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Joseph Zenisek¹, S. Wolfe¹, B.D. Timmerberg¹, J.S. Tash¹, ¹Dept. of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS.

    The Bioastronautics Roadmap risks include unacceptable levels of tissue degeneration caused by occupational radiation exposure or the combined effects of radiation and other space flight factors. Hindlimb unloading in rats (HLS) is widely used to mimic many physiologic changes that occur during space flight. Previous work from our lab has demonstrated that long term HLS causes severe testicular atrophy and male sterility. More recent studies suggest that there is an inverse relation between age and the duration of HLS necessary to cause testicular degeneration. Reactive oxygen species (ROS) are a major factor in producing radiation and non-radiation induced apoptotic loss in the testis. We examined whether administration of the dietary ROS scavenger, alpha-lipoic acid (LA), could ameliorate HLS-induced testicular atrophy. HLS animals, and TO controls (tail harnessed and elevated, but with all limbs remaining in contact with the cage floor, and pair fed to HLS) were prepared as previously published, including partial ligation of the inguinal canal to prevent the testes from becoming abdominal during HLS. Animals were 12-13 wks old at the start of the study. After 10 wks of HLS, a 35% decline in testis weight and testis atrophy ranging from Sertoli cell-only like morphology with apparently normal interstitial histology, to total seminiferous and severe interstitial cell pyknosis were noted. On the other hand, LA (50 mg/day in the drinking water) resulted in retention of normal testicular histology and no decline in testis weight in HLS relative to TO and free roaming controls (FRC). LA had no significant effect on body weight gain during the 10 wk experiment within each treatment group. A problem noted in the long 10 wk duration of the HLS study, was the low n’s yielded in the HLS groups from loss of animals due to animals becoming unharnessed. Future studies will require re-harnessing at 5 wks while maintaining lack of hindlimb contact during re-harness for the HLS animals.

(Supported by NASA and NIH).