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abstract

abstract

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Melatonin treatment improved erectile dysfunction via inhibiting oxidative stress and apoptosis in a hyperhomocysteinemia rat model

Tang, Z1; Cui, K1; Ruan, YJ1; Song, JY1; Wang, T 1; Yang, J1; Wang, SG1; Liu, JH2

1: Tongji Hospital, Tongji Medical College, HUST, China; 2: Tongji Hospital, Tongji Medical College, HUST, ChinaTongji Hospital, Tongji Medical College, HUST, China

Objective To investigate the effects of melatonin on rats with hyperhomocysteinemia (Hhcy)-related erectile dysfunction (HED), and the potential mechanisms via modulating oxidative stress and apoptosis.

Methods The rat model of hyperhomocysteinemia was induced by methionine-rich diet (7% methionine). Twelve rats fed a standard diet were regarded as a control group. Twenty-four rats were fed a methionine-rich diet. After a month, the rats with Hhcy were administered daily melatonin (n=12) in a dose of 10mg/kg or vehicle (n=12) intraperitoneally for 4 weeks. Rats as control group (n=12) were injected vehicle intraperitoneally for 4 weeks. Then, cavernous nerve electrostimulation was used to evaluate the erectile function of all rats. Total homocysteine (Hcy) levels in plasma were determined with ELISA. Fluorescent probe, ELISA and western blotting were performed to determine the levels of oxidative stress and related signaling pathway. TUNEL assay, RT-PCR and western blotting were performed to detect apoptosis.

Results Compared with the control group and the melatonin-treated group, the HED group showed (1) lower erectile function: lower intracavernosal pressure (ICP)/mean arterial pressure(MAP) ratio and lower total ICP (area under curve, AUC); (2) higher levels of total Hcy in plasma (3) higher levels of ROS and MDA, but lower levels of SOD activity; (4)higher expression levels of Erk1/2/Nrf2/HO1 signaling pathway than the control group, but lower levels than melatonin-treated group; (5) higher levels of apoptosis proved by the expression levels of Bax, Bcl-2, caspase 3 and apoptosis index.

Conclusion Melatonin supplementation improved erectile function in rats with Hhcy potentially via decreasing the levels of total Hcy, inducing protective effect through Erk1/2/Nrf2/HO1 signaling pathway against oxidative stress, and inhibiting apoptosis. This finding provides evidence for a potential therapy method for HED.

Disclosure:

Work supported by industry: no.

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