Student Research: Ming-Chih Sun
MS, , 1993
The Effects of Dexamethasone and/or Captopril on the Dose Response for Radiation Nephropathy
The increasing use of radiation sources in industry, medicine and research has enhanced the risk of accidental whole-body exposure to ionizing radiation. Accidental human whole-body irradiation can result in death within 2 months from injury to the hematopoietic tissues and/or gastrointestinal mucosa. With the exception of lymphocytes, the mature functional curculating blood cells (neutrophils, platelets, red blood cells) are radioresistant. However, whole-body irradiation inhibits stem cell proliferation in these tissues, and therefore inhibition of normal replacement of functional cells when they reach the end of their life-spans. As a result, the dose required for lethality and the time of death reflect the radiosensitivity of the proliferating cells to mitotic death and the life-span of the functional cells, respectively.
Proliferating hematopoietic stem cells are among the most sensitive mammalian cells. Radiation doses of 4 to 10 Gy deplete hematopoietic stem cells to a level that is inadequate to maintain critical levels of circulating platelets (i.e., >5% of normal values) and neutrophils (i.e., >10% of normal values) necessary to combat hemorrhage and infection. Since the life-spans of neutrophils and paltelets are 2 to 3 weeks, it takes this long after irradiation to reach these critical levels. Death from infection and hemorrhage in humans occurs 3 to 6 weeks after exposure and coincides with maximum depletion of platelets and neutrophils.
The present investigation was carried out to evaluate postirradiation dexamethasone and/or captopril treatment on the radiation dose-response curve to determine if these treatments, singularly or combined, can reduce the severity of kidney injury. This study involves intraoperable localized exposure of the kidney to prevent acute hematopoietic and intestinal death and other confounding effects from radiation injuries to other organs. This information will be helpful in designing strategies to reduce kidney injury after accidental irradiation or planned radiation exposure in radiotherapy where the kidney is the critical normal tissue at risk.