Mechanisms underlying the radioprotective effect of histamine on small intestine

Abstract

Histamine prevents radiation-induced toxicity by increasing proliferation of damaged intestinal mucosa and suppressing apoptosis that was associated with an increase in SOD and Catalase levels. This effect might be of clinical value in patients undergoing radiotherapy.

Enhancement of ionizing radiation response by histamine in vitro and in vivo in human breast cancer

“…3,4 In this regard, it was reported that histamine significantly protects small intestine and bone marrow, from high doses of ionizing radiation, in 2 models of rodents. [5][6][7] In addition, histamine has the ability to prevent ionizing radiation-induced functional and histological alterations of salivary glands. 8 These features make histamine a suitable candidate as a radioprotector for patients undergoing radiotherapy.…”

Histamine Receptors as Potential Therapeutic Targets for Cancer Drug Development

“…Histamine radioprotective effect on small intestine was related to an increased rate of proliferation as evidenced by the enhanced proliferation markers immunoreactivity [5-bromo-2'-deoxyuridine (BrdU), and proliferating cell nuclear antigen (PCNA)]. Additionally, this outcome was accompanied by a reduction in the number of apoptotic cells per crypt and a modification of antioxidant enzyme levels that could lead to enhance the antioxidant capacity of intestinal cells (Medina et al, 2007). Histamine also protects rat small intestine against ionising radiation damage and this effect was principally associated to a decrease in intestinal cell crypt apoptosis (Medina & Rivera, 2010a).…”

“…To summarize, histamine treatment can selectively modulate cellular damage produced by ionising radiation, thus preventing radiation induced damage on small intestine, bone marrow and salivary glands. Furthermore, histamine in vitro enhances the radiosensitivity of breast cancer cells (Medina et al, 2006) while does not modify that of melanoma (Medina et al, 2007). Despite histamine may be proliferative in some cancer cell types, it may still be beneficial as radioprotector in view of the fact that it is only administered for a short period of time to reduce the radiation induced damage.…”

“…During radiotherapy for intraabdominal and pelvic cancers, radiation seriously affects radiosensitive tissues such as small intestine and bone marrow (Erbyl et al, 2005;Hall & Giaccia, 2006). It was previously demonstrated that histamine treatment (daily subcutaneous injection, 0.1 mg.kg -1 ) significantly protects mouse small intestine against radiation-induced toxicity ameliorating histological injury and improving trophism of enterocytes (Medina et al, 2007). Histamine completely prevented the decrease in the number of crypts evoked by whole body irradiation, which is vital for small intestine restoration since the intestinal crypt contains a hierarchy of stem cells that preserve the potential to regenerate the stem cell population and the tissue after cytotoxic exposure (Potten et al, 2002).…”

Histamine and Breast Cancer: A New Role for a Well Known Amine

“…We have also proved that histamine prevents radiation-induced toxicity on small intestine by modulating the antioxidant enzymes expression and by suppressing apoptosis and increasing proliferation of damaged intestinal mucosa (Medina et al, 2007). Intracellular ROS concentration is critical for cell growth and survival; in normal cells ROS levels are kept low, but quite the opposite in tumor cells high levels of ROS close to the threshold of cytotoxicity are related to cell proliferation.…”