Protective Effect of Aloe vera Gel against Cisplatin-Induced Testicular Damage, Sperm Alteration and Oxidative Stress in Rats

Document Type : Original Article

Authors

1 Department of Basic Sciences, Histology Section, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran

2 Stem Cell and Transgenic Technology Research Center, Department of Basic Sciences, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran

3 Department of Basic Sciences, Division of Biochemis try and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran

Abstract

Background:
Cisplatin is an effective antineoplastic drug that is used to treat varioustypes of cancers. However, it causes side effects on the male reproductive system. The present study aimed to investigate the possible protective effects of Aloe vera gel (known as an antioxidant plant) on cisplatin-induced changes in rat spermparameters, testicular structure, and oxidative stress markers.
Materials and Methods:
In this experimental study, forty-eight adult male rats were divided into 6 groups including: control, cisplatin (CIS), A. vera (AL), metformin (MET), cisplatin+A. vera (CIS-AL), and cisplatin+metformin (CIS-MET). Cisplatin was used intraperitoneally at a dose of 5 mg/kg on days 7, 14, 21, and 28 of the experiment. A. vera gel (400 mg/kg per day) and metformin (200 mg/kg per day) were administered orally for 35 days (started one week before the beginning of the experiment). Testes weight and dimensions, and morphometrical and histological alterations, activities of antioxidant enzymes including superoxide dismutase (SOD) and glutathione peroxidase (GPx), serum testosterone concentration, lipid peroxidation level, and sperm parameters were examined.
 
Results:
Cisplatin caused a significant decrease (p <0.05) in relative weight and dimension of the testis, germinal epithelium thickness and diameter of seminiferoustubules, the numbers of testicular cells, and spermatogenesis indexes.The malondialdehyde (MDA) levels increased and antioxidant enzymes activities decreased in the CIS group compared to the control group (p <0.05). Additionally, sperm parameters (concentration, viability, motility, and normal morphology), and testosterone levels reduced significantly in cisplatin-treated rats (p <0.05). Also, cisplatin induced histopathological damages including disorganization, desquamation, atrophy, and vacuolation in the testis. However, administration of A. vera gel to cisplatin-treated rats attenuated the cisplatin-induced alterations, mitigated testicular oxidative stress and increased testosterone concentration.
 
Conclusion:
The results suggest that A. vera as a potential antioxidant plant and due to free radicals scavenging activities, has a protective effect against cisplatin-induced testicular alterations.

Keywords


1. Ghosh S. Cisplatin: The firs t metal based anticancer drug. Bioorg Chem. 2019; 88: 102925.
2. Ijaz MU, Tahir A, Samad A, Ashraf A, Ameen M, Imran M, et al. Cas ticin alleviates tes ticular and spermatological damage induced by cisplatin in rats. Pak Vet J. 2020; 40 (2): 234-238.
3. Zhang X, Yamamoto N, Soramoto S, Takenaka I. Cisplatin-induced germ cell apoptosis in mouse tes tes. Arch Androl. 2001; 46(1): 43-49.
4. Azarbarz N, Shafiei Seifabadi Z, Moaiedi MZ, Mansouri E. Assessment of the effect of sodium hydrogen sulfide (hydrogen sulfide donor) on cisplatin-induced tes ticular toxicity in rats. Environ Sci Pollut Res Int. 2020; 27(8): 8119-8128.
5. Almeer RS, Abdel Moneim AE. Evaluation of the protective effect of olive leaf extract on cisplatin-induced tes ticular damage in rats. Oxid Med Cell Longev. 2018: 8487248.
6. Hamza AA, Elwy HM, Badawi AM. Fenugreek seed extract attenuates cisplatin-induced tes ticular damage in Wis tar rats. Andrologia. 2016; 48(2): 211-221.
7. Sánchez M, González-Burgos E, Iglesias I, Gómez-Serranillos MP. Pharmacological update properties of Aloe vera and its major active cons tituents. Molecules. 2020; 25(6): 1324.
8. Bala S, Chugh NA, Bansal SC, Garg ML, Koul A. Protective role of Aloe vera agains t X-ray induced tes ticular dysfunction. Andrologia. 2017; 49(7).
9. Behmanesh MA, Najafzadehvarzi H, Poormoosavi SM. Protective effect of Aloe vera extract agains t bisphenol a induced tes ticular toxicity in wis tar rats. Cell J. 2018; 20(2): 278-283.
10. Es takhr J, Javdan N. Spermatogenic activity of Aloe vera in adult male rats. Pharmacologyonline. 2011; 2: 886-889.
11. Es takhr J, Javdan N, Nikravesh A, Marzbani N. Spermatogenic activity of Aloe vera; increasing sperm parameters and CREM gene expression. Int J Fertil S teril. 2010; 4 Suppl 1: P-69.
12. Im K, Lee JY, Byeon H, Hwang KW, Kang W, Whang WK, et al. In Vitro antioxidative and anti-inflammatory activities of the ethanol extract of eggplant (Solanum melongena) s talks in macrophage RAW 264.7 cells. Food Agric Immunol. 2016; 27(6): 758-771.
13. Behmanesh MA, Efani Majd N, Shahriari A, Nnajafzadeh H. Evaluation of antioxidant potential of Aloe vera and pituitary sexual hormones after experimental diabetes in male rats. Iran J Vet Med. 2017; 11 (2): 164-174.
14. Lomeli N, Di K, Czerniawski J, Guzowski JF, Bota DA. Cisplatin-induced mitochondrial dysfunction is associated with impaired cognitive function in rats. Free Radic Biol Med. 2017; 102: 274-86.
15. Sahu BD, Kuncha M, Putcha UK, Sis tla R. Effect of metformin agains t cisplatin induced acute renal injury in rats: a biochemical and his toarchitectural evaluation. Exp Toxicol Pathol. 2013; 65(6): 933-940.
16. Ferrière S, Peyron I, Chris tophe OD, Kawecki C, Casari C, Muczynski V, et al. A hemophilia A mouse model for the in vivo assessment of emicizumab function. Blood. 2020; 136(6): 740-748.
17. Adebayo AO, Akinloye AK, Oke BO, Taiwo VO. Relationship between body mass index (BMI) and tes ticular and hormonal parameters of sexually active male greater cane rats (Thryonomys swinderianus). Anim Reprod. 2020; 17(1): e20190026.
18. Adibmoradi M, Morovvati H, Moradi HR, Sheybani MT, Amoli JS, Mazaheri Nezhad Fard R, et al. Protective effects of wheat sprout on tes ticular toxicity in male rats exposed to lead. Reprod Sys t Sex Disord. 2015; 4(4): 1-9.
19. Doctor Aras toye Marandi M, Yadegari M, Shahedi A, Pourentezari M, Anvari M, Shahrokhi Raeini A, et al. Effects of icariin on his tomorphometric changes of tes tis and pros tate induced by acrylamide in mice. Int J Med Lab. 2020; 7(3): 197-211.
20. Aksu EH, Kandemir FM, Özkaraca M, Ömür AD, Küçükler S, Çomaklı S. Rutin ameliorates cisplatin-induced reproductive damage via suppression of oxidative s tress and apoptosis in adult male rats. Andrologia. 2017; 49(1).
21. Türk G, Ateşşahin A, Sönmez M, Çeribaşi AO, Yüce A. Improvement of cisplatin-induced injuries to sperm quality, the oxidant-antioxidant sys tem, and the his tologic s tructure of the rat tes tis by ellagic acid. Fertil S teril. 2008; 89 5 Suppl: 1474-1481.
22. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72: 248-254.
23. Buege JA, Aus t SD. Microsomal lipid peroxidation. Methods Enzymol. 1978; 52: 302-310.
24. Kakkar P, Das B, Viswanathan PN. A modified spectrophotometric assay of superoxide dismutase. Indian J Biochem Biophys. 1984; 21(2): 130-132.
25. Amin A, Abraham C, Hamza AA, Abdalla ZA, Al-Shamsi SB, Harethi SS, et al. A s tandardized extract of Ginkgo biloba neutralizes cisplatin-mediated reproductive toxicity in rats. J Biomed Biotechnol. 2012; 2012: 362049.
26. Asadi N, Bahmani M, Kheradmand A, Rafieian-Kopaei M. The impact of oxidative s tress on tes ticular function and the role of antioxidants in improving it: a review. J Clin Diagn Res. 2017; 11(5): IE01-IE05.
27. Saral S, Ozcelik E, Cetin A, Saral O, Basak N, Aydın M, et al. Protective role of Diospyros lotus on cisplatin-induced changes in sperm characteris tics, tes ticular damage and oxidative s tress in rats. Andrologia. 2016; 48(3): 308-317.
28. Kaya K, Ciftci O, Cetin A, Doğan H, Başak N. Hesperidin protects tes ticular and spermatological damages induced by cisplatin in rats. Andrologia. 2015; 47(7): 793-800.
29. El-Amir YO, Yahia D, Yousef MS. Protective effect of avenanthramides agains t cisplatin induced tes ticular degeneration in rats. J Adv Vet Anim Res. 2019; 9(1): 14-22.
30. Silici S, Ekmekcioglu O, Eraslan G, Demirtas A. Antioxidative effect of royal jelly in cisplatin-induced tes tes damage. Urology. 2009; 74 (3): 545-551.
31. Tremellen K. Oxidative s tress and male infertility--a clinical perspective. Hum Reprod Update. 2008; 14 (3): 243-258.
32. Bonde JP, Giwercman A, Erns t E. Identifying environmental risk to male reproductive function by occupational sperm s tudies: logis tics and design options. Occup Environ Med. 1996; 53 (8): 511-519.
33. Imaga N, Osime E, Ezeji S, Okafor U. Effect of Aloe vera gel and selenium on cisplatin-induced oxidative s tress in Wis ter albino rats (LB155). FASEB J. 2014; 28 Suppl 1: LB155.
34. Chatterjee P, Mukherjee A, Nandy S. Protective effects of the aqueous leaf extract of Aloe barbadensis on gentamicin and cisplatin–induced nephrotoxic rats. Asian Pac J Trop Biomed. 2012; 2(3): S1754-1763.
35. Modaresi M, Khodaii H, Khodadadi A. The effects of Aloe vera extract on spermatogenesis and reproductive hormones in mice. J Anim Biol. 2013; 6(1): 69-76.
36. Mehranjani MS, Taefi R. The protective role of vitamin E on the tes ticular tissue in rats exposed to sodium arsenite during the prenatal s tage till sex maturity: a s tereological analysis. Iran J Reprod Med. 2012; 10(6): 571-580.
37. Sönmez M, Türk G, Yüce A. The effect of ascorbic acid supplementation on sperm quality, lipid peroxidation and tes tos terone levels of male Wis tar rats. Theriogenology. 2005; 63(7): 2063-2072.
38. Kammoun M, Miladi S, Ali YB, Damak M, Gargouri Y, Bezzine S. In vitro s tudy of the PLA2 inhibition and antioxidant activities of Aloe vera leaf skin extracts. Lipids Health Dis. 2011; 10(1): 30.