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Published on: January 29, 2019
Early apoptotic response in kidney after 177Lu-octreotate administration with or without potential radioprotector
Charlotte Ytterbrink1,2, Klara Simonsson1,2, Emman Shubbar1,2
1Department of Medical Radiation Sciences, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden.
Abstract:
The antioxidant α1-microglobulin (A1M) has been suggested as kidney protector during 177Lu-octreotate treatment. The aim of this work was to evaluate apoptotic-related transcript expression in kidney cortex and medulla following injection of 177Lu-octreotate and/or A1M. Mice were injected with 177Lu-octreotate, A1M, or 177Lu-octreotate + A1M. Control groups received PBS or vehicle solution. Animals were killed after 24 hours or 7 d. mRNA was isolated from kidney medulla and cortex. Expression of 84 apoptosis-related genes was assessed by q-PCR. Gene expression profiles in kidney cortex were generally similar in the 177Lu-octreotate and 177Lu-octreotate + A1M groups. This was also seen in kidney medulla at 24 hours, but at 7 d anti-apoptotic response of A1M was observed. Altogether, 177Lu-octreotate exposure induced pro-apoptotic response (e.g. Apaf1, Bax, and Tnfrsf10b genes) in kidney medulla and cortex. A1M co-administration did not inhibit pro-apoptotic response in kidney cortex, while A1M initiated pro-survival mechanisms in kidney medulla.
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