PMID- 31439521
OWN - NLM
STAT- MEDLINE
DCOM- 20200706
LR  - 20200706
IS  - 1743-6109 (Electronic)
IS  - 1743-6095 (Linking)
VI  - 16
IP  - 10
DP  - 2019 Oct
TI  - Melatonin Treatment Ameliorates Hyperhomocysteinemia-Induced Impairment of 
      Erectile Function in a Rat Model.
PG  - 1506-1517
LID - S1743-6095(19)31280-9 [pii]
LID - 10.1016/j.jsxm.2019.07.003 [doi]
AB  - BACKGROUND: Hyperhomocysteinemia (HHcy) has been reported to be strongly 
      correlated with the occurrence of erectile dysfunction (ED), but the mechanisms 
      are not fully understood. Moreover, whether melatonin could be a potential 
      treatment of HHcy-induced ED needs to be elucidated. AIM: The aim of this study 
      was to investigate the effects of melatonin on HHcy-induced ED and the potential 
      mechanisms via modulating oxidative stress and apoptosis. METHODS: The 
      Sprague-Dawley (SD) rat model of HHcy was induced by 7% methionine (Met)-rich 
      diets. 36 male SD rats were randomly distributed into 3 groups (n = 12 per 
      group): control group, 7% Met group, and 7% Met + melatonin (Mel; 10 mg/kg, 
      intraperitoneal injection) treatment group. After 4 weeks, the erectile function 
      of all rats was evaluated by electrical stimulation of the cavernous nerve. 
      Histologic and molecular alterations of the corpus cavernosum were also analyzed 
      by immunofluorescence, immunohistochemistry, enzyme-linked immunosorbent assay, 
      Western blotting, and polymerase chain reaction. OUTCOMES: HHcy-induced ED rat 
      models were successfully established, and Mel could preserve erectile function 
      mainly through inhibiting oxidative stress via the Erk1/2/Nrf2/HO-1 signaling 
      pathway and suppression of apoptosis. RESULTS: Erectile function was 
      significantly reduced in the rats with HHcy compared with that in the control 
      group and was ameliorated in the HHcy rats treated with Mel. Compared with the 
      control group, the rats in the HHcy group showed the following: (1) higher levels 
      of total plasma homocysteine; (2) fewer neuronal nitric oxide synthase-positive 
      cells in the corpus cavernous; (3) higher levels of reactive oxygen species and 
      malondialdehyde, higher expression levels of nicotinamide adenine dinucleotide 
      phosphate oxidase, and lower activities of superoxide dismutase, indicating an 
      overactivated oxidative stress; (4) lower expression levels of Erk1/2/Nrf2/HO-1 
      signaling pathway components; and (5) higher levels of apoptosis, as determined 
      by the expression levels of Bax, Bcl-2, and caspase 3. Mel treatment improved the 
      erectile response, as well as histologic and molecular alterations. CLINICAL 
      TRANSLATION: Our study on a rodent model of HHcy provided evidence that Mel could 
      be a potential therapeutic method for HHcy-related ED. CONCLUSIONS: Mel treatment 
      improves erectile function in rats with HHcy probably by potential antioxidative 
      stress activity. This finding provides evidence for a potential new therapy for 
      HHcy-induced ED. Tang Z, Song J, Yu, Z, et al. Melatonin Treatment Ameliorates 
      Hyperhomocysteinemia-Induced Impairment of Erectile Function in a Rat Model. J 
      Sex Med 2019;16:1506-1517.
CI  - Copyright (c) 2019 International Society for Sexual Medicine. Published by Elsevier 
      Inc. All rights reserved.
FAU - Tang, Zhe
AU  - Tang Z
AD  - Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, Hubei, China; Institute of Urology, 
      Tongji Hospital, Tongji Medical College, Huazhong University of Science and 
      Technology, Wuhan, Hubei, China.
FAU - Song, Jingyu
AU  - Song J
AD  - Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, Hubei, China; Institute of Urology, 
      Tongji Hospital, Tongji Medical College, Huazhong University of Science and 
      Technology, Wuhan, Hubei, China.
FAU - Yu, Zhe
AU  - Yu Z
AD  - Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, Hubei, China; Institute of Urology, 
      Tongji Hospital, Tongji Medical College, Huazhong University of Science and 
      Technology, Wuhan, Hubei, China.
FAU - Cui, Kai
AU  - Cui K
AD  - Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, Hubei, China; Institute of Urology, 
      Tongji Hospital, Tongji Medical College, Huazhong University of Science and 
      Technology, Wuhan, Hubei, China.
FAU - Ruan, Yajun
AU  - Ruan Y
AD  - Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, Hubei, China; Institute of Urology, 
      Tongji Hospital, Tongji Medical College, Huazhong University of Science and 
      Technology, Wuhan, Hubei, China.
FAU - Wang, Tao
AU  - Wang T
AD  - Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, Hubei, China; Institute of Urology, 
      Tongji Hospital, Tongji Medical College, Huazhong University of Science and 
      Technology, Wuhan, Hubei, China.
FAU - Yang, Jun
AU  - Yang J
AD  - Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, Hubei, China; Institute of Urology, 
      Tongji Hospital, Tongji Medical College, Huazhong University of Science and 
      Technology, Wuhan, Hubei, China.
FAU - Wang, Shaogang
AU  - Wang S
AD  - Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, Hubei, China; Institute of Urology, 
      Tongji Hospital, Tongji Medical College, Huazhong University of Science and 
      Technology, Wuhan, Hubei, China.
FAU - Liu, Jihong
AU  - Liu J
AD  - Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, Hubei, China; Institute of Urology, 
      Tongji Hospital, Tongji Medical College, Huazhong University of Science and 
      Technology, Wuhan, Hubei, China. Electronic address: jhliu@tjh.tjmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190819
PL  - Netherlands
TA  - J Sex Med
JT  - The journal of sexual medicine
JID - 101230693
RN  - 0 (Antioxidants)
RN  - 0 (Biomarkers)
RN  - 0 (Reactive Oxygen Species)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 4Y8F71G49Q (Malondialdehyde)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 3.4.22.- (Casp3 protein, rat)
RN  - EC 3.4.22.- (Caspase 3)
RN  - JL5DK93RCL (Melatonin)
SB  - IM
MH  - Animals
MH  - Antioxidants/*pharmacology
MH  - Apoptosis/drug effects
MH  - Biomarkers/metabolism
MH  - Caspase 3/metabolism
MH  - Disease Models, Animal
MH  - Erectile Dysfunction/*drug therapy/etiology/physiopathology
MH  - Homocysteine/metabolism
MH  - Humans
MH  - Hyperhomocysteinemia/*complications
MH  - Male
MH  - Malondialdehyde/metabolism
MH  - Melatonin/*pharmacology
MH  - NADPH Oxidases/metabolism
MH  - Oxidative Stress/physiology
MH  - Penile Erection/drug effects
MH  - Penis/physiopathology
MH  - Random Allocation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/metabolism
MH  - Superoxide Dismutase/metabolism
OTO - NOTNLM
OT  - Apoptosis
OT  - Erectile Dysfunction
OT  - Hyperhomocysteinemia
OT  - Melatonin
OT  - Oxidative Stress
EDAT- 2019/08/24 06:00
MHDA- 2020/07/07 06:00
CRDT- 2019/08/24 06:00
PHST- 2019/05/08 00:00 [received]
PHST- 2019/06/18 00:00 [revised]
PHST- 2019/07/01 00:00 [accepted]
PHST- 2019/08/24 06:00 [pubmed]
PHST- 2020/07/07 06:00 [medline]
PHST- 2019/08/24 06:00 [entrez]
AID - S1743-6095(19)31280-9 [pii]
AID - 10.1016/j.jsxm.2019.07.003 [doi]
PST - ppublish
SO  - J Sex Med. 2019 Oct;16(10):1506-1517. doi: 10.1016/j.jsxm.2019.07.003. Epub 2019 
      Aug 19.