In previous studies we have demonstrated that 50 Hz, 100 μT magnetic field (MF) exposure of female Sprague‐Dawley rats for 13 weeks significantly enhances the development and growth of mammary tumors in a breast cancer model. The present study was designed to test the hypothesis that, at least in part, the tumor (co)promoting effect of MF exposure is due to MF effects on the immune surveillance system, which is of critical importance in protecting an organism against the development and growth of tumors. For this purpose, female Sprague‐Dawley rats of the same age as in the mammary tumor experiments were continuously exposed for different periods (2, 4, 8, and 13 weeks) to a 50 Hz, 100 μT MF. Control groups were sham‐exposed simultaneously. Following the different exposure periods, splenic lymphocytes were cultured and the proliferative responses to the T‐cell‐selective mitogen concanavalin A (Con A) and the B‐cell‐selective pokeweed mitogen (PWM) were determined. Furthermore, the production of interleukin‐1 (IL‐1) was determined in the splenocyte cultures. The mitogenic responsiveness of T cells was markedly enhanced after 2 weeks of MF exposure, suggesting a co‐mitogenic action of MF. A significant, but less marked increase in T‐cell mitogenesis was seen after 4 weeks of MF exposure, whereas no difference from sham controls was determined after 8 weeks, indicating adaptation or tolerance to this effect of MF exposure. Following 13 weeks of MF exposure, a significant decrease in the mitogenic responsiveness of lymphocytes to Con A was obtained. This triphasic alteration in T‐cell function (i.e., activation, tolerance, and suppression) during prolonged MF exposure resembles alterations observed during chronic administration of mild stressors, substantiating the hypothesis that cells respond to MF in the same way as they do to other environmental stresses. In contrast to T cells, the mitogenic responsiveness of B cells and IL‐1 production of PWM‐stimulated cells were not altered during MF exposure. The data demonstrate that MF in vivo exposure of female rats induces complex effects on the mitogenic responsiveness of T cells, which may lead to impaired immune surveillance after long‐term exposure. Bioelectromagnetics 19:259–270, 1998. © 1998 Wiley‐Liss, Inc.
Based primarily on the results of in vitro studies, it has been suggested that power-line (50 or 60 Hz) magnetic fields (MFs) may reduce immune function, which could lower resistance to infection or cancer. This study was conducted to evaluate the influence of acute and chronic in vivo exposure to a linearly polarized 50 Hz MF on immune function in female Sprague-Dawley rats. Groups of rats were exposed continuously to the MF at a flux density of 100 microT for periods of 3 days, 14 days or 13 weeks. For each exposure period, one control group of rats was sham-exposed together with each MF-exposed group. Experimental end points included analyses of T-lymphocyte subsets as well as other immune cells involved in cell-mediated immune responses, i.e. natural killer (NK) cells, B lymphocytes, macrophages, and granulocytes in blood, spleen and mesenteric lymph nodes. In addition, immunohistochemical methods were used to detect proliferating and apoptotic cells in the various compartments of spleen tissue. The results obtained failed to demonstrate a significant effect of short or prolonged MF exposure on different types of leukocytes, including lymphocyte subsets. Furthermore, the experiments on the in vivo proliferation activity of lymphocytes and the extent of apoptosis in spleen samples did not indicate a difference between the MF-exposed and sham-exposed groups, indicating that MF exposure does not affect the mechanisms involved in the control of lymphocyte homeostasis. The lack of MF effects in the immune tests used in the present in vivo study makes it highly unlikely that MF exposure induces immunotoxicity, at least under the experimental conditions used. However, the data do not exclude the possibility that functional alterations in T-cell responses to mitogens and in NK cell activity as recently described for MF-exposed rodents may be one mechanism involved in the carcinogenic effects of MF exposure observed in some models of co-carcinogenesis.
OBJECTIVES: The objectives of these studies were to investigate the toxicity, safety and toxicokinetics of single and multiple doses of artesunate for injection in rats and dogs. METHODS: Sprague-Dawley rats and Beagle dogs were treated intravenously or intramuscularly for 28 consecutive days with doses of up to 30 mg/kg artesunate, evaluating toxicity, kinetics, genotoxicity, and cardiovascular and central nervous safety parameters after single and 4-week repeated administrations. Furthermore, respiratory parameters were evaluated after a single intravenous administration in rats.RESULTS: Artesunate was well tolerated with no mortality and only minor effects on clinical pathology parameters. Following repeated intramuscular administration, local reactions at the injection site became evident. Signs of regenerative anaemia were evident in both rats and dogs and are attributed to the pharmacological effect of artesunate (effective against blood stages of malaria parasites). No severe toxicity or any effects on safety measures were noticed. CONCLUSIONS: The results obtained in these studies support the safe use of intravenous and intramuscular artesunate for a period beyond the commonly used three (to maximum seven) days in humans. Cardiovascular, central nervous and respiratory safety measures indicate no risk at clinically used doses.
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