Gallik Asit Sıçanlarda Metotreksatın Neden Olduğu Oksidatif Yumurtalık Hasarını Azaltır
Yıl 2024,
Cilt: 3 Sayı: 4, 119 - 125
Selim Demir
,
Nihal Türkmen Alemdar
,
Elif Ayazoglu Demir
,
Ahmet Mentese
,
Yüksel Aliyazıcıoğlu
Öz
Metotreksat (MTX) kanser tedavisinde etkili bir kemoterapötik ajan olmasına rağmen, üreme sistemi de dahil olmak üzere sistemik doku toksisitesinin ortaya çıkması nedeniyle kullanımı sınırlanmaktadır. Gallik asit (GAL), son yıllarda oksidatif stres (OS) ile ilişkili çeşitli patolojik durumlara karşı faydalı etkiler gösterdiği kanıtlanmış bir fenolik bileşiktir. Bu çalışma, MTX'in neden olduğu yumurtalık hasarının tedavisinde GAL'ın terapötik potansiyelini ilk kez araştırmak için tasarlandı. Yetişkin dişi sıçanlar (n=30) rastgele beş gruba ayrıldı: kontrol, MTX, MTX+GAL (2,5 ve 5 mg/kg) ve yalnızca yüksek doz GAL (5 mg/kg). Yumurtalık toksisitesi tek doz intraperitoneal MTX (20 mg/kg) enjeksiyonu ile oluşturuldu. Tedavi gruplarına ise 2,5 ve 5 mg/kg dozundaki GAL ardışık üç gün boyunca intraperitoneal yoldan uygulandı. Çalışmanın beşinci gününde toplanan yumurtalık doku örneklerinde OS, inflamasyon ve apoptoz seviyeleri spektrofotometrik yöntemler kullanılarak belirlendi. Bulgular, GAL tedavisinin, MTX'e maruz bırakılan sıçanlarda yumurtalık lipid peroksidasyon, inflamasyon ve apoptoz seviyesini azalttığını ve yumurtalık antioksidan sistemini desteklediğini gösterdi. Bu çalışmanın sonuçları, GAL'ın MTX ile ilişkili oksidatif ve inflamatuar yumurtalık hasarını iyileştirme potansiyeline sahip olabileceğini göstermektedir. GAL'ın bu yumurtalık koruyucu etkisinin daha kapsamlı klinik öncesi çalışmalarla doğrulanması gerekmektedir.
Kaynakça
- Valerio V, Kwok M, Loewen H, et al. Systematic review of recommendations on the use of methotrexate in rheumatoid arthritis. Clin Rheumatol. 2021;40(4):1259-1271. doi:10.1007/s10067-020-05363-2
- Hamed KM, Dighriri IM, Baomar AF, et al. Overview of methotrexate toxicity: A comprehensive literature review. Cureus. 2022;14(9):e29518. doi:10.7759/cureus.29518
- Hortu I, Ozceltik G, Ergenoglu AM, Yigitturk G, Atasoy O, Erbas O. Protective effect of oxytocin on a methotrexate-induced ovarian toxicity model. Arch Gynecol Obstet. 2020;301(5):1317-1324. doi:10.1007/s00404-020-05534-1
- Fu J, Liu Y, Wang C, et al. Persistent follicular granulosa cell senescence and apoptosis induced by methotrexate leading to oocyte dysfunction and aberrant embryo development. Clin Transl Sci. 2021;14(5):2043-2054. doi:10.1111/cts.13068
- Benian A, Guralp O, Uzun DD, Okyar A, Sahmay S. The effect of repeated administration of methotrexate (MTX) on rat ovary: measurement of serum antimullerian hormone (AMH) levels. Gynecol Endocrinol. 2013;29(3):226-229. doi:10.3109/09513590.2012.738725
- Turkler C, Onat T, Yildirim E, et al. An experimental study on the use of lycopene to prevent infertility due to acute oxidative ovarian damage caused by a single high dose of methotrexate. Adv Clin Exp Med. 2020;29(1):5-11. doi:10.17219/acem/111809
- Karri S, Vanithakumari G. Effect of methotrexate and leucovorin on female reproductive tract of albino rats. Cell Biochem Funct. 2011;29(1):1-21. doi:10.1002/cbf.1711
- Gol M, Saygili U, Koyuncuoglu M, Uslu T. Influence of high-dose methotrexate therapy on the primordial follicles of the mouse ovary. J Obstet Gynaecol Res. 2009;35(3):429-433. doi:10.1111/j.1447-0756.2008.00945.x
- Ulug P, Oner G. Evaluation of the effects of single or multiple dose methotrexate administration, salpingectomy on ovarian reserve of rat with the measurement of anti-mullerian hormone (AMH) levels and histological analysis. Eur J Obstet Gynecol Reprod Biol. 2014;181:205-209. doi:10.1016/j.ejogrb.2014.07.011
- Kyaw MT, Sakthiswary R, Ani Amelia Z, Rahana AR, Munirah MM. Effects of methotrexate therapy on the levels of gonadotropic hormones in rheumatoid arthritis patients of reproductive age. Cureus. 2020;12(4):e7632. doi:10.7759/cureus.7632
- Murthy V, Chamberlain RS. Menopausal symptoms in young survivors of breast cancer: A growing problem without an ideal solution. Cancer Control. 2012;19(4):317-329. doi:10.1177/107327481201900408
- El-Sheikh AA, Morsy MA, Abdalla AM, Hamouda AH, Alhaider IA. Mechanisms of thymoquinone hepatorenal protection in methotrexate-induced toxicity in rats. Mediators Inflamm. 2015;2015:859383. doi:10.1155/2015/859383
- Yucel Y, Oguz E, Kocarslan S, et al. The effects of lycopene on methotrexate-induced liver injury in rats. Bratisl Lek Listy. 2017;118(4):212-216. doi:10.4149/BLL_2017_042
- Soylu Karapinar O, Pinar N, Özcan O, Özgür T, Dolapçıoğlu K. Protective effect of alpha-lipoic acid in methotrexate-induced ovarian oxidative injury and decreased ovarian reserve in rats. Gynecol Endocrinol. 2017;33(8):653-659. doi:10.1080/09513590.2017.1306847
- Gunyeli I, Saygin M, Ozmen O. Methotrexate-induced toxic effects and the ameliorating effects of astaxanthin on genitourinary tissues in a female rat model. Arch Gynecol Obstet. 2021;304(4):985-997. doi:10.1007/s00404-021-06000-2
- Eigenbrodt E, Glossmann H. Glycolysis-one of the keys to cancer? Trends Pharmacol Sci. 1980;89:359-362. doi:10.1016/0165-6147(80)90009-7
- Babiak RM, Campello AP, Carnieri EG, Oliveira MB. Methotrexate: pentose cycle and oxidative stress. Cell Biochem Funct. 1998;16(4):283-293. doi:10.1002/(SICI)1099-0844(1998120)16:4<283::AID-CBF801>3.0.CO;2-E
- Uraz S, Tahan V, Aygun C, et al. Role of ursodeoxycholic acid in prevention of methotrexate-induced liver toxicity. Dig Dis Sci. 2008;53(4):1071-1077. doi:10.1007/s10620-007-9949-3
- Jahovic N, Çevik H, Şehirli AÖ, Yeğen BÇ, Şener G. Melatonin prevents methotrexate‐induced hepatorenal oxidative injury in rats. J Pineal Res. 2003;34(4): 282-287. doi:10.1034/j.1600-079X.2003.00043.x
- Ayazoglu Demir E, Mentese A, Livaoglu A, Alemdar NT, Demir S. Ameliorative effect of gallic acid on cisplatin-induced ovarian toxicity in rats. Drug Chem Toxicol. 2023;46(1):97-103. doi:10.1080/01480545.2021.2011312
- Demir S, Kazaz IO, Kerimoglu G, et al. Gallic acid attenuates torsion/detorsion-induced testicular injury in rats through suppressing of HMGB1/NF-κB axis and endoplasmic reticulum stress. Rev Int Androl. 2024;22(1):1-7. doi:10.22514/j.androl.2024.001
- Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB. Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal. 2014;20(7):1126-1167. doi:10.1089/ars.2012.5149
- Gao J, Hu J, Hu D, Yang X. A role of gallic acid in oxidative damage diseases: A comprehensive review. Nat Prod Commun. 2019;14(8):1-9. doi:10.1177/1934578X19874174
- Bai J, Zhang Y, Tang C, et al. Gallic acid: Pharmacological activities and molecular mechanisms involved in inflammation-related diseases. Biomed Pharmacother. 2021;133:110985. doi:10.1016/j.biopha.2020.110985
- Ul-Haq Shah MZ, Soni M, Shrivastava VK, Mir MA, Muzamil S. Gallic acid reverses ovarian disturbances in mice with letrozole-induced PCOS via modulating Adipo R1 expression. Toxicol Rep. 2022;9:1938-1949. doi:10.1016/j.toxrep.2022.10.009
- Silva RLDS, Lins TLBG, Monte APOD, et al. Protective effect of gallic acid on doxorubicin-induced ovarian toxicity in mouse. Reprod Toxicol. 2023;115:147-156. doi:10.1016/j.reprotox.2022.12.008
- Ramkumar KM, Vijayakumar RS, Vanitha P, et al. Protective effect of gallic acid on alloxan-induced oxidative stress and osmotic fragility in rats. Hum Exp Toxicol. 2014;33(6):638-649. doi:10.1177/0960327113504792
- Smith PK, Krohn RI, Hermanson GT, et al. Measurement of protein using bicinchoninic acid. Anal Biochem. 1985;150(1):76-85. doi:10.1016/0003-2697(85)90442-7
- Mihara M, Uchiyama M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem. 1978;86(1):271-278. doi:10.1016/0003-2697(78)90342-1
- Demir S, Kazaz IO, Kerimoglu G, et al. Propolis ameliorates ischemia/reperfusion-induced testicular damage by reducing oxidative stress. Rev Int Androl. 2023;21(3):100364. doi:10.1016/j.androl.2023.100364
- Demir S, Mentese A, Livaoglu A, Demir EA, Alemdar NT, Aliyazicioglu Y. Therapeutic effect of sinapic acid against 5-fluorouracil-induced oxidative stress and inflammation in rat ovarium: An experimental approach. Farabi Med J. 2023;2(2):1-7. doi:10.59518/farabimedj.1221397
- Boots CE, Gustofson RL, Feinberg EC. Does methotrexate administration for ectopic pregnancy after in vitro fertilization impact ovarian reserve or ovarian responsiveness? Fertil Steril. 2013;100(6):1590-1593. doi:10.1016/j.fertnstert.2013.08.007
- Mahajan N. Fertility preservation in female cancer patients: An overview. J Hum Reprod Sci. 2015;8(1):3-13. doi:10.4103/0974-1208.153119
- Ayazoglu Demir E, Mentese A, Livaoglu A, Alemdar NT, Aliyazicioglu Y, Demir S. Chlorogenic acid attenuates cisplatin-induced ovarian injury in rats. Drug Chem Toxicol. 2024;47(2):213-217. doi:10.1080/01480545.2023.2172181
- Selimoğlu Şen H, Şen V, Bozkurt M, et al. Carvacrol and pomegranate extract in treating methotrexate-induced lung oxidative injury in rats. Med Sci Monit. 2014;20:1983-1990. doi:10.12659/MSM.890972
- Yuksel Y, Yuksel R, Yagmurca M, et al. Effects of quercetin on methotrexate-induced nephrotoxicity in rats. Hum Exp Toxicol. 2017;36(1):51-61. doi:10.1177/0960327116637414
- Vardi N, Parlakpinar H, Cetin A, Erdogan A, Cetin Ozturk I. Protective effect of beta-carotene on methotrexate-induced oxidative liver damage. Toxicol Pathol. 2010;38(4):592-597. doi:10.1177/0192623310367806
- Kulkarni JM, Swamy AHMV. Cardioprotective effect of gallic acid against doxorubicin‑induced myocardial toxicity in albino rats. Indian J Health Sci. 2015;8(1):28-35. doi:10.4103/2349-5006.158219
- Olayinka ET, Ore A, Ola OS, Adeyemo OA. Ameliorative effect of gallic acid on cyclophosphamide-induced oxidative injury and hepatic dysfunction in rats. Med Sci. 2015;3:78-92. doi:10.3390/medsci3030078
- Kilic K, Sakat MS, Akdemir FNE, Yildirim S, Saglam YS, Askin S. Protective effect of gallic acid against cisplatin-induced ototoxicity in rats. Braz J Otorhinolaryngol. 2019;85(3):267-274. doi:10.1016/j.bjorl.2018.03.001
- Abarikwu SO, Mgbudom-Okah CJ, Njoku RCC, Okonkwo CJ, Onuoha CC, Wokoma AFS. Gallic acid ameliorates busulfan-induced testicular toxicity and damage in mature rats. Drug Chem Toxicol. 2022;45(4):1881-1890. doi:10.1080/01480545.2021.1892949
- Phillips DC, Woollard KJ, Griffiths HR. The anti-inflammatory actions of methotrexate are critically dependent upon the production of reactive oxygen species. Br J Pharmacol. 2003;138(3):501-511. doi:10.1038/sj.bjp.0705054
- Althagafy HS, Sharawi ZW, Batawi AH, et al. Buspirone attenuated methotrexate-induced hippocampal toxicity in rats by regulating Nrf2/HO-1, PPAR-γ, NF-κB/nNOS, and ROS/NLRP3/caspase-1 signaling pathways. J Biochem Mol Toxicol. 2023;37(9):e23414. doi:10.1002/jbt.23414
- Famurewa AC, Folawiyo AM, Enohnyaket EB, et al. Beneficial role of virgin coconut oil supplementation against acute methotrexate chemotherapy-induced oxidative toxicity and inflammation in rats. Integr Med Res. 2018;7(3):257-263. doi:10.1016/j.imr.2018.05.001
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- Dehghani MA, Maram NS, Moghimipour E, Khorsandi L, Khah MA, Mahdavinia M. Protective effect of gallic acid and gallic acid-loaded Eudragit-RS 100 nanoparticles on cisplatin-induced mitochondrial dysfunction and inflammation in rat kidney. Biochim Biophys Acta Mol Basis Dis. 2020;1866(12):165911. doi:10.1016/j.bbadis.2020.165911
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Gallic Acid Alleviates Methotrexate‐Induced Oxidative Ovarian Damage in Rats
Yıl 2024,
Cilt: 3 Sayı: 4, 119 - 125
Selim Demir
,
Nihal Türkmen Alemdar
,
Elif Ayazoglu Demir
,
Ahmet Mentese
,
Yüksel Aliyazıcıoğlu
Öz
Although methotrexate (MTX) is an effective chemotherapeutic agent in the treatment of cancer, its use is limited due to the occurrence of systemic tissue toxicity, including those affecting the reproductive system. Gallic acid (GAL) is a phenolic compound that has been demonstrated to exert beneficial effects in a number of pathological conditions associated with oxidative stress (OS) in recent years. This study was designed to investigate the potential therapeutic benefits of GAL in the treatment of MTX-induced ovarian damage, for the first time. Adult female rats (n=30) were randomly allocated to five groups: control, MTX, MTX+GAL (2.5 and 5 mg/kg) and high-dose GAL only (5 mg/kg). A single intraperitoneal injection of MTX (20 mg/kg) was administered to induce ovarian toxicity. The treatment groups were administered 2.5 and 5 mg/kg of GAL intraperitoneally for a period of three consecutive days. The levels of OS, inflammation and apoptosis were determined in ovarian tissue samples collected on the fifth day of the study using spectrophotometric methods. The results showed that GAL treatment reduced the level of ovarian lipid peroxidation, inflammation, and apoptosis and promoted the ovarian antioxidant system in rats subjected to MTX. The results of this study indicate that GAL may have the potential to ameliorate MTX-associated oxidative and inflammatory ovarian damage. The ovarian protective effect of GAL requires further confirmation through more extensive preclinical studies.
Etik Beyan
This study was approved by the Local Animal Research Ethics Committee of Karadeniz Technical University (Protocol no: 2023/07) and performed according to the animal research reporting of in vivo experiments (ARRIVE) guidelines.
Teşekkür
The authors wish to thank Sait Al and Ibrahim Aydin from Surgical Practice and Research Center of Karadeniz Technical University for professional assistance with the experimental studies.
Kaynakça
- Valerio V, Kwok M, Loewen H, et al. Systematic review of recommendations on the use of methotrexate in rheumatoid arthritis. Clin Rheumatol. 2021;40(4):1259-1271. doi:10.1007/s10067-020-05363-2
- Hamed KM, Dighriri IM, Baomar AF, et al. Overview of methotrexate toxicity: A comprehensive literature review. Cureus. 2022;14(9):e29518. doi:10.7759/cureus.29518
- Hortu I, Ozceltik G, Ergenoglu AM, Yigitturk G, Atasoy O, Erbas O. Protective effect of oxytocin on a methotrexate-induced ovarian toxicity model. Arch Gynecol Obstet. 2020;301(5):1317-1324. doi:10.1007/s00404-020-05534-1
- Fu J, Liu Y, Wang C, et al. Persistent follicular granulosa cell senescence and apoptosis induced by methotrexate leading to oocyte dysfunction and aberrant embryo development. Clin Transl Sci. 2021;14(5):2043-2054. doi:10.1111/cts.13068
- Benian A, Guralp O, Uzun DD, Okyar A, Sahmay S. The effect of repeated administration of methotrexate (MTX) on rat ovary: measurement of serum antimullerian hormone (AMH) levels. Gynecol Endocrinol. 2013;29(3):226-229. doi:10.3109/09513590.2012.738725
- Turkler C, Onat T, Yildirim E, et al. An experimental study on the use of lycopene to prevent infertility due to acute oxidative ovarian damage caused by a single high dose of methotrexate. Adv Clin Exp Med. 2020;29(1):5-11. doi:10.17219/acem/111809
- Karri S, Vanithakumari G. Effect of methotrexate and leucovorin on female reproductive tract of albino rats. Cell Biochem Funct. 2011;29(1):1-21. doi:10.1002/cbf.1711
- Gol M, Saygili U, Koyuncuoglu M, Uslu T. Influence of high-dose methotrexate therapy on the primordial follicles of the mouse ovary. J Obstet Gynaecol Res. 2009;35(3):429-433. doi:10.1111/j.1447-0756.2008.00945.x
- Ulug P, Oner G. Evaluation of the effects of single or multiple dose methotrexate administration, salpingectomy on ovarian reserve of rat with the measurement of anti-mullerian hormone (AMH) levels and histological analysis. Eur J Obstet Gynecol Reprod Biol. 2014;181:205-209. doi:10.1016/j.ejogrb.2014.07.011
- Kyaw MT, Sakthiswary R, Ani Amelia Z, Rahana AR, Munirah MM. Effects of methotrexate therapy on the levels of gonadotropic hormones in rheumatoid arthritis patients of reproductive age. Cureus. 2020;12(4):e7632. doi:10.7759/cureus.7632
- Murthy V, Chamberlain RS. Menopausal symptoms in young survivors of breast cancer: A growing problem without an ideal solution. Cancer Control. 2012;19(4):317-329. doi:10.1177/107327481201900408
- El-Sheikh AA, Morsy MA, Abdalla AM, Hamouda AH, Alhaider IA. Mechanisms of thymoquinone hepatorenal protection in methotrexate-induced toxicity in rats. Mediators Inflamm. 2015;2015:859383. doi:10.1155/2015/859383
- Yucel Y, Oguz E, Kocarslan S, et al. The effects of lycopene on methotrexate-induced liver injury in rats. Bratisl Lek Listy. 2017;118(4):212-216. doi:10.4149/BLL_2017_042
- Soylu Karapinar O, Pinar N, Özcan O, Özgür T, Dolapçıoğlu K. Protective effect of alpha-lipoic acid in methotrexate-induced ovarian oxidative injury and decreased ovarian reserve in rats. Gynecol Endocrinol. 2017;33(8):653-659. doi:10.1080/09513590.2017.1306847
- Gunyeli I, Saygin M, Ozmen O. Methotrexate-induced toxic effects and the ameliorating effects of astaxanthin on genitourinary tissues in a female rat model. Arch Gynecol Obstet. 2021;304(4):985-997. doi:10.1007/s00404-021-06000-2
- Eigenbrodt E, Glossmann H. Glycolysis-one of the keys to cancer? Trends Pharmacol Sci. 1980;89:359-362. doi:10.1016/0165-6147(80)90009-7
- Babiak RM, Campello AP, Carnieri EG, Oliveira MB. Methotrexate: pentose cycle and oxidative stress. Cell Biochem Funct. 1998;16(4):283-293. doi:10.1002/(SICI)1099-0844(1998120)16:4<283::AID-CBF801>3.0.CO;2-E
- Uraz S, Tahan V, Aygun C, et al. Role of ursodeoxycholic acid in prevention of methotrexate-induced liver toxicity. Dig Dis Sci. 2008;53(4):1071-1077. doi:10.1007/s10620-007-9949-3
- Jahovic N, Çevik H, Şehirli AÖ, Yeğen BÇ, Şener G. Melatonin prevents methotrexate‐induced hepatorenal oxidative injury in rats. J Pineal Res. 2003;34(4): 282-287. doi:10.1034/j.1600-079X.2003.00043.x
- Ayazoglu Demir E, Mentese A, Livaoglu A, Alemdar NT, Demir S. Ameliorative effect of gallic acid on cisplatin-induced ovarian toxicity in rats. Drug Chem Toxicol. 2023;46(1):97-103. doi:10.1080/01480545.2021.2011312
- Demir S, Kazaz IO, Kerimoglu G, et al. Gallic acid attenuates torsion/detorsion-induced testicular injury in rats through suppressing of HMGB1/NF-κB axis and endoplasmic reticulum stress. Rev Int Androl. 2024;22(1):1-7. doi:10.22514/j.androl.2024.001
- Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB. Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal. 2014;20(7):1126-1167. doi:10.1089/ars.2012.5149
- Gao J, Hu J, Hu D, Yang X. A role of gallic acid in oxidative damage diseases: A comprehensive review. Nat Prod Commun. 2019;14(8):1-9. doi:10.1177/1934578X19874174
- Bai J, Zhang Y, Tang C, et al. Gallic acid: Pharmacological activities and molecular mechanisms involved in inflammation-related diseases. Biomed Pharmacother. 2021;133:110985. doi:10.1016/j.biopha.2020.110985
- Ul-Haq Shah MZ, Soni M, Shrivastava VK, Mir MA, Muzamil S. Gallic acid reverses ovarian disturbances in mice with letrozole-induced PCOS via modulating Adipo R1 expression. Toxicol Rep. 2022;9:1938-1949. doi:10.1016/j.toxrep.2022.10.009
- Silva RLDS, Lins TLBG, Monte APOD, et al. Protective effect of gallic acid on doxorubicin-induced ovarian toxicity in mouse. Reprod Toxicol. 2023;115:147-156. doi:10.1016/j.reprotox.2022.12.008
- Ramkumar KM, Vijayakumar RS, Vanitha P, et al. Protective effect of gallic acid on alloxan-induced oxidative stress and osmotic fragility in rats. Hum Exp Toxicol. 2014;33(6):638-649. doi:10.1177/0960327113504792
- Smith PK, Krohn RI, Hermanson GT, et al. Measurement of protein using bicinchoninic acid. Anal Biochem. 1985;150(1):76-85. doi:10.1016/0003-2697(85)90442-7
- Mihara M, Uchiyama M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem. 1978;86(1):271-278. doi:10.1016/0003-2697(78)90342-1
- Demir S, Kazaz IO, Kerimoglu G, et al. Propolis ameliorates ischemia/reperfusion-induced testicular damage by reducing oxidative stress. Rev Int Androl. 2023;21(3):100364. doi:10.1016/j.androl.2023.100364
- Demir S, Mentese A, Livaoglu A, Demir EA, Alemdar NT, Aliyazicioglu Y. Therapeutic effect of sinapic acid against 5-fluorouracil-induced oxidative stress and inflammation in rat ovarium: An experimental approach. Farabi Med J. 2023;2(2):1-7. doi:10.59518/farabimedj.1221397
- Boots CE, Gustofson RL, Feinberg EC. Does methotrexate administration for ectopic pregnancy after in vitro fertilization impact ovarian reserve or ovarian responsiveness? Fertil Steril. 2013;100(6):1590-1593. doi:10.1016/j.fertnstert.2013.08.007
- Mahajan N. Fertility preservation in female cancer patients: An overview. J Hum Reprod Sci. 2015;8(1):3-13. doi:10.4103/0974-1208.153119
- Ayazoglu Demir E, Mentese A, Livaoglu A, Alemdar NT, Aliyazicioglu Y, Demir S. Chlorogenic acid attenuates cisplatin-induced ovarian injury in rats. Drug Chem Toxicol. 2024;47(2):213-217. doi:10.1080/01480545.2023.2172181
- Selimoğlu Şen H, Şen V, Bozkurt M, et al. Carvacrol and pomegranate extract in treating methotrexate-induced lung oxidative injury in rats. Med Sci Monit. 2014;20:1983-1990. doi:10.12659/MSM.890972
- Yuksel Y, Yuksel R, Yagmurca M, et al. Effects of quercetin on methotrexate-induced nephrotoxicity in rats. Hum Exp Toxicol. 2017;36(1):51-61. doi:10.1177/0960327116637414
- Vardi N, Parlakpinar H, Cetin A, Erdogan A, Cetin Ozturk I. Protective effect of beta-carotene on methotrexate-induced oxidative liver damage. Toxicol Pathol. 2010;38(4):592-597. doi:10.1177/0192623310367806
- Kulkarni JM, Swamy AHMV. Cardioprotective effect of gallic acid against doxorubicin‑induced myocardial toxicity in albino rats. Indian J Health Sci. 2015;8(1):28-35. doi:10.4103/2349-5006.158219
- Olayinka ET, Ore A, Ola OS, Adeyemo OA. Ameliorative effect of gallic acid on cyclophosphamide-induced oxidative injury and hepatic dysfunction in rats. Med Sci. 2015;3:78-92. doi:10.3390/medsci3030078
- Kilic K, Sakat MS, Akdemir FNE, Yildirim S, Saglam YS, Askin S. Protective effect of gallic acid against cisplatin-induced ototoxicity in rats. Braz J Otorhinolaryngol. 2019;85(3):267-274. doi:10.1016/j.bjorl.2018.03.001
- Abarikwu SO, Mgbudom-Okah CJ, Njoku RCC, Okonkwo CJ, Onuoha CC, Wokoma AFS. Gallic acid ameliorates busulfan-induced testicular toxicity and damage in mature rats. Drug Chem Toxicol. 2022;45(4):1881-1890. doi:10.1080/01480545.2021.1892949
- Phillips DC, Woollard KJ, Griffiths HR. The anti-inflammatory actions of methotrexate are critically dependent upon the production of reactive oxygen species. Br J Pharmacol. 2003;138(3):501-511. doi:10.1038/sj.bjp.0705054
- Althagafy HS, Sharawi ZW, Batawi AH, et al. Buspirone attenuated methotrexate-induced hippocampal toxicity in rats by regulating Nrf2/HO-1, PPAR-γ, NF-κB/nNOS, and ROS/NLRP3/caspase-1 signaling pathways. J Biochem Mol Toxicol. 2023;37(9):e23414. doi:10.1002/jbt.23414
- Famurewa AC, Folawiyo AM, Enohnyaket EB, et al. Beneficial role of virgin coconut oil supplementation against acute methotrexate chemotherapy-induced oxidative toxicity and inflammation in rats. Integr Med Res. 2018;7(3):257-263. doi:10.1016/j.imr.2018.05.001
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