Red-Fleshed Apple Flavonoids Extract Alleviates Male Reproductive Injury Caused by Busulfan in Mice

Overview

Journal Nutrients

Date 2023 Aug 12

PMID 37571225

Authors

Bin Wang

Yanbo Wang

Yizhou Chen

Xiaohong Sun

Jihua Xu

Jun Zhu

Yugang Zhang

Affiliations

Soon will be listed here.

Abstract

In this research, we analyzed the protective effects of red-fleshed apple flavonoid extracts (RAFEs) on male reproductive injury induced by busulfan, using both in vitro and in vivo models. In the cell-based experiments, RAFEs significantly improved cell viability and proliferation rates compared to control groups. Similarly, in vivo testing with male mice showed that RAFEs and whole apple flavonoid extracts (WAFEs) enhanced various biochemical and liver function-related indicators in the testes; however, RAFEs demonstrated superior efficacy in mitigating testicular damage. Through immunohistochemistry, qRT-PCR, and Western blotting, we found that RAFEs notably enhanced the expression of spermatogenesis-related genes. Moreover, RAFEs increased the expression of oxidative stress- and apoptosis-related genes, thereby effectively reducing oxidative damage in the testes. These findings highlight the potential of RAFEs as natural agents for the prevention and treatment of male reproductive injury, paving the way for future research and potential therapeutic applications.

References

Rak A, Mellouk N, Froment P, Dupont J . Adiponectin and resistin: potential metabolic signals affecting hypothalamo-pituitary gonadal axis in females and males of different species. Reproduction. 2017; 153(6):R215-R226. DOI: 10.1530/REP-17-0002. View

Chen G, Cao Z, Shi Z, Lei H, Chen C, Yuan P . Microbiome analysis combined with targeted metabolomics reveal immunological anti-tumor activity of icariside I in a melanoma mouse model. Biomed Pharmacother. 2021; 140:111542. DOI: 10.1016/j.biopha.2021.111542. View

Liu B, Fang Y, Yi R, Zhao X . Preventive Effect of Blueberry Extract on Liver Injury Induced by Carbon Tetrachloride in Mice. Foods. 2019; 8(2). PMC: 6406748. DOI: 10.3390/foods8020048. View

Alatrash G, Thall P, Valdez B, Fox P, Ning J, Garber H . Long-Term Outcomes after Treatment with Clofarabine ± Fludarabine with Once-Daily Intravenous Busulfan as Pretransplant Conditioning Therapy for Advanced Myeloid Leukemia and Myelodysplastic Syndrome. Biol Blood Marrow Transplant. 2016; 22(10):1792-1800. PMC: 5026955. DOI: 10.1016/j.bbmt.2016.06.023. View

Fang F, Ni K, Cai Y, Zhao Q, Shang J, Zhang X . Busulfan administration produces toxic effects on epididymal morphology and inhibits the expression of ZO-1 and vimentin in the mouse epididymis. Biosci Rep. 2017; 37(6). PMC: 5725615. DOI: 10.1042/BSR20171059. View

Wang B, Jiang S, Wang Y, Xu J, Xu M, Sun X . Red-Fleshed Apple Anthocyanin Extract Reduces Furan Content in Ground Coffee, Maillard Model System, and Not-from-Concentrate Apple Juice. Foods. 2021; 10(10). PMC: 8535902. DOI: 10.3390/foods10102423. View

Probin V, Wang Y, Zhou D . Busulfan-induced senescence is dependent on ROS production upstream of the MAPK pathway. Free Radic Biol Med. 2007; 42(12):1858-65. PMC: 1939827. DOI: 10.1016/j.freeradbiomed.2007.03.020. View

Amidzic Klaric D, Klaric I, Mornar A, Velic N, Velic D . Assessment of Bioactive Phenolic Compounds and Antioxidant Activity of Blackberry Wines. Foods. 2020; 9(11). PMC: 7694964. DOI: 10.3390/foods9111623. View

Wilhelmsson M, Vatanen A, Borgstrom B, Gustafsson B, Taskinen M, Saarinen-Pihkala U . Adult testicular volume predicts spermatogenetic recovery after allogeneic HSCT in childhood and adolescence. Pediatr Blood Cancer. 2014; 61(6):1094-100. DOI: 10.1002/pbc.24970. View

10.

Zhang X, Wang T, Deng T, Xiong W, Lui P, Li N . Damaged spermatogenic cells induce inflammatory gene expression in mouse Sertoli cells through the activation of Toll-like receptors 2 and 4. Mol Cell Endocrinol. 2012; 365(2):162-73. DOI: 10.1016/j.mce.2012.10.016. View

11.

Antolovich M, Prenzler P, Patsalides E, McDonald S, Robards K . Methods for testing antioxidant activity. Analyst. 2002; 127(1):183-98. DOI: 10.1039/b009171p. View

12.

Ceddia R, Somwar R, Maida A, Fang X, Bikopoulos G, Sweeney G . Globular adiponectin increases GLUT4 translocation and glucose uptake but reduces glycogen synthesis in rat skeletal muscle cells. Diabetologia. 2004; 48(1):132-9. DOI: 10.1007/s00125-004-1609-y. View

13.

Chi H, Chun K, Son H, Kim J, Kim G, Roh S . Effect of genistein administration on the recovery of spermatogenesis in the busulfan-treated rat testis. Clin Exp Reprod Med. 2013; 40(2):60-6. PMC: 3714430. DOI: 10.5653/cerm.2013.40.2.60. View

14.

Zhao Y, Zhang P, Ge W, Feng Y, Li L, Sun Z . Alginate oligosaccharides improve germ cell development and testicular microenvironment to rescue busulfan disrupted spermatogenesis. Theranostics. 2020; 10(7):3308-3324. PMC: 7053202. DOI: 10.7150/thno.43189. View

15.

Zhang X, Xu J, Xu Z, Sun X, Zhu J, Zhang Y . Analysis of Antioxidant Activity and Flavonoids Metabolites in Peel and Flesh of Red-Fleshed Apple Varieties. Molecules. 2020; 25(8). PMC: 7221745. DOI: 10.3390/molecules25081968. View

16.

Liu F, Dong W, Zhao H, Shi X, Zhang Y . Effect of molybdenum on reproductive function of male mice treated with busulfan. Theriogenology. 2018; 126:49-54. DOI: 10.1016/j.theriogenology.2018.12.002. View

17.

Ahles T, Saykin A . Candidate mechanisms for chemotherapy-induced cognitive changes. Nat Rev Cancer. 2007; 7(3):192-201. PMC: 3329763. DOI: 10.1038/nrc2073. View

18.

Dehghani F, Hassanpour A, Poost-Pasand A, Noorafshan A, Karbalay-Doust S . Protective effects of L-carnitine and homogenized testis tissue on the testis and sperm parameters of busulfan-induced infertile male rats. Iran J Reprod Med. 2014; 11(9):693-704. PMC: 3941323. View

19.

Li C, Zhao X, Zuo W, Zhang T, Zhang Z, Chen X . Phytochemical profiles, antioxidant, and antiproliferative activities of red-fleshed apple as affected by in vitro digestion. J Food Sci. 2020; 85(9):2952-2959. DOI: 10.1111/1750-3841.15358. View

20.

Zhao X, Hao H, Du W, Zhao S, Wang H, Wang N . Melatonin inhibits apoptosis and improves the developmental potential of vitrified bovine oocytes. J Pineal Res. 2015; 60(2):132-41. DOI: 10.1111/jpi.12290. View