Research Article

Effects of rosmarinic acid and quercetin on methotrexate-induced liver and small intestine damage in rats

Volume: 49 Number: 3 September 30, 2024
TR EN

Effects of rosmarinic acid and quercetin on methotrexate-induced liver and small intestine damage in rats

Abstract

Purpose: Rosmarinic acid (RA) is a natural phenolic compound with antioxidant and anti-inflammatory effects. Quercetin (QCT) is a powerful antioxidant that prevents oxidative damage and cell death by clearing oxygen radicals. It also has anti-inflammatory effects. In this study, it was aimed to compare the effects of RA and QCT against liver and small bowel damage that may occur due to methotrexate (MTX) use. Materials and Methods: The study was conducted on a model of MTX-induced liver and small intestine damage in 40 Spraque Dawley male rats. RA and QCT were administered separately and in combination prophylactically (MTX+QCT group, MTX+RA group, MTX+QCT+RA group respectively). At the end of the study, liver and small intestine tissue were removed. Histopathological evaluations were performed using scoring. Malondialdehyde level, superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities were examined in the tissues. Results: In the liver tissue, pathological findings of all prophylaxis groups decreased considerably. When compared to the control group, MDA level increased significantly in the MTX, MTX+RA and MTX+RA+QCT groups The SOD and GPX activities of the MTX group decreased significantly when compared to the control group. It was found that GPX activity increased in the MTX+QCT group and SOD activity increased in the MTX+QCT+RA group when compared to the MTX group. In addition, SOD activity was significantly increased in the MTX+QCT+RA group when compared to the MTX+RA and MTX+QCT groups. In the small intestine tissue, pathological findings decreased significantly in the MTX+QCT group. Pathological findings decreased slightly in MTX+RA, MTX+QCT+RA groups. MDA levels were significantly higher in the MTX and MTX+RA+QCT groups when compared to the control group. The SOD and GPX activities of the MTX group decreased significantly compared to the control group. GPX activity decreased significantly in the MTX+QCT and MTX+RA groups when compared to the control group. SOD activity increased significantly in MTX+RA+QCT group when compared to MTX group, GPX activity increased significantly in MTX+RA+QCT group compared to MTX+QCT group. Conclusion: RA and QCT may be effective in preventing liver damage caused by MTX. It was concluded that QCT may be more effective than RA in preventing small bowel injury caused by MTX.

Keywords

Rosmarinic acid, quercetin, methotrexate, liver, small intestine tissue

Supporting Institution

This study received no financial support

Ethical Statement

Ethical approval was obtained for this study from Karadeniz Technical University Animal Experiments Local Ethics Committee with Protocol no: 2022/17.

Thanks

We presented this study as an oral presentation at the 1th International Congress of Histology and Embryology (NICHE 2022), 26-28 May 2022, Türkiye.

References

  1. El-Sheikh AA, Morsy MA, Al-Taher AY. Multi-drug resistance protein (Mrp) 3 may be involved in resveratrol protection against methotrexate-induced testicular damage. Life Sci. 2014;119:40-6.
  2. Wang Y, Zhao TT, Zhao HY & Wang H. Melatonin protects methotrexate-induced testicular injury in rats. Eur Rev Med Pharmacol Sci. 2018;22:7517-25.
  3. Karri S, Vanithakumari G. Effect of methotrexate and leucovorin on female reproductive tract of albino rats. Cell Biochem Funct. 2011;29:1–21.
  4. Gökçe A, Oktar S, Koc A & Yonden Z. Protective effects of thymoquinone against methotrexate-induced testicular injury. Hum Exp Toxicol. 2011;30:897-903.
  5. Widemann BC, Adamson PC. Understanding and managing methotrexate nephrotoxicity. Oncologist. 2006;11:694-703.
  6. Yuluğ E, Türedi S, Alver A, Türedi S, & Kahraman C. Effects of resveratrol on methotrexate-induced testicular damage in rats. ScientificWorldJournal. 2013;2013:489659.
  7. Armagan A, Uzar E, Uz E, Yilmaz HR, Kutluhan S, Koyuncuoglu HR et al. Caffeic acid phenethyl ester modulates methotrexate-induced oxidative stress in testes of rat. Hum Exp Toxicol. 2008;7:547-52.
  8. Uzar E, Koyuncuoglu HR, Uz E, Yilmaz HR, Kutluhan S, Kilbas S et al. The activities of antioxidant enzymes and the level of malondialdehyde in cerebellum of rats subjected to methotrexate: protective effect of caffeic acid phenethyl ester. Mol Cell Biochem. 2006;291:63–8.
  9. Ciftci O, Cetin A, Aydin M, Kaya K, Oguz, F. Fish oil, contained in eicosapentaenoic acid and docosahexaenoic acid, attenuates testicular and spermatological damage induced by cisplatin in rats. Andrologia. 2014;46:1161-8.
  10. Gamaro GD, Suyenaga E, Borsoi M, Lermen J, Pereira P, Ardenghi P. Effect of rosmarinic and caffeic acids on inflammatory and nociception process in rats. ISRN Pharmacol. 2011;2011:451682.
APA
Öztürk Okatan, D., Okatan, İ. E., Kutlu, A., Şahin, E., Sağlam, N., Alver, A., & Yenilmez, E. (2024). Effects of rosmarinic acid and quercetin on methotrexate-induced liver and small intestine damage in rats. Cukurova Medical Journal, 49(3), 547-560. https://doi.org/10.17826/cumj.1430648
AMA
1.Öztürk Okatan D, Okatan İE, Kutlu A, et al. Effects of rosmarinic acid and quercetin on methotrexate-induced liver and small intestine damage in rats. Cukurova Med J. 2024;49(3):547-560. doi:10.17826/cumj.1430648
Chicago
Öztürk Okatan, Derya, İlyas Ercan Okatan, Abdulkadir Kutlu, et al. 2024. “Effects of Rosmarinic Acid and Quercetin on Methotrexate-Induced Liver and Small Intestine Damage in Rats”. Cukurova Medical Journal 49 (3): 547-60. https://doi.org/10.17826/cumj.1430648.
EndNote
Öztürk Okatan D, Okatan İE, Kutlu A, Şahin E, Sağlam N, Alver A, Yenilmez E (September 1, 2024) Effects of rosmarinic acid and quercetin on methotrexate-induced liver and small intestine damage in rats. Cukurova Medical Journal 49 3 547–560.
IEEE
[1]D. Öztürk Okatan et al., “Effects of rosmarinic acid and quercetin on methotrexate-induced liver and small intestine damage in rats”, Cukurova Med J, vol. 49, no. 3, pp. 547–560, Sept. 2024, doi: 10.17826/cumj.1430648.
ISNAD
Öztürk Okatan, Derya - Okatan, İlyas Ercan - Kutlu, Abdulkadir - Şahin, Elif - Sağlam, Neslihan - Alver, Ahmet - Yenilmez, Engin. “Effects of Rosmarinic Acid and Quercetin on Methotrexate-Induced Liver and Small Intestine Damage in Rats”. Cukurova Medical Journal 49/3 (September 1, 2024): 547-560. https://doi.org/10.17826/cumj.1430648.
JAMA
1.Öztürk Okatan D, Okatan İE, Kutlu A, Şahin E, Sağlam N, Alver A, Yenilmez E. Effects of rosmarinic acid and quercetin on methotrexate-induced liver and small intestine damage in rats. Cukurova Med J. 2024;49:547–560.
MLA
Öztürk Okatan, Derya, et al. “Effects of Rosmarinic Acid and Quercetin on Methotrexate-Induced Liver and Small Intestine Damage in Rats”. Cukurova Medical Journal, vol. 49, no. 3, Sept. 2024, pp. 547-60, doi:10.17826/cumj.1430648.
Vancouver
1.Derya Öztürk Okatan, İlyas Ercan Okatan, Abdulkadir Kutlu, Elif Şahin, Neslihan Sağlam, Ahmet Alver, Engin Yenilmez. Effects of rosmarinic acid and quercetin on methotrexate-induced liver and small intestine damage in rats. Cukurova Med J. 2024 Sep. 1;49(3):547-60. doi:10.17826/cumj.1430648