RENOPROTECTIVE EFFECTS OF GINGER EXTRACT ON METHOTREXATE-INDUCED NEPHROTOXICITY IN RATS: MODULATION OF INFLAMMATORY AND INJURY BIOMARKERS KIM-1 AND LCN-2
Abstract
Methotrexate is a medication that is employed to treat a variety of cancers and inflammatory diseases; however, its clinical application is restricted by its significant toxicity. Antioxidant properties and a variety of applications against a variety of maladies are possessed by natural ginger extract. The investigation focused on the protective properties of ginger extract in the context of Methotrexate-induced kidney toxicity in rodents. (25) rats were divided into five groups. The negative control (G1) received distilled water, the positive control (G2) received 25 mg/kg bw of MTX, the third group (G3) received 200 mg/kg for body weight of ginger extract, the fourth group received MTX with ginger extract together at concentration (25 mg /kg + 200mg). In comparison, the fifth group received MTX with ginger extract together at concentration 25 mg/kg bw + 400mg. Methotrexate were administered high doses via intraperitoneally one dose on the third day. After finshing of the treatment period, lipid profiles, oxidant‑antioxidant, and kidney function and IL-6 level, lipocalin 2 (Lcn-2), Kidney Injury Molecule-1 (Kim-1),sod2 gene, and GPx1. G2exhibite significant decreasing in organ weights and antioxidant concentration, while increasing kidney IL-6, Kim-1, Lcn-2 gene expression and oxidative stress, while gene expression of Gpx1 and sod1 gene was low. G5 showed improved these markers compared to G2. Ginger extract demonstrated higher protective efficacy against MTX ‑induced kidney toxicity.
Keywords:
Zingiber officinale, methotrexate, Oxidative stress, Nephrotoxicity, Antioxidant
Downloads
Download data is not yet available.
References
1. Ali N, Rashid S, Nafees S, et al. Beneficial ef-fects of Chrysin against methotrexate-induced hepatotoxicity via attenuation of oxidative stress and apoptosis. Mol Cell Biochem 2014; 385(1–2): 215–223.
2. Kalantar M, Kalantari H, Goudarzi M, et al. Crocin ameliorates methotrexate-induced liver injury via inhi- bition of oxidative stress and inflammation in rats. Pharmacol Rep 2019; 71(4): 746–752.
3. Abo-Haded HM, Elkablawy MA, Al-Johani Z, et al. Hepatoprotective effect of sitagliptin against metho- trexate induced liver toxicity. PloS One 2017; 12(3): e0174295.
4. Abdel-Daim MM, Khalifa HA, Abushouk AI, et al. Diosmin attenuates methotrexate-induced hepatic, renal and cardiac Injury: a biochemical and histopatho- logical study in mice. Oxid Med Cell Longev 2017; 2017: 3281670.
5. Ali N, Rashid S, Nafees S, et al. Protective effect of Chlorogenic acid against meth-otrexate induced oxida- tive stress, inflamma-tion and apoptosis in rat liver: an experimen-tal approach. Chem Biol Interact 2017; 272: 80–91.
6. Dalaklioglu S, Genc GE, Aksoy NH, et al. Resveratrol ameliorates methotrexate-induced hepatotoxicity in rats via inhibition of lipid peroxidation. Hum Exp Tox- icol 2013; 32(6): 662–671.
7. Jahovic N, Cevik H, Sehirli AO, et al. Mela-tonin pre- vents methotrexate-induced hepa-torenal oxidative injury in rats. J Pineal Res 2003; 34(4): 282–287.
8. Kalantari H, Asadmasjedi N, Abyaz MR, et al. Protective effect of inulin on methotrexate-induced liver toxicity in mice. Biomed Phar-macother 2019; 110: 943–950.
9. Uraz S, Tahan V, Aygun C, et al. Role of ur-sodeoxy- cholic acid in prevention of meth-otrexate-induced liver toxicity. Dig Dis Sci 2008; 53(4): 1071–1077.
10. Cetinkaya A, Bulbuloglu E, Kurutas EB, et al. N-acetylcysteine ameliorates methotrexate-induced oxidative liver damage in rats. Med Sci Monit 2006; 12(8): 274–278.
11. Ahmadzadeh, A., Zamani, N., Hassanian-Moghaddam, H. et al. Acute versus chronic methotrexate poisoning; a cross-sectional study. BMC Pharmacol Toxicol 20, 39 (2019). https://doi.org/10.1186/s40360-019-0316-8
12. Roghani M, Kalantari H, Khodayar MJ, et al. Alleviation of Liver Dysfunction, Oxidative Stress and Inflammation Underlies the Protec-tive Effect of Ferulic Acid in Methotrexate-Induced Hepatotoxicity. Drug Des Devel Ther. 2020;14:1933-1941. Published 2020 May 20. doi:10.2147/DDDT.S23710713.
13. Al-Kuraishy HM, Abd Hasan RR, Al-Gareeb AIA, et al. Elucidation of the role of α-lipoic acid and vitamin C in methotrexate-induced hepatoxicity in mice. Eur Rev Med Pharmacol Sci. 2023;27(6):2277-2287. doi:10.26355/eurrev_202303_31761
14. Patel NN, Ghodasara DJ, Pandey S, et al. Subacute toxicopathological studies of meth-otrexate in Wistar rats. Vet World 2014; 7(7): 489–495.
15. Marri, Shiva Shankar; Sekar, Mohnish; Adya, Keshavmurthy A; Inamadar, Arun C; Jana-gond, Ajit B. Acute Methotrexate Toxicity Managed with Leucovorin and Pegylated Granulocyte Colony-stimulating Factor: A Report of Two Cases and Review of Litera-ture. Clinical Dermatology Review 8(2):p 149-153, Apr–Jun 2024. | DOI: 10.4103/cdr.cdr_35_22.
16. Li Y., V.H. Tran, C.C. Duke, B.D. Roufogalis, Preventive and protective properties of Zingiber officinale (Ginger) in diabetes melli-tus, diabetic complications, and asso- ciated lipid and other metabolic disorders: a brief review, Evid.-Based Complement. Altern. Med. 2012 (2012).
17. An K. , D. Zhao, Z. Wang, J. Wu, Y. Xu, G. Xiao, Comparison of different drying methods on Chinese ginger (Zingiber officinale Ros-coe): changes in volatiles, che- mical profile, antioxidant properties, and microstructure, Food Chem. 197 (2016) 1292–1300.
18. Guo J., H. Wu, L. Du, W. Zhang, J. Yang, Comparative antioxidant properties of some gingerols and shogaols, and the relationship of their contents with the anti- oxidant poten-cies of fresh and dried ginger (Zingiber officinale Roscoe), J. Agric. Sci. Technol. 16 (5) (2014) 1063–1072.
19. Hyun‐Ji Kim, Ji‐Ae Shin, Yeong‐Geun Lee, Bohwan Jin, Won Woo Lee, Yosub Lee, Su‐Jung Choi, Jung‐Min Han, Min‐Hye Ahn, Ji‐Hoon Kim, Dong‐Guk Park, Seong‐Doo Hong, Se‐Chan Kang, Sung‐Dae Cho, Zingiber officinale promotes autophagy and apoptosis in human oral cancer through the C/EBP homologous protein, Cancer Science, 10.1111/cas.16248, 115, 8, (2701-2717), (2024).
20. Mao Q-Q, Xu X-Y, Cao S-Y, Gan R-Y, Corke H, Beta T, Li H-B. Bioactive Compounds and Bioactivities of Ginger (Zingiber officinale Roscoe). Foods. 2019; 8(6):185. https://doi.org/10.3390/foods8060185
21. Hamed M.A., S.A. Ali, N. Saba El-Rigal, Therapeutic potential of ginger against renal injury induced by carbon tetrachloride in rats, Sci. World J. 2012 (2012).
22. Reddy Y.A., M. Chalamaiah, B. Ramesh, G. Balaji, P. Indira, Ameliorating activity of ginger (Zingiber officinale) extract against lead in-duced renal toxicity in male rats, J. Food Sci. Technol. 51 (5) (2014) 908–914.
23. Rong X., G. Peng, T. Suzuki, Q. Yang, J. Ya-mahara, Y. Li, A 35-day gavage safety assess-ment of ginger in rats, Regul. Toxicol. Phar-macol. 54 (2) (2009) 118–123.
24. Daher MH, Muraih JK. Influence of Capparis Spinosa Crude Extract on the Amylase Activ-ity in Vitro. Ann Rom Soc Cell Biol. 2021 Mar 1: 2410- 5.
25. 25- Redfern J, Kinninmonth M, Burdass D, Verran J. Using soxhlet ethanol extraction to produce and test plant material (essential oils) for their antimicrobial properties. J Microbiol Biol Educ. 2014 May; 15(1): 45-6.https://doi.org/10.1128/jmbe.v15i1.656.
26. SENER G., DEMIRALP E.E., CETINER M., et al.: L- carnitine ameliorates methotrexate-induced oxidative organ injury and inhibits leukocyte death. Cell. Biol. Toxicol., 22: 47-60, 2006.
27. WANG Z., HASEGAWA J., WANG X., et al.: Protective Effects of Ginger against Aspirin-Induced Gastric Ulcers in Rats. Yonago Acta. Medica., 54: 11-9, 2011.
28. Al Hroob AM, Abukhalil MH, Alghonmeen RD, Mahmoud AM. Ginger alleviates hyper-glycemia-induced oxidative stress, inflamma-tion and apoptosis and protects rats against diabetic nephropathy. Biomed Pharmacother. 2018 Oct;106:381-389. doi: 10.1016/j.biopha.2018.06.148. Epub 2018 Jul 11. PMID: 29966984.
29. Burow S, Fontaine R, von Krogh K, Mayer I, Nourizadeh-Lillabadi R, Hollander-Cohen L, et al. Follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh): Developmental pro-files of pituitary protein and gene expression levels. Gen Comp Endocrinol. 2019 Feb1; 272: 93-108.
30. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantita-tive PCR and the 2− ΔΔCT method. Methods. 2001 Dec 1; 25(4): 402-8.
31. Schefler, HG. Statistics for the biological sci-ences. Addison—Wesley Publishing Com-pany, London 1969. 232 S., 42 Tab., 12 Lit., Preis 65/—.https://doi.org/10.1002/bimj.19700120316 .
32. Sheron Latcha, Mohit Gupta, I-Hsin Lin, Edgar A. Jaimes (2023)” High Dose Methotrexate-Induced Acute Kidney Injury: Incidence, Risk Factors, and Recovery” Kidney International Reports,Volume 8, Issue 2, 360-364,ISSN 2468-0249, https://doi.org/10.1016/j.ekir.2022.10.029.
33. Welbat JU, Naewla S, Pannangrong W, Sirichoat A, Aranarochana A, Wigmore P. Neuroprotective effects of hesperidin against methotrexate-induced changes in neurogene-sis and oxidative stress in the adult rat. Bio-chem Pharmacol. 2020;178:114083. https://doi.org/10.1016/j.bcp.2020.114083.
34. Wang C, Leng M, Ding C, et al. Ferritino-phagy-mediated ferroptosis facilitates meth-otrexate-induced hepatotoxicity by high-mobility group box 1 (HMGB1). Liver Int. 2024;44(3):691-705. https://doi.org/10.1111/liv.15811.
35. Bergström, B., Selldén, T., Bollmann, M. et al. Methotrexate promotes the release of granu-locyte–macrophage colony-stimulating factor from rheumatoid arthritis fibroblast-like synoviocytes via autocrine interleukin-1 sig-naling. Arthritis Res Ther 26, 178 (2024). https://doi.org/10.1186/s13075-024-03406-6.
36. Wang, B., Deng, H., Hu, Y. et al. The differ-ence of lipid profiles between psoriasis with arthritis and psoriasis without arthritis and sex-specific downregulation of methotrexate on the apolipoprotein B/apolipoprotein A-1 ratio. Arthritis Res Ther 24, 17 (2022). https://doi.org/10.1186/s13075-021-02715-4.
37. Asghari-Jafarabadi M, Khalili L. The Effect of Ginger (Zingiber officinale) on Improving Blood Lipids and Body Weight; A Systematic Review and Multivariate Meta-analysis of Clinical Trials. Curr Pharm Des. 2022;28(35):2920-2943. https://doi.org/10.2174/1381612828666220926093847.
38. Shaukat, M.N.; Nazir, A.; Fallico, B. Ginger Bioactives: A Comprehensive Review of Health Benefits and Potential Food Applica-tions. Antioxidants 2023, 12, 2015. https://doi.org/10.3390/antiox12112015.
39. Hoseinzadeh Moghaddam S., Vatankhah A., Armide N., Keshavarzi Z. Revisiting the pro-tective effects of ginger phenolic compounds on the kidneys: A narrative review // Food and Humanity. 2024. Vol. 3. p. 100442.
40. Yang K, Lu Y, Yue Z, et al. 6-Gingerol acti-vates the Nrf2 signaling pathway to alleviate hydrogen peroxide induced oxidative stress on primary chicken embryo hepatocytes. Journal of Functional Foods. 2024;122:106535. https://doi.org/10.1016/j.jff.2024.106535.
41. Ayustaningwarno F, Anjani G, Ayu AM, Fogli-ano V. A critical review of Ginger's (Zingiber officinale) antioxidant, anti-inflammatory, and immunomodulatory activities. Front Nutr. 2024;11:1364836. Published 2024 Jun 6. https://doi.org/10.3389/fnut.2024.1364836.
42. Amin I, Hussain I, Rehman MU, et al. Zinger-one prevents lead-induced toxicity in liver and kidney tissues by regulating the oxidative damage in Wistar rats. J Food Biochem. 2021;45(3):e13241. https://doi.org/10.1111/jfbc.13241.
43. Fathi R, Akbari A, Nasiri K, Chardahcherik M. Ginger (Zingiber officinale roscoe) extract could upregulate the renal expression of NRF2 and TNFα and prevents ethanol-induced toxicity in rat kidney. Avicenna J Phytomed. 2021;11(2):134-145.
44. Veisi, P., Zarezade, M., Rostamkhani, H. et al. Renoprotective effects of the ginger (Zingiber officinale) on Diabetic kidney disease, current knowledge and future direction: a systematic review of animal studies. BMC Complement Med Ther 22, 291 (2022). https://doi.org/10.1186/s12906-022-03768-x.
45. Famurewa, A.C., Akhigbe, R.E., George, M.Y. et al. Mechanisms of ferroptotic and non-ferroptotic organ toxicity of chemotherapy: protective and therapeutic effects of ginger, 6-gingerol and zingerone in preclinical studies. Naunyn-Schmiedeberg's Arch Pharmacol 398, 4747–4778 (2025). https://doi.org/10.1007/s00210-024-03623-5.
2. Kalantar M, Kalantari H, Goudarzi M, et al. Crocin ameliorates methotrexate-induced liver injury via inhi- bition of oxidative stress and inflammation in rats. Pharmacol Rep 2019; 71(4): 746–752.
3. Abo-Haded HM, Elkablawy MA, Al-Johani Z, et al. Hepatoprotective effect of sitagliptin against metho- trexate induced liver toxicity. PloS One 2017; 12(3): e0174295.
4. Abdel-Daim MM, Khalifa HA, Abushouk AI, et al. Diosmin attenuates methotrexate-induced hepatic, renal and cardiac Injury: a biochemical and histopatho- logical study in mice. Oxid Med Cell Longev 2017; 2017: 3281670.
5. Ali N, Rashid S, Nafees S, et al. Protective effect of Chlorogenic acid against meth-otrexate induced oxida- tive stress, inflamma-tion and apoptosis in rat liver: an experimen-tal approach. Chem Biol Interact 2017; 272: 80–91.
6. Dalaklioglu S, Genc GE, Aksoy NH, et al. Resveratrol ameliorates methotrexate-induced hepatotoxicity in rats via inhibition of lipid peroxidation. Hum Exp Tox- icol 2013; 32(6): 662–671.
7. Jahovic N, Cevik H, Sehirli AO, et al. Mela-tonin pre- vents methotrexate-induced hepa-torenal oxidative injury in rats. J Pineal Res 2003; 34(4): 282–287.
8. Kalantari H, Asadmasjedi N, Abyaz MR, et al. Protective effect of inulin on methotrexate-induced liver toxicity in mice. Biomed Phar-macother 2019; 110: 943–950.
9. Uraz S, Tahan V, Aygun C, et al. Role of ur-sodeoxy- cholic acid in prevention of meth-otrexate-induced liver toxicity. Dig Dis Sci 2008; 53(4): 1071–1077.
10. Cetinkaya A, Bulbuloglu E, Kurutas EB, et al. N-acetylcysteine ameliorates methotrexate-induced oxidative liver damage in rats. Med Sci Monit 2006; 12(8): 274–278.
11. Ahmadzadeh, A., Zamani, N., Hassanian-Moghaddam, H. et al. Acute versus chronic methotrexate poisoning; a cross-sectional study. BMC Pharmacol Toxicol 20, 39 (2019). https://doi.org/10.1186/s40360-019-0316-8
12. Roghani M, Kalantari H, Khodayar MJ, et al. Alleviation of Liver Dysfunction, Oxidative Stress and Inflammation Underlies the Protec-tive Effect of Ferulic Acid in Methotrexate-Induced Hepatotoxicity. Drug Des Devel Ther. 2020;14:1933-1941. Published 2020 May 20. doi:10.2147/DDDT.S23710713.
13. Al-Kuraishy HM, Abd Hasan RR, Al-Gareeb AIA, et al. Elucidation of the role of α-lipoic acid and vitamin C in methotrexate-induced hepatoxicity in mice. Eur Rev Med Pharmacol Sci. 2023;27(6):2277-2287. doi:10.26355/eurrev_202303_31761
14. Patel NN, Ghodasara DJ, Pandey S, et al. Subacute toxicopathological studies of meth-otrexate in Wistar rats. Vet World 2014; 7(7): 489–495.
15. Marri, Shiva Shankar; Sekar, Mohnish; Adya, Keshavmurthy A; Inamadar, Arun C; Jana-gond, Ajit B. Acute Methotrexate Toxicity Managed with Leucovorin and Pegylated Granulocyte Colony-stimulating Factor: A Report of Two Cases and Review of Litera-ture. Clinical Dermatology Review 8(2):p 149-153, Apr–Jun 2024. | DOI: 10.4103/cdr.cdr_35_22.
16. Li Y., V.H. Tran, C.C. Duke, B.D. Roufogalis, Preventive and protective properties of Zingiber officinale (Ginger) in diabetes melli-tus, diabetic complications, and asso- ciated lipid and other metabolic disorders: a brief review, Evid.-Based Complement. Altern. Med. 2012 (2012).
17. An K. , D. Zhao, Z. Wang, J. Wu, Y. Xu, G. Xiao, Comparison of different drying methods on Chinese ginger (Zingiber officinale Ros-coe): changes in volatiles, che- mical profile, antioxidant properties, and microstructure, Food Chem. 197 (2016) 1292–1300.
18. Guo J., H. Wu, L. Du, W. Zhang, J. Yang, Comparative antioxidant properties of some gingerols and shogaols, and the relationship of their contents with the anti- oxidant poten-cies of fresh and dried ginger (Zingiber officinale Roscoe), J. Agric. Sci. Technol. 16 (5) (2014) 1063–1072.
19. Hyun‐Ji Kim, Ji‐Ae Shin, Yeong‐Geun Lee, Bohwan Jin, Won Woo Lee, Yosub Lee, Su‐Jung Choi, Jung‐Min Han, Min‐Hye Ahn, Ji‐Hoon Kim, Dong‐Guk Park, Seong‐Doo Hong, Se‐Chan Kang, Sung‐Dae Cho, Zingiber officinale promotes autophagy and apoptosis in human oral cancer through the C/EBP homologous protein, Cancer Science, 10.1111/cas.16248, 115, 8, (2701-2717), (2024).
20. Mao Q-Q, Xu X-Y, Cao S-Y, Gan R-Y, Corke H, Beta T, Li H-B. Bioactive Compounds and Bioactivities of Ginger (Zingiber officinale Roscoe). Foods. 2019; 8(6):185. https://doi.org/10.3390/foods8060185
21. Hamed M.A., S.A. Ali, N. Saba El-Rigal, Therapeutic potential of ginger against renal injury induced by carbon tetrachloride in rats, Sci. World J. 2012 (2012).
22. Reddy Y.A., M. Chalamaiah, B. Ramesh, G. Balaji, P. Indira, Ameliorating activity of ginger (Zingiber officinale) extract against lead in-duced renal toxicity in male rats, J. Food Sci. Technol. 51 (5) (2014) 908–914.
23. Rong X., G. Peng, T. Suzuki, Q. Yang, J. Ya-mahara, Y. Li, A 35-day gavage safety assess-ment of ginger in rats, Regul. Toxicol. Phar-macol. 54 (2) (2009) 118–123.
24. Daher MH, Muraih JK. Influence of Capparis Spinosa Crude Extract on the Amylase Activ-ity in Vitro. Ann Rom Soc Cell Biol. 2021 Mar 1: 2410- 5.
25. 25- Redfern J, Kinninmonth M, Burdass D, Verran J. Using soxhlet ethanol extraction to produce and test plant material (essential oils) for their antimicrobial properties. J Microbiol Biol Educ. 2014 May; 15(1): 45-6.https://doi.org/10.1128/jmbe.v15i1.656.
26. SENER G., DEMIRALP E.E., CETINER M., et al.: L- carnitine ameliorates methotrexate-induced oxidative organ injury and inhibits leukocyte death. Cell. Biol. Toxicol., 22: 47-60, 2006.
27. WANG Z., HASEGAWA J., WANG X., et al.: Protective Effects of Ginger against Aspirin-Induced Gastric Ulcers in Rats. Yonago Acta. Medica., 54: 11-9, 2011.
28. Al Hroob AM, Abukhalil MH, Alghonmeen RD, Mahmoud AM. Ginger alleviates hyper-glycemia-induced oxidative stress, inflamma-tion and apoptosis and protects rats against diabetic nephropathy. Biomed Pharmacother. 2018 Oct;106:381-389. doi: 10.1016/j.biopha.2018.06.148. Epub 2018 Jul 11. PMID: 29966984.
29. Burow S, Fontaine R, von Krogh K, Mayer I, Nourizadeh-Lillabadi R, Hollander-Cohen L, et al. Follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh): Developmental pro-files of pituitary protein and gene expression levels. Gen Comp Endocrinol. 2019 Feb1; 272: 93-108.
30. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantita-tive PCR and the 2− ΔΔCT method. Methods. 2001 Dec 1; 25(4): 402-8.
31. Schefler, HG. Statistics for the biological sci-ences. Addison—Wesley Publishing Com-pany, London 1969. 232 S., 42 Tab., 12 Lit., Preis 65/—.https://doi.org/10.1002/bimj.19700120316 .
32. Sheron Latcha, Mohit Gupta, I-Hsin Lin, Edgar A. Jaimes (2023)” High Dose Methotrexate-Induced Acute Kidney Injury: Incidence, Risk Factors, and Recovery” Kidney International Reports,Volume 8, Issue 2, 360-364,ISSN 2468-0249, https://doi.org/10.1016/j.ekir.2022.10.029.
33. Welbat JU, Naewla S, Pannangrong W, Sirichoat A, Aranarochana A, Wigmore P. Neuroprotective effects of hesperidin against methotrexate-induced changes in neurogene-sis and oxidative stress in the adult rat. Bio-chem Pharmacol. 2020;178:114083. https://doi.org/10.1016/j.bcp.2020.114083.
34. Wang C, Leng M, Ding C, et al. Ferritino-phagy-mediated ferroptosis facilitates meth-otrexate-induced hepatotoxicity by high-mobility group box 1 (HMGB1). Liver Int. 2024;44(3):691-705. https://doi.org/10.1111/liv.15811.
35. Bergström, B., Selldén, T., Bollmann, M. et al. Methotrexate promotes the release of granu-locyte–macrophage colony-stimulating factor from rheumatoid arthritis fibroblast-like synoviocytes via autocrine interleukin-1 sig-naling. Arthritis Res Ther 26, 178 (2024). https://doi.org/10.1186/s13075-024-03406-6.
36. Wang, B., Deng, H., Hu, Y. et al. The differ-ence of lipid profiles between psoriasis with arthritis and psoriasis without arthritis and sex-specific downregulation of methotrexate on the apolipoprotein B/apolipoprotein A-1 ratio. Arthritis Res Ther 24, 17 (2022). https://doi.org/10.1186/s13075-021-02715-4.
37. Asghari-Jafarabadi M, Khalili L. The Effect of Ginger (Zingiber officinale) on Improving Blood Lipids and Body Weight; A Systematic Review and Multivariate Meta-analysis of Clinical Trials. Curr Pharm Des. 2022;28(35):2920-2943. https://doi.org/10.2174/1381612828666220926093847.
38. Shaukat, M.N.; Nazir, A.; Fallico, B. Ginger Bioactives: A Comprehensive Review of Health Benefits and Potential Food Applica-tions. Antioxidants 2023, 12, 2015. https://doi.org/10.3390/antiox12112015.
39. Hoseinzadeh Moghaddam S., Vatankhah A., Armide N., Keshavarzi Z. Revisiting the pro-tective effects of ginger phenolic compounds on the kidneys: A narrative review // Food and Humanity. 2024. Vol. 3. p. 100442.
40. Yang K, Lu Y, Yue Z, et al. 6-Gingerol acti-vates the Nrf2 signaling pathway to alleviate hydrogen peroxide induced oxidative stress on primary chicken embryo hepatocytes. Journal of Functional Foods. 2024;122:106535. https://doi.org/10.1016/j.jff.2024.106535.
41. Ayustaningwarno F, Anjani G, Ayu AM, Fogli-ano V. A critical review of Ginger's (Zingiber officinale) antioxidant, anti-inflammatory, and immunomodulatory activities. Front Nutr. 2024;11:1364836. Published 2024 Jun 6. https://doi.org/10.3389/fnut.2024.1364836.
42. Amin I, Hussain I, Rehman MU, et al. Zinger-one prevents lead-induced toxicity in liver and kidney tissues by regulating the oxidative damage in Wistar rats. J Food Biochem. 2021;45(3):e13241. https://doi.org/10.1111/jfbc.13241.
43. Fathi R, Akbari A, Nasiri K, Chardahcherik M. Ginger (Zingiber officinale roscoe) extract could upregulate the renal expression of NRF2 and TNFα and prevents ethanol-induced toxicity in rat kidney. Avicenna J Phytomed. 2021;11(2):134-145.
44. Veisi, P., Zarezade, M., Rostamkhani, H. et al. Renoprotective effects of the ginger (Zingiber officinale) on Diabetic kidney disease, current knowledge and future direction: a systematic review of animal studies. BMC Complement Med Ther 22, 291 (2022). https://doi.org/10.1186/s12906-022-03768-x.
45. Famurewa, A.C., Akhigbe, R.E., George, M.Y. et al. Mechanisms of ferroptotic and non-ferroptotic organ toxicity of chemotherapy: protective and therapeutic effects of ginger, 6-gingerol and zingerone in preclinical studies. Naunyn-Schmiedeberg's Arch Pharmacol 398, 4747–4778 (2025). https://doi.org/10.1007/s00210-024-03623-5.
Published
20/06/2026
Statistics
56 Views | 31 Downloads
Citatons
How to Cite
Razzaq, F. K., and M. A. R. Yaseen. “RENOPROTECTIVE EFFECTS OF GINGER EXTRACT ON METHOTREXATE-INDUCED NEPHROTOXICITY IN RATS: MODULATION OF INFLAMMATORY AND INJURY BIOMARKERS KIM-1 AND LCN-2”. International Journal of Pharmacognosy and Chemistry, Vol. 7, no. 2, June 2026, pp. 1-8, doi:10.46796/ijpc.v7i2.907.
Issue
Section
Research Article
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Copyright © Author(s) retain the copyright of this article.
.