Hesperidin, a Citrus Bioflavonoid Potentiates Repair and Regeneration of Deep Dermal Excision Wounds of Mice Whole Body Exposed to Different Doses of 60Co γ-Radiation

Irradiation adversely affects the repair and regeneration of wounds causing negative impact on the clinical outcome. Therefore, it is necessary to screen newer paradigms that may help to mitigate the deleterious effects of ionizing radiations. Hesperidin (hesperitin-7-rhamnoglucoside or hesperitin-7-rutinoside), a predominant bioflavonoid found in citrus fruits has been evaluated for its wound healing activity in mice whole-body exposed to 2,4, 6 or 8 Gy of γ-radiation. A full-thickness skin wound was created on the dorsum of mice after exposure to various doses of γ-radiation and the wound repair and regeneration was assessed by capturing video images of the excision wounds periodically as a measure of wound contraction as well as by assessing the mean wound healing time. In addition, the biochemical profiles including collagen, hexosamine, DNA, and nitric oxide syntheses were estimated in the granulation tissues at various days postirradiation after exposure to 0 or 6 Gy. In a separate experiment histological information on fibroblast and blood vessel densities were collected in the regenerating granulation tissue at various post-irradiation days after 0 or 6 Gy irradiation. The whole-body exposure of mice to different doses of γ-radiation resulted in a dose dependent delay in the wound contraction and prolongation of wound healing time, where the highest delay was observed after 8 Gy irradiation. Administration of hesperidin orally before irradiation significantly reduced the radiation-induced delay in the wound contraction and mean wound healing time. The collagen, hexosamine, DNA and nitric oxide syntheses were significantly reduced after exposure to 6 Gy, whereas pretreatment with hesperidin significantly enhanced synthesis of collagen, hexosamine, DNA, and nitric oxide. Histological examination revealed an increased rise in fibroblast and vascular densities after treatment with hesperidin in comparison with 6 Gy irradiation. The study demonstrates that hesperidin treatment accelerated the healing of irradiated wounds by increasing the collagen, hexosamine, DNA, and nitric oxide syntheses and increasing the densities of fibroblasts and blood vessels in the regenerating wounds. The stimulation of a cascade of repair and regeneration processes by hesperidin could be a substantial therapeutic strategy in irradiated wounds.