13-cis-Retinoic Acid Affects Brain Perfusion and Function: In Vivo Study

Abstract

Purpose. Study the effects of 13-cis-retinoic acid (13-RA), a synthetic analogue of a vitamin A used for the treatment of severe acne, on the blood flow in the rat brain using technetium-99m hexamethyl propylene amine oxime (99mTc-HMPAO) imaging. Methods. A total of 30 adult male Wistar rats were divided into the control (C), low-dose (L), and high-dose (H) groups. The L and H rats were exposed subcutaneously to 0.3 and 0.5 mg, respectively, of 13-RA per kg of body weight for seven days. Brain blood flow imaging was performed using a gamma camera. Then, a region of interest (ROI) around the brain (target, T), a whole-body region (WB), and a background region (BG) was selected and delimited. The net 99mTc-HMPAO brain counts were calculated as the net target counts, NTC=T−BG/WB−BG in all groups. At the end of the 99mTc-HMPAO brain blood flow imaging, the brain, heart, kidney, lung, and liver were rapidly removed, and their uptake was determined. Brain histopathological analysis was performed using hematoxylin and eosin stains. In addition, the plasma fatty acids were studied using gas chromatography/mass spectrometry. Results. There were highly significant differences between L and H in comparison to C and across the groups. The 99mTc-HMPAO radioactivity in the brain showed increased uptake in a dose-dependent manner. There were also significant changes in the brain tissues and decreased free fatty acids among the groups compared to C. Conclusion. 13-RA increases 99mTcHMPAO brain perfusion, uptake, and function and reduces fatty acids.