The Effect of Astaxanthin After Varicocele Surgery on Antioxidant Status and Semen Quality in Infertile Men: A Triple-blind Randomized Clinical Trial

Overview

Journal Food Sci Nutr

Specialty Biotechnology

Date 2024 Oct 31

PMID 39479675

Authors

Shimal Ayub Mohammed Salih

Masoome Jabarpour

Mohammad Ali Sedighi Gilani

Hesamoddin Sajadi

Mojtaba Saedi Marghmaleki

Maryam Shabani Nashtaei

Maryam Salem

Fardin Amidi

Affiliations

Soon will be listed here.

Abstract

Varicocele (VC) is widely recognized as a prevalent etiological factor contributing to male infertility. It has been established that the generation of reactive oxygen species (ROS) plays a significant role in the progression and development of VC. Antioxidants may regulate ROS levels in these patients. Astaxanthin (ASX) is a carotenoid compound with notable antioxidant and anti-inflammatory characteristics. The current study postulated that the administration of ASX following varicocelectomy (VCT) could potentially enhance antioxidant status and semen quality in these patients. A total of 40 infertile males with clinical VC and abnormal semen analyses were randomly assigned to take part in the current trial. For 3 months following surgery, the intervention group took ASX (6 mg/day) while the control group received a placebo. After intervention, semen parameters, status, pro-inflammatory cytokines were compared between the two groups. Regarding semen parameters, antioxidant treatment led to a significant improvement in total and progressive motility in the treatment group ( < 0.05). Additionally, ASX led to a considerable increase in the expression levels of NRF2, Keap1, SOD2, SOD3, and BCL2, though the enhancement in the expression level of SOD3 was not statistically significant ( > .05). However, ASX significantly decreased the BAX expression level ( < .05). Even though the level of total antioxidant capacity (TAC) of seminal fluid (SF) increased significantly in the treatment group ( < .05), the level of total oxidative stress (TOS) in SF did not differ substantially between treatment and control groups ( > .05). Based on inflammatory factors in SF, ASX led to a considerable reduction in levels of TNF-α, IL-1β, and IL-6 ( < .05). Our findings demonstrated that ASX treatment provides an important contribution to VCT outcomes by modulating antioxidant status and pro-inflammatory cytokines. Our results indicated that ASX may be beneficial as an adjuvant therapy for infertile men following VCT.

References

Pereira C, Souza A, Vasconcelos A, Prado P, Name J . Antioxidant and anti‑inflammatory mechanisms of action of astaxanthin in cardiovascular diseases (Review). Int J Mol Med. 2020; 47(1):37-48. PMC: 7723678. DOI: 10.3892/ijmm.2020.4783. View

Fu J, Sun H, Wei H, Dong M, Zhang Y, Xu W . Astaxanthin alleviates spinal cord ischemia-reperfusion injury via activation of PI3K/Akt/GSK-3β pathway in rats. J Orthop Surg Res. 2020; 15(1):275. PMC: 7376638. DOI: 10.1186/s13018-020-01790-8. View

Moretti E, Collodel G, Mazzi L, Campagna M, Iacoponi F, Figura N . Resistin, interleukin-6, tumor necrosis factor-alpha, and human semen parameters in the presence of leukocytospermia, smoking habit, and varicocele. Fertil Steril. 2014; 102(2):354-60. DOI: 10.1016/j.fertnstert.2014.04.017. View

Lu J, Huang Y, Lu N . [WHO Laboratory Manual for the Examination and Processing of Human Semen: its applicability to andrology laboratories in China]. Zhonghua Nan Ke Xue. 2011; 16(10):867-71. View

Niture S, Jaiswal A . Nrf2 protein up-regulates antiapoptotic protein Bcl-2 and prevents cellular apoptosis. J Biol Chem. 2012; 287(13):9873-9886. PMC: 3323009. DOI: 10.1074/jbc.M111.312694. View

Sztretye M, Dienes B, Gonczi M, Czirjak T, Csernoch L, Dux L . Astaxanthin: A Potential Mitochondrial-Targeted Antioxidant Treatment in Diseases and with Aging. Oxid Med Cell Longev. 2019; 2019:3849692. PMC: 6878783. DOI: 10.1155/2019/3849692. View

Liu Y, Yang H, Wen Y, Li B, Zhao Y, Xing J . Nrf2 Inhibits Periodontal Ligament Stem Cell Apoptosis under Excessive Oxidative Stress. Int J Mol Sci. 2017; 18(5). PMC: 5454985. DOI: 10.3390/ijms18051076. View

Lee O, Jain A, Papusha V, Jaiswal A . An auto-regulatory loop between stress sensors INrf2 and Nrf2 controls their cellular abundance. J Biol Chem. 2007; 282(50):36412-20. DOI: 10.1074/jbc.M706517200. View

Bi J, Cui R, Li Z, Liu C, Zhang J . Astaxanthin alleviated acute lung injury by inhibiting oxidative/nitrative stress and the inflammatory response in mice. Biomed Pharmacother. 2017; 95:974-982. DOI: 10.1016/j.biopha.2017.09.012. View

10.

Hassanin A, Ahmed H, Kaddah A . A global view of the pathophysiology of varicocele. Andrology. 2018; 6(5):654-661. DOI: 10.1111/andr.12511. View

11.

Fassett R, Coombes J . Astaxanthin: a potential therapeutic agent in cardiovascular disease. Mar Drugs. 2011; 9(3):447-65. PMC: 3083660. DOI: 10.3390/md9030447. View

12.

Naguib Y . Antioxidant activities of astaxanthin and related carotenoids. J Agric Food Chem. 2000; 48(4):1150-4. DOI: 10.1021/jf991106k. View

13.

Smith R, Kaune H, Parodi D, Madariaga M, Rios R, Morales I . Increased sperm DNA damage in patients with varicocele: relationship with seminal oxidative stress. Hum Reprod. 2005; 21(4):986-93. DOI: 10.1093/humrep/dei429. View

14.

Khan N, Ahmad I, Haqqi T . Nrf2/ARE pathway attenuates oxidative and apoptotic response in human osteoarthritis chondrocytes by activating ERK1/2/ELK1-P70S6K-P90RSK signaling axis. Free Radic Biol Med. 2018; 116:159-171. PMC: 5815915. DOI: 10.1016/j.freeradbiomed.2018.01.013. View

15.

Zeinali M, Hadian Amree A, Khorramdelazad H, Karami H, Abedinzadeh M . Inflammatory and anti-inflammatory cytokines in the seminal plasma of infertile men suffering from varicocele. Andrologia. 2016; 49(6). DOI: 10.1111/and.12685. View

16.

Eslami M, Esfandyari S, Aghahosseini M, Rashidi Z, Hosseinishental S, Brenjian S . Astaxanthin Protects Human Granulosa Cells against Oxidative Stress through Activation of NRF2/ARE Pathway and Its Downstream Phase II Enzymes. Cell J. 2021; 23(3):319-328. PMC: 8286460. DOI: 10.22074/cellj.2021.7222. View

17.

Said T, Agarwal A, Sharma R, Thomas Jr A, Sikka S . Impact of sperm morphology on DNA damage caused by oxidative stress induced by beta-nicotinamide adenine dinucleotide phosphate. Fertil Steril. 2005; 83(1):95-103. DOI: 10.1016/j.fertnstert.2004.06.056. View

18.

Ardestani Zadeh A, Arab D, Sadat Kia N, Heshmati S, Amirkhalili S . The role of Vitamin E - Selenium - Folic Acid Supplementation in Improving Sperm Parameters After Varicocelectomy: A Randomized Clinical Trial. Urol J. 2019; 16(5):495-500. DOI: 10.22037/uj.v0i0.4653. View

19.

Choi H, Kim J, Chang M, Kyu-Youn Y, Shin W . Effects of astaxanthin on oxidative stress in overweight and obese adults. Phytother Res. 2011; 25(12):1813-8. DOI: 10.1002/ptr.3494. View

20.

Karna K, Choi B, Kim M, Kim H, Park J . The Effect of Schisandra chinensis Baillon on Cross-Talk between Oxidative Stress, Endoplasmic Reticulum Stress, and Mitochondrial Signaling Pathway in Testes of Varicocele-Induced SD Rat. Int J Mol Sci. 2019; 20(22). PMC: 6888522. DOI: 10.3390/ijms20225785. View