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Astaxanthin Relieves Busulfan-Induced Oxidative Apoptosis in Cultured Human Spermatogonial Stem Cells by Activating the Nrf-2/Ho-1 Pathway Publisher Pubmed



Afzali A1 ; Amidi F1 ; Koruji M2 ; Nazari H3 ; Gilani MAS4 ; Sanjbad AS1
Authors
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Authors Affiliations
  1. 1. Department of Anatomy, School of Medicine, Medical School, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Stem Cell and Regenerative Medicine Research Center & Department of Anatomy, Iran University of Medical Sciences, Tehran, Iran
  3. 3. Research Institute of Animal Embryo Technology, Shahrekord University, Shahrekord, Iran
  4. 4. Department of Urology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: Reproductive Sciences Published:2022


Abstract

Many child cancer patients endure anticancer therapy containing alkylating agents before sexual maturity. Busulfan (BU), as an alkylating agent, is a chemotherapy drug, causing DNA damage and cytotoxicity in germ cells. In the present study, we aimed to investigate the protective effect of astaxanthin (AST), as a potent antioxidant and powerful reactive oxygen species (ROS) scavenger, on BU-induced toxicity in human spermatogonial stem cells. For this purpose, testes were obtained from four brain-dead donors. After tissue enzymatic digestions, testicular cells were cultured for 3 weeks for spermatogonial stem cell (SSC) isolation and purification. K562 cell line was cultured to survey the effect of AST on cancer treatment. The cultured SSCs and K562 cell line were finally treated with AST (10μM), BU (0.1nM), and AST+BU. The expression of NRF-2, HO-1, SOD2, SOD3, TP53, and apoptotic genes, including CASP9, CASP3, BCL2, and BAX, were assayed using real-time PCR. Moreover, ROS level in different groups and malondialdehyde level and total antioxidant capacity in cell contraction of SSCs were measured using ELISA. Data showed that AST significantly upregulated the expression of NRF-2 gene (P<0.001) and protein (P<0.005) and also significantly decreased the production of BU-induced ROS (P<0.001). AST activated the NRF-2/HO-1 pathway that could remarkably restrain BU-induced apoptosis in SSCs. Interestingly, AST upregulated the expression level of apoptosis genes in the K562 cell line. The results of this study indicated that AST reduces the side effects of BU on SSCs without interference with its chemotherapy effect on cancerous cells through modulation of the NRF-2/HO-1 and mitochondria-mediated apoptosis pathways. © 2021, Society for Reproductive Investigation.
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