Effect and mechanism of androgens on mitochondrial functions of gastric mucosa in aged rats
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1.Department of Gastroenterology, Harrison International Peace Hospital, Hengshui 053000, China. 2. Hebei Yiling Hospital, Shijiazhuang 050000

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R-33

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    Abstract:

    Objective To investigate the effect and mechanism of androgens on mitochondrial functions of gastric mucosa in aged gonadectomized male (GDX) rats. Methods 36 male SD rats were randomly divided into three groups: sham operation group (Sham, n= 12), model group (GDX, n= 12) and androgen-supplemented model rats ( n= 12). GDX rats were used for modeling. After modeling, the AG group was administered testosterone ( 13. 6 mg / ( kg·d), dissolved in sesame seed oil). Rats in sham operation and model groups were treated with sesame seed oil. After the treatment, gastric tissue samples were collected and the levels of Mn-SOD, GSH-Px, GSH, GSSG, GSH/ GSSG and ROS in gastric mucosa mitochondria were measured by kits, the mitochondrial membrane potential was measured by rhodamine 123 fluorescence, and apoptosis was analyzed by flow cytometry. In vitro, GES-1 cells were used as the research object. H2O2 was used to induce cellular injury. The effects of androgens and ALDH2 inhibitor disulfiram on cell viability and apoptosis were investigated. Results Compared with Sham group, ROS and GSSG levels, gastric mucosal cell apoptosis and cleaved Caspase-3 and cytoplasmic Cyt c protein expression were significantly increased in the GDX group (P<0. 05), while Mn-SOD, GSH-PX, GSH and GSH/ GSSG levels, the mitochondrial membrane potential, ATP level and mitochondrial Cyt c and ALDH2 protein expression were decreased significantly (P<0. 05). After androgen treatment, the above changes in GDX elderly rats were reversed significantly ( P< 0. 05). In vitro, androgen treatment significantly reversed damage induced by H2O2 in GES-1 cells (P<0. 05). However, when combined with Disulfiram, the therapeutic activity of androgen was reduced significantly ( P< 0. 05). Conclusions Androgen deficiency leads to mitochondrial dysfunction and increased mitochondrial ROS accumulation in gastric mucosal cells of elderly rats and induces gastric mucosal cell apoptosis, which is at least partly related to inhibition of the antioxidant function of ALDH2.

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History
  • Received:November 17,2020
  • Revised:
  • Adopted:
  • Online: December 17,2021
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