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Abstract

Volume 23, Issue 3 (May 2021) 23, 249–258; 10.4103/aja.aja_69_20

The near-infrared dye IR-61 restores erectile function in a streptozotocin-induced diabetes model via mitochondrial protection

Xiao-Feng Yue1, Chong-Xing Shen1, Jian-Wu Wang1, Lin-Yong Dai1, Qiang Fang1, Lei Long2, Yi Zhi1, Xue-Ru Li3, Ya-Wei Wang2, Gu-Fang Shen2, Zu-Juan Liu2, Chun-Meng Shi2, Wei-Bing Li1

1 Department of Urology, The Third Affiliated Hospital of Chongqing Medical University (Gener Hospital), Chongqing 401120, China
2 Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing 400038, China
3 Department of Ophthalmology, The Third Affiliated Hospital of Chongqing Medical University (Gener Hospital), Chongqing 401120, China

Correspondence: Dr. WB Li (liweibing63@cqmu.edu.cn) or Dr. CM Shi (shicm@tmmu.edu.cn)

Date of Submission 22-Dec-2019 Date of Acceptance 06-Sep-2020 Date of Web Publication 01-Jan-2021

Abstract

This study aimed to evaluate the therapeutic effect of IR-61, a novel mitochondrial heptamethine cyanine dye with antioxidant effects, on diabetes mellitus-induced erectile dysfunction (DMED). Eight-week-old male Sprague–Dawley rats were intraperitoneally injected with streptozotocin (STZ) to induce type 1 diabetes. Eight weeks after STZ injection, all rats were divided into three groups: the control group, DM group, and DM + IR-61 group. In the DM + IR-61 group, the rats were administered IR-61 (1.6 mg kg−1) twice a week by intravenous injection. At week 13, erectile function was evaluated by determining the ratio of the maximal intracavernous pressure to mean arterial pressure, and the penises were then harvested for fluorescent imaging, transmission electron microscopy, histological examinations, and Western blot analysis. Whole-body imaging suggested that IR-61 was highly accumulated in the penis after intravenous injection. IR-61 treatment significantly improved the maximal ICP of diabetic rats. Additionally, IR-61 ameliorated diabetes-induced inflammation, apoptosis, and phenotypic transition of corpus cavernosum smooth muscle cells (CCSMCs) in penile tissue. IR-61 also attenuated mitochondrial damage, reduced reactive oxygen species production in the corpus cavernosum and upregulated sirtuin1 (SIRT1), sirtuin3 (SIRT3), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and heme oxygenase expression in penile tissue. In conclusion, IR-61 represents a potential therapeutic option for DMED by protecting the mitochondria of CCSMCs, which may be mediated by activation of the SIRT1, SIRT3, and Nrf2 pathways.

Keywords: corpus cavernosum smooth muscle cells; diabetes; erectile dysfunction; IR-61; mitochondria

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