Effect of Boswellia serrata extract on Methotrexate induced testicular damage
Abstract
This study aimed to determine the effect of Boswellia serrata extract on Methotrexate– induced testicular damage by evaluating antioxidant system, reproductive organ weights, some spermatological parametres and serum Testesterone levels. For this purpose, 40 Sprague Dawley rats were divided into 4 groups. 1. Control Group (n=10): No treatment was given for 10 days. 2. B. serrata Group (n=10): B. serrata was given by gavage at a dose of 500 mg·kg-1 for 10 days. 3. Methotrexate Group (n=10): Methotrexate was given intraperitoneally as a single dose of 20 mg·kg-1. 4. Methotrexate + B. serrata Group (n=10): After methotrexate was given intraperitoneally as a single dose of 20 mg·kg-1, 500 mg·kg-1 B. serrata was given by gavage for 10 days. It was determined that B. serrata significantly increased serum Testosterone levels (P<0.001), testicular GSH levels (P<0.001), motility of sperm (P<0.001), concentration of sperm (P<0.001), absolute ventral prostate (P<0.001) and absolute seminal vesicles (P<0.05) organ weight in Methotrexate + B. serrata group. The decrease in testicular MDA levels (P>0.05) and the increase in GSH–Px enzyme activity of testes (P>0.05) and final body weight (P>0.05) were not significant in Methotrexate + B. serrata group compared to the Methotrexate group. In conclusion, the negative effects of Methotrexate on the male reproductive system can be reduced by administering B. serrata extract.
Downloads
References
Schilsky RL. Methotrexate: An effective agent for treating cancer and building careers. The polyglutamate era. Stem Cells. [Internet]. 1996; 1(4):244–247. doi: https://doi.org/k4pd
Ede AEV, Laan RF, Blom HJ, De Abreu RA, Van De Putte. Methotrexate in rheumatoid arthritis: an update with focus on mechanisms involved in toxicity. Seminars in Arthritis Rheumatism. [Internet]. 1998; 27(5):277–292. doi: https://doi.org/b644pk
Kishi T, Tanaka Y, Ueda K. Evidence for hypomethylation in two children with acute lymphoblastic leukemia and leukoencephalopathy. Cancer. [Internet]. 2000; 89 (4):925–931. doi: https://doi.org/d39chz
Gaies E, Jebabli N, Trabelsi S, Salouage I, Charfi R, Lakhal M, Klouz A. Methotrexate side effects: review article. J. Drug Metabol. Toxicol. [Internet]. 2012; 3(4):1–5.doi: https://doi.org/k4pf
Braun J. Optimal administration and dosage of methotrexate. Clinic. Experim. Rheumatol. 2010; 28(5):46–51.
Jahovic, N, Sener G, Cevik H, Ersoy Y, Arbak S, Yeğen BC. Amelioration of methotrexate–induced enteritis by melatonin in rats. Cell Biochem. Funct. [Internet]. 2004; 22(3):169–78. doi: https://doi.org/fc489q
Sener G, Eksioglu–Demiralp E, Cetiner M, Ercan F, Yeğen BÇ. Beta–glucan ameliorates methotrexate–induced oxidative organ injury via its antioxidant and immunomodulatory effects. Europ.J. Pharmacol. [Internet]. 2006; 542(1–3):170–178. doi: https://doi.org/d2zbgf
Serati–Nouri H, Azarmi YA, Movahedin M. Effect of growth hormone on testicular dysfunction induced by methotrexate in rats. Androl. [Internet]. 2009; 41:105–110. doi: https://doi.org/b9mg72
Güvenç M, Aksakal M. Ameliorating effect of kisspeptin‐10 on methotrexate‐induced sperm damages and testicular oxidative stress in rats. Androl. [Internet]. 2018; 50(8):e13057. doi: https://doi.org/gfbr6s
Padmanabhan S, Tripathi DN, Vikram A, Ramarao P, Jena GB. Cytotoxic and genotoxic effects of methotrexate in germ cells of male Swiss mice. Mutation Res./Genet. Toxicol. Environm. Mutagen. [Internet]. 2008; 655(1–2):59–67. doi: https://doi.org/ftt3c2
Johnson FE, Farr SA, Mawad M, Woo YCS. Testicular cytotoxicity of intravenous methotrexate in rats. J. Surgic. Oncol. [Internet]. 1994; 55:175–178. doi: https://doi.org/bqhvdh
Saxena AK, Dhungel S, Bhattacharya S, Jha CB, Srivastava AK. Effect of chronic low dose of methotrexate on cellular proliferation during spermatogenesis in rats. Arch. Androl. [Internet]. 2004; 50:33–35. doi: https://doi.org/fbkbqm
Palo AK, Choudhury RC. Modulation of methotrexateinduced cytogenotoxicity in mouse spermatogonia and its transmission in the male germline by caffeine. Environm. Toxicol. Pharmacol. [Internet]. 2006; 21:254–259. doi: https://doi.org/dv68bj
Öktem F, Yilmaz HR, Ozguner F, Olgar S, Ayata A, Uzar E, Uz E. Methotrexate–induced renal oxidative stress in rats: the role of a novel antioxidant caffeic acid phenethyl ester. Toxicol. Industr. Health. [Internet]. 2006; 22:241–247. doi: https://doi.org/cvzsdj
Belhan S, Özkaraca M, Kandemir FM, Gülyüz F, Yıldırım S, Ömür AD, Yener Z. Effectiveness of hesperidin on methotrexate–induced testicular toxicity in rats. Kafkas Üniversitesi Veteriner Fakültesi Dergisi. [Internet]. 2017; 23(5):789–796. doi: 10.9775/kvfd.2017.17752
Al–Yasiry ARM, Kiczorowska B. Frankincense–therapeutic properties. Postępy Higieny i Medycyny Doświadczalnej. [Internet]. 2016; 70:380–391. doi: https://doi.org/k4pg
Hussain H, Al–Harrasi A, Csuk R, Shamraiz U, Green IR, Ahmed I, Khan IA, Ali Z. Therapeutic potential of boswellic acids: a patent review (1990–2015). Expert Opinion on Therap. Patents. [Internet]. 2017; 27(1):81–90. doi: https://doi.org/k4ph
Sharma A, Upadhyay J, Jain A, Kharya MD, Namdeo A, Mahadik KR. Antioxidant activity of aqueous extract of Boswellia serrata. J. Chem. Bio. Phy. Sci. 2011; 1(1):60–71.
Singh P, Chacko KM, Aggarwal ML, Bhat B, Khandal RK, Sultana S, Kuruvilla BT. A–90 Day Gavage Safety Assessment of Boswellia serrata in rats. Toxicol. Intern. [Internet]. 2012; 19(3):273–278. doi: https://doi.org/k4pk
Arkali G, Aksakal M, Kaya ŞÖ. Protective effects of carvacrol against diabetes–induced reproductive damage in male rats: Modulation of Nrf2/HO–1 signalling pathway and inhibition of Nf–kB–mediated testicular apoptosis and inflammation. Androl. [Internet]. 2021; 53:e13899. doi: https://doi.org/k4pn
Lowry OH. Protein measurement with folin phenol reagent. J. Biol. Chem. 1951; 193:265–275.
Placer ZA, Cushman LL, Johnson BC. Estamination of product of lipid peroxidation (Malonlydialdehyde) in biochemical systems. Analyt. Biochem. [Internet]. 1966; 16:359–64. doi: https://doi.org/b96rpj
Sedlak J, Lindsay RH. Estimation of total protein bound and nonprotein sulfhydryl groups in tissue with Ellmann’s reagent. Analyt. Biochem. [Internet]. 1968; 25:192–205. doi: https://doi.org/csbsfm
Lawrence RA, Burk RF. Glutathione peroxidase activity in selenium–deficient rat liver. Biochem. Biophys. Res. Commun. [Internet]. 1976; 71:952–958. doi: https://doi.org/d3vv59
Türk G, Ateşşahin A, Sönmez M, Yüce A, Çeribaşı AO. Lycopene protects against cyclosporine A–induced testicular toxicity in rats. Theriogenol. [Internet]. 2007; 67:778–785. doi: https://doi.org/fxghnh
Sönmez M, Türk G, Yüce A. The effect of ascorbic acid supplementation on sperm quality, lipid peroxidation and testosterone levels of male Wistar rats. Theriogenol. [Internet]. 2005; 63(7):2063–2072. doi: https://doi.org/cn6kn5
Armagan A, Uzar E, Uz E, Yilmaz HR, Kutluhan S, Koyuncuoglu HR, Soyupek S, Cam H, Serel TA. Caffeic acid phenethyl ester modulates methotrexate–induced oxidative stress in testes of rat. Human Experim. Toxicol. [Internet]. 2008; 27 (7):547–552. doi: https://doi.org/c4drd3
Aldhahrani A, Soliman MM, Althobaiti F, Alkhedaide A, Nassan MA, Mohamed WA, Youssef GBA, Said AM. The modulatory impacts of Glycyrrhiza glabra extract against methotrexate–induced testicular dysfunction and oxidative stress. Toxicol. Res. [Internet]. 2021; 10 (4): 677–686. doi: https://doi.org/k4pr
Belhan S, Çomaklı S, Küçükler S, Gülyüz F, Yıldırım S, Yener Z. Effect of chrysin on methotrexate‐induced testicular damage in rats. Androl. [Internet]. 2019; 51:e13145. doi: https://doi.org/gmcjq8
Mansour DF, Saleh DO, Ahmed–Farid OA, Rady M, Bakeer RM, Hashad IM. Ginkgo biloba extract (EGb 761) mitigates methotrexate–induced testicular insult in rats: Targeting oxidative stress, energy deficit and spermatogenesis. Biomed Pharmacother. [Internet]. 2021; 143:112201. doi: https://doi.org/k4ps
Al–Yahy AA, Asad M, Sadaby A, Alhussaini MS. Repeat oral dose safety study of standardized methanolic extract of Boswellia sacra oleo gum resin in rats. Saudi J. Biol. Sci. [Internet]. 2020; 27:117–123. doi: https://doi.org/k4pt
Sami MM, Ali EA, Galhom RA, Youssef AM, Mohammad HM. Boswellic acids ameliorate doxorubicin–induced nephrotoxicity in mice: A focus on antioxidant and antiapoptotic effects. Egyptian J. Basic Appl. Sci. [Internet]. 2019; 6:10–24. doi: https://doi.org/dhvvg8
Nusier MK, Bataineh HN, Bataineh ZM, Daradka HM. Effect of frankincense (Boswellia thurifera) on reproductive system in adult male rat. J. Health Sci. [Internet]. 2007; 53:365–370. doi: https://doi.org/k4pv
Padmanabhan S, Tripathi DN, Vikram A, Ramarao P, Jena GB. Methotrexateinduced cytotoxicity and genotoxicity in germ cells of mice: Intervention of folic and folinic acid. Mutation Res./Genet. Toxicol. Environm. Mutagenesis. [Internet]. 2009; 673:43–52. doi: https://doi.org/c23bc7
Armagan A, Uzar E, Uz E, Yilmaz HR, Kutluhan S, Koyuncuoglu HR, Soyupek S, Cam H, Serel TA. Caffeic acid phenethyl ester modulates methotrexate–induced oxidative stress in testes of rat. Human Experim. Toxicol. [Internet]. 2008; 27(7):547–552. doi: https://doi.org/c4drd3
Vardi N, Parlakpinar H, Ates B, Cetin A, Otlu A. Antiapoptotic and antioxidant effects of beta–carotene against methotrexate–induced testicular injury. Fertil. Steril. [Internet]. 2009; 92(6):2028–2033. doi: https://doi.org/b2n98v
Eid NAS, Shibata MA, Ito Y, Kusakabe K, Hammad H, Otsukı Y. Involvement of Fas system and active caspases in apoptotic signalling in testicular germ cells of ethanol–treated rats. Intern. J. Androl. [Internet]. 2002; 25(3):159–167. doi: https://doi.org/fq69t5
Sherif IO, Al–Mutabagan LA, Sarhan OM. Ginkgo biloba extract attenuates methotrexate–induced testicular ınjury in rats: Cross–talk between oxidative stress, inflammation, apoptosis, and miRNA–29a expression. Integrative Cancer Therap. [Internet]. 2020; 19:e–1534735420969814. doi: https://doi.org/k4pz
Yuluğ E, Türedi S, Alver A, Türedi S, Kahraman C. Effects of resveratrol on methotrexate–ınduced testicular damage in rats. The Scientif. World J. [Internet]. 2013; 2013:489659. doi: https://doi.org/gb7xk7
Doaee P, Rajaei Z, Roghani M, Alaei H, Kamalinejad M. Effects of Boswellia serrata resin extract on motor dysfunction and brain oxidative stress in an experimental model of Parkinson´s disease. Avicenna J. PhytoMed. 2019; 9(3):281–290.
Tohamy HG, El–kazaz SE, Alotaibi SS, İbrahiem HS, Shukry M, Mahmoud Dawood AO. Ameliorative effects of boswellic acid on fipronil–ınduced toxicity: Antioxidant state, apoptotic markers, and testicular steroidogenic expression in male rats. Anim. [Internet]. 2021; 11(5):1302. doi: https://doi.org/k4p5
Gupta M, Singh S, Kurmi A, Luqman S, Saikia D, Thomas M, Rout PK. Correlation of boswellic acids with antiproliferative, antioxidant and antimicrobial activities of topographically collected Boswellia serrata oleo–gum–resin. PhytoMed. [Internet]. 2022; 2:100289. doi: https://doi.org/k4p7
Yüncü M, Bükücü N, Bayat N, Sencar L, Tarakçıoğlu M. The effect of vitamin E and L–carnitine against methotrexate–induced injury in rat testis. Turkish J. Med. Sci. [Internet]. 2015; 45:517–525. doi: https://doi.org/k4p8
Aslankoc R, Ozmen O, Ellidag HY. Ameliorating effects of agomelatine on testicular andepididymal damage induced by methotrexate in rats J Biochem. Molec. Toxicol. [Internet]. 2020; 34:e22445. doi: https://doi.org/k4qb
Copyright (c) 2024 Gözde Arkalı, Tutku Can Acısu, Nida Badıllı, Edanur Güler–Ekmen, Osman Sedat Tanyeri, Abdullah Toz, Mehmet Çay, Abdurrauf Yüce, Mesut Aksakal
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.