Study on ferroptosis pathway that operates in hypertensive brain damage

ABSTRACT

Objective

This study aimed to explore the mechanism of hypertensive brain damage from ferroptosis pathway.

Methods

Ten 22-week-old SHR rats were labeled as hypertension group(HBP), while ten WKY rats of comparable age, weight were used as normal blood pressure group(NBP). After 2 weeks of feeding, hypertensive brain damage was observed by comparing the pathological changes of brain tissue in SHR rats and WKY rats. Furthermore, the expression of GPX4 in the cerebral cortex was detected by immunofluorescence. The content of GSH was determined by spectrophotometer. The content of iron was detected by ferrous chromite colorimetry. And the content of MDA was determined by spectrophotometer. Compare the difference to investigate the role of ferroptosis mechanism in hypertensive brain damage.

Results

Brain damage occurred in 24-week-old SHR rats compared with WKY rats. In the HBP, the GPX4 and GSH were significantly lower than those in the NBP, and the total iron content and MDA were significantly increased.

Conclusion

Thses findings suggest ferroptosis is closely related to hypertensive brain damage. Elevated blood pressure leads to iron overload in the brain. Excessive iron increases oxidative stress and lipid peroxidation in the brain, and eventually causes brain damage.

KEYWORDS:

• Ferroptosis
• hypertension
• brain damage
• GPX-4
• GSH
• MDA
• iron

Authors’ contribution

YJ and GY carried out the animal studies, participated in collection and analyze of data and drafted the manuscript. WM and LGP carried out the collection of data and performed the statistical analysis. WS participated in the design of the study and helped to draft the manuscript. All authors read and approved the final manuscript.

Acknowledgments

We are grateful to ZHANG Siwen for providing assistance in the experiment. We also thank the support of the Science and Technology Development Fund of Tianjin Education Commission for Higher Education (2017KJ146, 2017KJ147) and Tianjin Applied Basic and Frontier Technology Research Program (17JCYBJC25900).

Competing interest reposition

The author(s) declare that they have no competing interests.

Additional information

Funding

Supported by the Science and Technology Development Fund of Tianjin Education Commission for Higher Education [2017KJ146, 2017KJ147] and Tianjin Applied Basic and Frontier Technology Research Program [17JCYBJC25900].