Quercetin-3-rutinoside protects against gamma radiation inflicted hematopoietic dysfunction by regulating oxidative, inflammatory, and apoptotic mediators in mouse spleen and bone marrow

Abstract

Radiation-induced hematopoietic dysfunction is one of the most common problems during unplanned radiation exposures and also in cancer patients receiving radiotherapy. Management of the hematopoietic system is necessary to promote survival against radiation. The present study was undertaken to demonstrate the protective potential of Quercetin 3 rutinoside (Q-3-R), against gamma radiation-induced hematopoietic injuries. C57BL/6 male mice exposed either to radiation or pretreated with Q-3-R (10 mg/kg body weight) were checked for hematopoietic protection using hematotoxicity indices, histopathological, and genotoxic evaluations. To elucidate the underlying mechanisms of Q-3-R mediated hematopoietic protection, oxidative/nitrosative stress, inflammatory and apoptotic markers as well as PCNA expression in spleen cross-sections were assessed. Studies revealed Q-3-R pretreatment inhibited radiation-induced ROS in spleen cells and better maintained the total antioxidant levels in serum that were otherwise altered post 7.5 Gy exposure. The NO levels and nitrotyrosine expression were also found inhibited by Q-3-R in the spleen. Differential regulations of Bcl2, Bax and NF-κB with reduced serum TNF-α level indicated anti-apoptotic and anti-inflammatory roles of Q-3-R. Q-3-R attenuated radiation mediated spleen damage by minimizing cell death and promoting proliferation. Restoration of abnormal histopathological changes in bone marrow following Q-3-R administration correlated to reduced apoptosis and altered cell cycle distributions. Chromosomal aberrations were also found reduced in Q-3-R pretreated bone marrow. Q-3-R restored the total leukocyte counts and serum IL-6 levels, further supporting its role in promoting hematopoiesis. These findings suggest that Q-3-R can potentially be used to minimize radiation inflicted hematopoietic toxicities during accidental as well as radiotherapy scenarios.

Keywords:

• Quercetin-3-rutinoside
• ionizing radiation
• hematopoietic system
• apoptosis
• rutin

Acknowledgements

The authors are grateful to Director, INMAS and Head, Division of Radiation Biodosimetry, INMAS for administrative supports. The supports from Dr. Ravi Soni, Dr. BG Roy and Ms. Namita Kalra, INMAS for facilitating irradiation, animal availability and flow cytometry studies are duly acknowledged. The authors would like to thank Mr. Akshay Kumar for technical assistance and support in animal studies. A Dahiya is recipient of DRDO junior research fellowship.

Disclosure statement

The authors declare no conflict of interest in the study.

Additional information

Funding

We acknowledge DRDO for funding the project [TD-15/INM313] and Director, INMAS for administrative support.