Protective effect of sesamol against ⁶⁰Co γ-ray-induced hematopoietic and gastrointestinal injury in C57BL/6 male mice

Abstract

Protection of γ-ray-induced injury in hematopoietic and gastrointestinal (GI) systems is the rationale behind developing radioprotectors. The objective of this study, therefore, was to investigate the radioprotective efficacy and mechanisms underlying sesamol in amelioration of γ-ray-induced hematopoietic and GI injury in mice. C57BL/6 male mice were pre-treated with a single dose (100 or 50 mg/kg, 30 min prior) of sesamol through the intraperitoneal route and exposed to LD_50/30 (7.5 Gy) and sublethal (5 Gy) dose of γ-radiation. Thirty-day survival against 7.5 Gy was monitored. Sesamol (100 mg/kg) pre-treatment reduced radiation-induced mortality and resulted survival of about 100% against 7.5 Gy of γ-irradiation. Whole-body irradiation drastically depleted hematopoietic progenitor stem cells in bone marrow, B cells, T cell subpopulations, and splenocyte proliferation in the spleen on day 4, which were significantly protected in sesamol pre-treated mice. This was associated with a decrease of radiation-induced micronuclei (MN) and apoptosis in bone marrow and spleen, respectively. Sesamol pre-treatment inhibited lipid peroxidation, translocation of gut bacteria to spleen, liver, and kidney, and enhanced regeneration of crypt cells in the GI system. In addition, sesamol pre-treatment reduced the radiation-induced pattern of expression of p53 and Bax apoptotic proteins in the bone marrow, spleen, and GI. This reduction in apoptotic proteins was associated with the increased anti-apoptotic-Bcl-x and PCNA proteins. Further, assessment of antioxidant capacity using ABTS and DPPH assays revealed that sesamol treatment alleviated total antioxidant capacity in spleen and GI tissue. In conclusion, the results of the present study suggested that sesamol as a single prophylactic dose protects hematopoietic and GI systems against γ-radiation-induced injury in mice.

Keywords::

• sesamol
• γ-radiation
• hematopoietic progenitor stem cell
• bone marrow cells
• spleen
• gastro-intestine
• p53
• PCNA
• B cells
• CD4/CD8
• apoptosis

Acknowledgements

Shahanshah Khan is grateful to the Director, INMAS, Delhi, for providing work facility. The authors are also grateful to Dr. B G Roy for necessary animal facility, Mrs. Anjali Sharma for ⁶⁰Co γ-radiation source operation, and Mrs. Namita Kalra for flow cytometric analysis at INMAS. We thank Mr. Abdullah Farooque for the kind technical guidance in the lymphoproliferation assay using CFSE. CFSE was obtained from Mr. Abdulla Farooque as a kind gift. This work was supported by the Defence Research & Development Organization (DRDO) at the Institute of Nuclear Medicine and Allied Sciences (INMAS), as a project on “Development of Safe Chemical Radioprotector” (NBC 1.29).

Declaration of interest

The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.

Supplementary material available online

Supplementary Figure 1 to be found online at http://informahealthcare.com/doi/abs/10.3109/10715762.2015.1071485.