoxicity possibly by inflammation inhibition

Abstract

Purpose

Cardiotoxicity of chemotherapy exerts as the main hurdle for prognosis, while whether cisplatin causes severe cardiotoxicity remains largely unknown. Accumulating evidence reveals that intestinal microbiota functions importantly in nutrient metabolism and cardiovascular function. In this study, we observed the possible cardiotoxicity of cisplatin and explored the possible role of microbiota in the mouse model.

Methods

C57Bl6 mice were treated with 0, 3 or 6 mg/kg cisplatin via i.p. injection, together with or without Lactobacillus supplementation. Cardiac function was analyzed by echocardiography. Gut microbiota was analyzed by 16S RNA sequencing. Gene expression was analyzed by qPCR. The data differences were compared with Graphpad Prism 7.0.

Results

In comparison with the control group, 6 mg/kg per week cisplatin treatment for 3 weeks significantly decreased the body weight by about 33% (18.1 ± 2.1 vs 27.2 ± 0.9) and decreased the left ventricular ejection fraction by about 15% (0.57 ± 0.07 vs 0.67 ± 0.04). Together, the gut microbiota was found dramatically changed, manifested as 27% decrease of Firmicutes and increased pathological bacteria. Antibiotics treatment had no obvious beneficial effects on the body weight and cardiac function caused by cisplatin. However, Lactobacillus supplementation significantly increased the body weight and restored cardiac function, together with lower inflammation gene expression.

Conclusions

The study here has established a possible role of microbiota dysbiosis in cisplatin-associated toxic effects, while delivery of Lactobacillus would be beneficial for the cardiac function prevention possibly via inflammation control.

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