Effects of Tacrolimus (Prograf) on the Reproductive Efficiency of Mice
Main Article Content
Abstract
Tacrolimus is an immunosuppressant used after organ transplantation to prevent graft rejection. It involves long-term usage which may be associated with detrimental effects. This research aims to investigate the effects of Tacrolimus intake on the reproductive efficiency of mice. Tacrolimus was administered to the test group in doses of 0.5, 1.0, 2.0, and 3.0 mg/kg, while the control groups (positive and negative) were administered 1 ml/kg of distilled water and 20 % methanol, respectively. Reproductive parameters were measured following standard procedure. Male mice in the test group experienced a significant decrease (P<0.05) in their testes, epididymis, and sperm count compared to the control group. The oestrogen levels and gestation index of female mice in the test groups were significantly decreased (P<0.05) in a dose-dependent manner, along with the litter size and weight, in relation to the control group. However, the life birth index of mice did not vary significantly (P>0.05). There was a significant decrease (P<0.05) in the mean values of male and female reproductive parameters. This study has showcases that Tacrolimus capsule intake could cause reproductive organ malfunction and impair potency and fertility.
Downloads
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
How to Cite
References
Dadi X, Jinxiu G, Ruili D, Yanan L, Qingying S,Wenxiu H, Shan W, Ning W, Junjun M, Linlin W. The effect of tacrolimus-induced toxicity on metabolic profiling in target tissues of mice. BMC Pharmacol Toxicol. 2022; 23(1):87. doi: 10.1186/s40360-022-00626-x
Dagmara S, Aleksandra W, Joanna K, Agnieszka K, Jolanta W, Barbara W. The Effects of Short-Term Immunosuppressive Therapy on Redox Parameters in the Livers of Pregnant Wistar Rats. Int J Environ Res Public Health. 2019; 16(8):1370. doi: 10.3390/ijerph16081370
Nannan T, Jason MS, Richard EL, Dolores JL. Does Solid organ transplant affect male reproduction? Eur Urol Focus. 2018; 4(3):307-310.doi 10.1016/j.euf.2018.08.012
Xu LG, Yang YR, Wang HW, Qiu F, Peng WL, Xu HM, Han S, Liu Y, Tang LG, Fu J. Characteristics of male fertility after renal transplantation. Androl. 2011. 43 (3):203 207. DOI:10.1111/j.1439-0272.2010.01052.x
Kleinclauss F, Timsit MO, Thuret R. Sexuality, fertility and pregnancy after kidney transplantation. Prog Urol. 2016. 26(15):1122-1131. doi: 10.1016/j.purol.2016.08.014
Chang KT, Lin HY, Kuo CH, Hung CH. Tacrolimus suppresses atopic dermatitis-associated cytokines and chemokines in monocytes. J Microbiol. Immunol. Infect. 2016; 49(3):409-416. DOI:10.1016/j.jmii.2014.07.006
Kannegieter NM, Hesselink DA, Dieterich M, Kraaijeveld R, Rowshani AT, Leenen PJM, Baan CC. The Effect of Tacrolimus and Mycophenolic Acid on CD14+ Monocyte Activation and Function. PLoS One. 2017; 12(1):e0170806 DOI:10.1371/journal.pone.0170806
Igbokwe I, Echezonachi NP, Azubuike EP, Idowu CO. Evaluation of Acute and Sub-Chronic Toxicities and the Effect of Ointment Bases on the Antimicrobial Potency of the Ethanolic Extracts of Alchornea cordifolia Leaf and Terminalia superba Stem Bark, Trop.J Nat Prod Res. 2018; 2(7):370374. doi.org/10.26538/tjnpr/v2i7.12
Huang W, Mo L, Yang Y, Chen S, Liu Z, Ma Q, Luo X. Effect of Aspergillus fumigatus on infection in immunosuppressed rats. Ann Transpl Med. 2023; 11(2):88. doi: 10.21037/atm-22-6600
Lorke D. A new approach to tropical acute toxicity testing. Arch Toxicol. 1983; 54:275-287. DOI:10.1007/BF01234480
Lim-Sylinco CY, Ahian R, Blanco FR. Inhibitory effects of philoppine medicinal plants on germ cell genotoxicity of methylmethansulfonate, terracyclone and chloromycetin. Science Diliman. 1990; 3:1-7.
Ezumi MW, Amrah SS, Suhaimi AWM, Mohsin SSJ. Evaluation of the female reproductive toxicity of aqueous extract of Labisia pumila var. alata in rats. Ind J Pharmacol. 2007; 39(1):30-32. DOI: 10.4103/0253-7613.30760
Wyrobek AJ, Bruce ER. The induction of sperm shape abnormalities in mice and humans. In: Hollaender A, DeSerres FJ, editors. Chemical mutagens, Vol. 5: Principles and method for their detection. New York: Plenum; 1978.
Abayomi A. Book of Medical Laboratory Practice. 2007. 238 p.
Kurnatowska J, Banasiak M, Daniel P, Wagrowska DM, Nowicki M. Two cases of severe de novo colitis in kidney transplant recipients after conversion to prolonged-release Tacrolimus. Transpl Int. 2010; 23(5):553-558. DOI: 10.1111/j.1432-2277.2009.01009.x
Shaokui Chen, Ping Liao, Long Xi, Yang Yang, Wenzhong Wu, Md Sahidul Islam, Zibei Lin, Ying Zheng, Xin C. The Therapeutic Effect of Tacrolimus in a Mouse Psoriatic Model is Associated with the Induction of Myeloid-derived Suppressor Cells. Rheumatol Immunol Res. 2022; 3(4):190197. doi: 10.2478/rir-2022-0034
Lundy SD, Vij SC. Male infertility in renal failure and transplantation. Transl androl urol. 2019; 8(2):173181. https://doi.org/10.21037/tau.2018.07.16
Poormoosavi SM, Ghorbanzadeh B, Behmanesh MA, Ghobadi K, Amirgholami R. The Effect of Captopril and Losartan on Tacrolimus-Induced Testicular Toxicity in Rats. Shiraz E-Med J. 2021; 22(8):e106199. https://doi.org/10.5812/semj.106199.
Rodrigo OM, Mohadetheh M. Sex-Specific Responses to Tacrolimus and Mycophenolate Mofetil in Spontaneously Hypertensive Rats. Future Pharmacol. 2023; 3(4):862-876; https://doi.org/10.3390/futurepharmacol3040052
Kabat-Koperska J, Kolasa-Wołosiuk,J, Pilutin A, Safranow K, Kosik-Bogacka B, Baranowska-Bosiacka I, Gołembiewska E, Kędzierska E, Domański L, Ciechanowski K. Birth defects in juvenile Wistar rats after exposure to immunosuppressive drugs during pregnancy. Histol Histopathol. 2017; 32(1):43-55. doi:
14670/HH-11-769. Epub 2016 Apr 21.
Szypulska-Koziarska D, Wilk A, Marchelek-Myśliwiec M, Śleboda-Taront D, Wiszniewska B. Tacrolimus-Based Immunosuppressive Therapy Influences Sex Hormone Profile in Renal-Transplant Recipients- A Research Study. Biol. 2021; 10(8):709. doi: 10.3390/biology10080709
Fereshteh KF, HF, Ahmad A, Pejman M. The comparative effects of estrogen and tacrolimus on crushed sciatic nerve regeneration in male mice: functional and histopathological evaluation. Vet Res Forum. 2022; 13(2):241-247. doi: 10.30466/vrf.2020.135524.
Kabat-Koperska J, Kolasa-Wołosiuk A, Baranowska-Bosiacka I, Safranow K, Kosik-Bogacka D, Gutowska I, Pilutin A, Gołembiewska E, Kędzierska K, Ciechanowski K. The influence of exposure to immunosuppressive treatment during pregnancy on renal function and rate of apoptosis in native kidneys of female Wistar rats. Apoptosis. 2016; 21(11):1240-1248. doi: 10.1007/s10495-016-1281-y.
Grabowska M, Laszczyńska M, Kędzierska-Kapuza K, Kram A, Gill K, Piasecka M. The Effects of Long-Term Immunosuppressive Therapies on the Structure of the Rat Prostate. Int J Environ Res Public Health. 2020; 17(12):4614. doi: 10.3390/ijerph17124614.
Ghadimi M, Dashti-Khavidaki S, Shahali M, Gohari M, Khatami MR, Alamdari A. Tacrolimus interaction with oral oestrogen in kidney transplant recipients: A case-control study. J Clin Pharm Ther. 2018; 43(4):513518. https://doi.org/10.1111/jcpt.