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Bitter melon (Momordica charantia) fruit extract ameliorates methotrexate‐induced reproductive toxicity in male rats

Year 2021, Volume: 34 Issue: 3, 222 - 228, 27.10.2021
https://doi.org/10.5472/marumj.988941

Abstract

Objective: Methotrexate (MTX) is a drug commonly used for the treatment of malign neoplastic and inflammatory diseases. Antioxidant
and anti-inflammatory effects of bitter melon (BM) were reported. The aim of this study was to examine the effects of BM
fruit extract on MTX-induced testicular and epididymal damage.
Materials and Methods: Sprague Dawley male rats were divided into three groups (n=8) as control, MTX and MTX+BM. A single dose
of MTX (20 mg/kg) was injected intraperitoneally to the MTX and MTX+BM groups. BM fruit extract (600 mg/kg) was applied to the
MTX+BM group orally for 5 days. Testes were examined for general histopathology, proliferating and apoptotic cells. The epididymis
samples were used for the evaluation of sperm morphology. Oxidative and inflammatory markers were analysed biochemically.
Results: Increased abnormal spermatozoa, degenerated seminiferous tubules with increased apoptotic cells and decreased proliferative
cells were observed in the MTX group. TNF-α, IL-1β, 8-hydroxy-2-deoxyguanosine and caspase-3 levels increased, superoxide
dismutase and catalase levels decreased in both testis and epididymis samples. All these histological and biochemical parameters
were ameliorated in the MTX+BM group.
Conclusion: Methotrexate causes testis damage by decreasing spermatogenic cells and increasing apoptosis through oxidative stress
and inflammation. BM extract improves testis and epididymis damage with its possible anti-oxidant and anti-inflammatory effects.

References

  • Padmanabhan S, Tripathi D, Vikram A, Ramarao P, Jena GB. Methotrexate-induced cytotoxicity and genotoxicity in germ cells of mice: intervention of folic and folinic acid. Mutat Res 2009; 673(1):43-52. doi: 10.1016/j.mrgentox.2008.11.011
  • Romao VC, Lima A, Bernardes M, Canhao H, Fonseca JE. Three decades of low-dose methotrexate in rheumatoid arthritis: can we predict toxicity?. Immunol Res 2014; 60(2-3):289-310. doi: 10.1007/s12026-014-8564-6
  • Sonmez MF, Cilenk KT, Karabulut D, et al. Protective effects of propolis on methotrexate-induced testis injury in rat. Biomed Pharmacother 2016; 79:44-51. doi: 10.1016/j.biopha.2016.02.002.
  • Maremanda KP, Jena GJB. Methotrexate-induced germ cell toxicity and the important role of zinc and SOD1: Investigation of molecular mechanisms. Biochem Biophys Res Commun 2017; 483(1):596-601. doi: 10.1016/j.bbrc.2016.12.098.
  • Belhan S, Comakli S, Kucukler S, Gulyuz F, Yildirim S, Yener Z. Effect of chrysin on methotrexate‐induced testicular damage in rats. Andrologia 2019; 51(1): e13145. doi: 10.1111/and.13145
  • Owumi SE, Ochaoga SE, Odunola OA, Farombi EO . Protocatechuic acid inhibits testicular and epididymal toxicity associated with methotrexate in rats. Andrologia 2019; 51(9):e13350. doi: 10.1111/and.13350
  • Felemban SG, Aldubayan MA, Alhowail AH, Almami IS. Vitamin B17 Ameliorates Methotrexate-Induced Reproductive Toxicity, Oxidative Stress, and Testicular Injury in Male Rats. Oxid Med Cell Longev 2020; 2020:4372719. doi: 10.1155/2020/4372719
  • Sarihan K, Yardimoglu M, Eraldemir F, Yazir Y, Acar E. Protective effects of apocynin on damaged testes of rats exposed to methotrexate. Turk J Med Sci 2020; 50(5):1409-140. doi: 10.3906/sag-1909-52
  • Xiong S, Song D, Xiang Y, et al. Reactive oxygen species, not Ca(2+) , mediates methotrexate-induced autophagy and apoptosis in spermatocyte cell line. Basic and Clin Pharmacol Toxicol 2020; 126(2):144-52. doi: 10.1111/bcpt.13306
  • Aslankoc R, Ozmen O, Ellidag HY. Ameliorating effects of agomelatine on testicular and epididymal damage induced by methotrexate in rats. J Biochem Mol Toxicol 2020; 34(3):e22445. doi: 10.1002/jbt.22445
  • Sur S, Ray RB. Bitter Melon (Momordica Charantia), a Nutraceutical Approach for Cancer Prevention and Therapy. Cancers 2020; 12(8):2064. doi: 10.3390/cancers12082064
  • Gong J, Sun F, Li Y, et al. Momordica charantia polysaccharides could protect against cerebral ischemia/reperfusion injury through inhibiting oxidative stress mediated c-Jun N-terminal kinase 3 signaling pathway. Neuropharmacology 2015; 91:123-34. doi: 10.1016/j.neuropharm.2014.11.020
  • Aljohi A, Matou-Nasri S, Ahmed N. Antiglycation and Antioxidant Properties of Momordica charantia. PLOS One. 2016; 11(8):e0159985-e. doi: 10.1371/journal.pone.0159985
  • Chen F, Huang G, Yang Z, Hou Y. Antioxidant activity of Momordica charantia polysaccharide and its derivatives. Int J Biol Macromol 2019; 138:673-80. doi: 10.1016/j.ijbiomac.2019.07.129 . doi: 10.1016/j.ijbiomac.2019.07.129
  • Solomon U, Ashorobi R. Evaluation of anti-inflammatory and membrane stabilizing property of aqueous leaf extract of Momordica charantia in rats. Afr J Biomed Res. 2009; 9. doi: 10.4314/ajbr.v9i2.48892
  • Deng Z, Yuan C, Yang J, et al. Behavioral defects induced by chronic social defeat stress are protected by Momordica charantia polysaccharides via attenuation of JNK3/PI3K/AKT neuroinflammatory pathway. Ann Transl Med 2019; 7(1):6. doi: 10.21037/atm.2018.12.08
  • Soliman GA, Abdel-Rahman RF, Ogaly HA, et al. Momordica charantia Extract Protects against Diabetes-Related Spermatogenic Dysfunction in Male Rats: Molecular and Biochemical Study. Molecules 2020; 25(22). doi: 10.3390/molecules25225255
  • Kim SK, Jung J, Jung JH, et al. Hypoglycemic efficacy and safety of Momordica charantia (bitter melon) in patients with type 2 diabetes mellitus. Complement Ther Med. 2020; 52:102524. doi: 10.1016/j.ctim.2020
  • Piskin A, Altunkaynak BZ, Tumentemur G, Kaplan S, Yazici OB, Hokelek M. The beneficial effects of Momordica charantia (bitter gourd) on wound healing of rabbit skin. J Dermatolog Treat 2014; 25(4):350-7. doi: 10.3109/09546634.2012.713459
  • Singh R, Garcia-Gomez I, Gudehithlu KP, Singh AK. Bitter melon extract promotes granulation tissue growth and angiogenesis in the diabetic wound. Adv in Skin Wound Care 2017; 30(1):16-26. doi: 10.1097/01.ASW.0000504758.86737.76
  • Schreiber CA, Wan L, Sun Y, Lu L, Krey LC, Lee-Huang S. The antiviral agents, MAP30 and GAP31, are not toxic to human spermatozoa and may be useful in preventing the sexual transmission of human immunodeficiency virus type 1. Fertil Steril 1999; 72(4):686-90. doi: 10.1016/s0015-0282(99)00302-7
  • Pitchakarn P, Ogawa K, Suzuki S, et al. Momordica charantia leaf extract suppresses rat prostate cancer progression in vitro and in vivo. Cancer Sci 2010; 101(10):2234-40. doi: 10.1111/j.1349-7006.2010.01669
  • Claflin AJ, Vesely DL, Hudson JL, et al. Inhibition of growth and guanylate cyclase activity of an undifferentiated prostate adenocarcinoma by an extract of the balsam pear (Momordica charantia abbreviata). Proc Natl Acad Sci U S A 1978;75(2):989-93. doi: 10.1073/pnas.75.2.989
  • Sumanth M, Chowdary GN. Antimutagenic activity of aqueous extract of Momordica charantia. Int J Biotech Mol Biol 2010; 1(4):42-6. doi: 10.5897/IJBMBR.9000003
  • Kaur M, Deep G, Jain AK, et al. Bitter melon juice activates cellular energy sensor AMP-activated protein kinase causing apoptotic death of human pancreatic carcinoma cells. Carcinogenesis 2013; 34(7):1585-92. doi: 10.1093/carcin/bgt081
  • Fan X, He L, Meng Y, Li G, Li L, Meng Y. α‑MMC and MAP30, two ribosome‑inactivating proteins extracted from Momordica charantia, induce cell cycle arrest and apoptosis in A549 human lung carcinoma cells. Mol Med Rep 2015; 11(5):3553-8. doi: 10.3892/mmr.2015.3176.
  • Deng Y, Tang Q, Zhang Y, et al. Protective effect of Momordica charantia water extract against liver injury in restraint-stressed mice and the underlying mechanism. Food Nutr Res 2017; 61(1):1348864. doi: 10.1080/16546628.2017.1348864
  • Subramani B, Krishnamurthy B. Effects of Momordica Charantia (Bitter gourd) on Oxidative Stress and Pro-Inflammatory Marker in Metabolic Syndrome Using a High-Ffructose Diet Induced Rat Model. Biomed Pharmacol J 2019; 12(1):305-24. doi:10.13005/bpj/1642
  • Koroglu KM, Cevik O, Sener G, Ercan F. Apocynin alleviates cisplatin-induced testicular cytotoxicity by regulating oxidative stress and apoptosis in rats. Andrologia. 2019; 51(4):e13227. doi: 10.1111/and.13227
  • Johnsen SG. Testicular Biopsy Score Count – A Method for Registration of Spermatogenesis in Human Testes: Normal Values and Results in 335 Hypogonadal Males. Hormones 1970; 1(1):2-25. doi: 10.1159/000178170
  • Chen SJ, Allam JP, Duan YG, Haidl G. Influence of reactive oxygen species on human sperm functions and fertilizing capacity including therapeutical approaches. Arch Gynecol Obstet 2013; 288(1):191-9. doi: 10.1007/s00404-013-2801-4
Year 2021, Volume: 34 Issue: 3, 222 - 228, 27.10.2021
https://doi.org/10.5472/marumj.988941

Abstract

References

  • Padmanabhan S, Tripathi D, Vikram A, Ramarao P, Jena GB. Methotrexate-induced cytotoxicity and genotoxicity in germ cells of mice: intervention of folic and folinic acid. Mutat Res 2009; 673(1):43-52. doi: 10.1016/j.mrgentox.2008.11.011
  • Romao VC, Lima A, Bernardes M, Canhao H, Fonseca JE. Three decades of low-dose methotrexate in rheumatoid arthritis: can we predict toxicity?. Immunol Res 2014; 60(2-3):289-310. doi: 10.1007/s12026-014-8564-6
  • Sonmez MF, Cilenk KT, Karabulut D, et al. Protective effects of propolis on methotrexate-induced testis injury in rat. Biomed Pharmacother 2016; 79:44-51. doi: 10.1016/j.biopha.2016.02.002.
  • Maremanda KP, Jena GJB. Methotrexate-induced germ cell toxicity and the important role of zinc and SOD1: Investigation of molecular mechanisms. Biochem Biophys Res Commun 2017; 483(1):596-601. doi: 10.1016/j.bbrc.2016.12.098.
  • Belhan S, Comakli S, Kucukler S, Gulyuz F, Yildirim S, Yener Z. Effect of chrysin on methotrexate‐induced testicular damage in rats. Andrologia 2019; 51(1): e13145. doi: 10.1111/and.13145
  • Owumi SE, Ochaoga SE, Odunola OA, Farombi EO . Protocatechuic acid inhibits testicular and epididymal toxicity associated with methotrexate in rats. Andrologia 2019; 51(9):e13350. doi: 10.1111/and.13350
  • Felemban SG, Aldubayan MA, Alhowail AH, Almami IS. Vitamin B17 Ameliorates Methotrexate-Induced Reproductive Toxicity, Oxidative Stress, and Testicular Injury in Male Rats. Oxid Med Cell Longev 2020; 2020:4372719. doi: 10.1155/2020/4372719
  • Sarihan K, Yardimoglu M, Eraldemir F, Yazir Y, Acar E. Protective effects of apocynin on damaged testes of rats exposed to methotrexate. Turk J Med Sci 2020; 50(5):1409-140. doi: 10.3906/sag-1909-52
  • Xiong S, Song D, Xiang Y, et al. Reactive oxygen species, not Ca(2+) , mediates methotrexate-induced autophagy and apoptosis in spermatocyte cell line. Basic and Clin Pharmacol Toxicol 2020; 126(2):144-52. doi: 10.1111/bcpt.13306
  • Aslankoc R, Ozmen O, Ellidag HY. Ameliorating effects of agomelatine on testicular and epididymal damage induced by methotrexate in rats. J Biochem Mol Toxicol 2020; 34(3):e22445. doi: 10.1002/jbt.22445
  • Sur S, Ray RB. Bitter Melon (Momordica Charantia), a Nutraceutical Approach for Cancer Prevention and Therapy. Cancers 2020; 12(8):2064. doi: 10.3390/cancers12082064
  • Gong J, Sun F, Li Y, et al. Momordica charantia polysaccharides could protect against cerebral ischemia/reperfusion injury through inhibiting oxidative stress mediated c-Jun N-terminal kinase 3 signaling pathway. Neuropharmacology 2015; 91:123-34. doi: 10.1016/j.neuropharm.2014.11.020
  • Aljohi A, Matou-Nasri S, Ahmed N. Antiglycation and Antioxidant Properties of Momordica charantia. PLOS One. 2016; 11(8):e0159985-e. doi: 10.1371/journal.pone.0159985
  • Chen F, Huang G, Yang Z, Hou Y. Antioxidant activity of Momordica charantia polysaccharide and its derivatives. Int J Biol Macromol 2019; 138:673-80. doi: 10.1016/j.ijbiomac.2019.07.129 . doi: 10.1016/j.ijbiomac.2019.07.129
  • Solomon U, Ashorobi R. Evaluation of anti-inflammatory and membrane stabilizing property of aqueous leaf extract of Momordica charantia in rats. Afr J Biomed Res. 2009; 9. doi: 10.4314/ajbr.v9i2.48892
  • Deng Z, Yuan C, Yang J, et al. Behavioral defects induced by chronic social defeat stress are protected by Momordica charantia polysaccharides via attenuation of JNK3/PI3K/AKT neuroinflammatory pathway. Ann Transl Med 2019; 7(1):6. doi: 10.21037/atm.2018.12.08
  • Soliman GA, Abdel-Rahman RF, Ogaly HA, et al. Momordica charantia Extract Protects against Diabetes-Related Spermatogenic Dysfunction in Male Rats: Molecular and Biochemical Study. Molecules 2020; 25(22). doi: 10.3390/molecules25225255
  • Kim SK, Jung J, Jung JH, et al. Hypoglycemic efficacy and safety of Momordica charantia (bitter melon) in patients with type 2 diabetes mellitus. Complement Ther Med. 2020; 52:102524. doi: 10.1016/j.ctim.2020
  • Piskin A, Altunkaynak BZ, Tumentemur G, Kaplan S, Yazici OB, Hokelek M. The beneficial effects of Momordica charantia (bitter gourd) on wound healing of rabbit skin. J Dermatolog Treat 2014; 25(4):350-7. doi: 10.3109/09546634.2012.713459
  • Singh R, Garcia-Gomez I, Gudehithlu KP, Singh AK. Bitter melon extract promotes granulation tissue growth and angiogenesis in the diabetic wound. Adv in Skin Wound Care 2017; 30(1):16-26. doi: 10.1097/01.ASW.0000504758.86737.76
  • Schreiber CA, Wan L, Sun Y, Lu L, Krey LC, Lee-Huang S. The antiviral agents, MAP30 and GAP31, are not toxic to human spermatozoa and may be useful in preventing the sexual transmission of human immunodeficiency virus type 1. Fertil Steril 1999; 72(4):686-90. doi: 10.1016/s0015-0282(99)00302-7
  • Pitchakarn P, Ogawa K, Suzuki S, et al. Momordica charantia leaf extract suppresses rat prostate cancer progression in vitro and in vivo. Cancer Sci 2010; 101(10):2234-40. doi: 10.1111/j.1349-7006.2010.01669
  • Claflin AJ, Vesely DL, Hudson JL, et al. Inhibition of growth and guanylate cyclase activity of an undifferentiated prostate adenocarcinoma by an extract of the balsam pear (Momordica charantia abbreviata). Proc Natl Acad Sci U S A 1978;75(2):989-93. doi: 10.1073/pnas.75.2.989
  • Sumanth M, Chowdary GN. Antimutagenic activity of aqueous extract of Momordica charantia. Int J Biotech Mol Biol 2010; 1(4):42-6. doi: 10.5897/IJBMBR.9000003
  • Kaur M, Deep G, Jain AK, et al. Bitter melon juice activates cellular energy sensor AMP-activated protein kinase causing apoptotic death of human pancreatic carcinoma cells. Carcinogenesis 2013; 34(7):1585-92. doi: 10.1093/carcin/bgt081
  • Fan X, He L, Meng Y, Li G, Li L, Meng Y. α‑MMC and MAP30, two ribosome‑inactivating proteins extracted from Momordica charantia, induce cell cycle arrest and apoptosis in A549 human lung carcinoma cells. Mol Med Rep 2015; 11(5):3553-8. doi: 10.3892/mmr.2015.3176.
  • Deng Y, Tang Q, Zhang Y, et al. Protective effect of Momordica charantia water extract against liver injury in restraint-stressed mice and the underlying mechanism. Food Nutr Res 2017; 61(1):1348864. doi: 10.1080/16546628.2017.1348864
  • Subramani B, Krishnamurthy B. Effects of Momordica Charantia (Bitter gourd) on Oxidative Stress and Pro-Inflammatory Marker in Metabolic Syndrome Using a High-Ffructose Diet Induced Rat Model. Biomed Pharmacol J 2019; 12(1):305-24. doi:10.13005/bpj/1642
  • Koroglu KM, Cevik O, Sener G, Ercan F. Apocynin alleviates cisplatin-induced testicular cytotoxicity by regulating oxidative stress and apoptosis in rats. Andrologia. 2019; 51(4):e13227. doi: 10.1111/and.13227
  • Johnsen SG. Testicular Biopsy Score Count – A Method for Registration of Spermatogenesis in Human Testes: Normal Values and Results in 335 Hypogonadal Males. Hormones 1970; 1(1):2-25. doi: 10.1159/000178170
  • Chen SJ, Allam JP, Duan YG, Haidl G. Influence of reactive oxygen species on human sperm functions and fertilizing capacity including therapeutical approaches. Arch Gynecol Obstet 2013; 288(1):191-9. doi: 10.1007/s00404-013-2801-4
There are 31 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Original Articles
Authors

Fatma Kanpalta This is me 0000-0001-9832-6938

Dilek Ozbeylı This is me 0000-0002-0250-9535

Ali Sen This is me 0000-0002-2144-5741

Ozge Cevık This is me 0000-0002-9325-3757

Goksel Sener This is me 0000-0001-7444-6193

Feriha Ercan This is me 0000-0003-2339-5669

Publication Date October 27, 2021
Published in Issue Year 2021 Volume: 34 Issue: 3

Cite

APA Kanpalta, F., Ozbeylı, D., Sen, A., Cevık, O., et al. (2021). Bitter melon (Momordica charantia) fruit extract ameliorates methotrexate‐induced reproductive toxicity in male rats. Marmara Medical Journal, 34(3), 222-228. https://doi.org/10.5472/marumj.988941
AMA Kanpalta F, Ozbeylı D, Sen A, Cevık O, Sener G, Ercan F. Bitter melon (Momordica charantia) fruit extract ameliorates methotrexate‐induced reproductive toxicity in male rats. Marmara Med J. October 2021;34(3):222-228. doi:10.5472/marumj.988941
Chicago Kanpalta, Fatma, Dilek Ozbeylı, Ali Sen, Ozge Cevık, Goksel Sener, and Feriha Ercan. “Bitter Melon (Momordica Charantia) Fruit Extract Ameliorates methotrexate‐induced Reproductive Toxicity in Male Rats”. Marmara Medical Journal 34, no. 3 (October 2021): 222-28. https://doi.org/10.5472/marumj.988941.
EndNote Kanpalta F, Ozbeylı D, Sen A, Cevık O, Sener G, Ercan F (October 1, 2021) Bitter melon (Momordica charantia) fruit extract ameliorates methotrexate‐induced reproductive toxicity in male rats. Marmara Medical Journal 34 3 222–228.
IEEE F. Kanpalta, D. Ozbeylı, A. Sen, O. Cevık, G. Sener, and F. Ercan, “Bitter melon (Momordica charantia) fruit extract ameliorates methotrexate‐induced reproductive toxicity in male rats”, Marmara Med J, vol. 34, no. 3, pp. 222–228, 2021, doi: 10.5472/marumj.988941.
ISNAD Kanpalta, Fatma et al. “Bitter Melon (Momordica Charantia) Fruit Extract Ameliorates methotrexate‐induced Reproductive Toxicity in Male Rats”. Marmara Medical Journal 34/3 (October 2021), 222-228. https://doi.org/10.5472/marumj.988941.
JAMA Kanpalta F, Ozbeylı D, Sen A, Cevık O, Sener G, Ercan F. Bitter melon (Momordica charantia) fruit extract ameliorates methotrexate‐induced reproductive toxicity in male rats. Marmara Med J. 2021;34:222–228.
MLA Kanpalta, Fatma et al. “Bitter Melon (Momordica Charantia) Fruit Extract Ameliorates methotrexate‐induced Reproductive Toxicity in Male Rats”. Marmara Medical Journal, vol. 34, no. 3, 2021, pp. 222-8, doi:10.5472/marumj.988941.
Vancouver Kanpalta F, Ozbeylı D, Sen A, Cevık O, Sener G, Ercan F. Bitter melon (Momordica charantia) fruit extract ameliorates methotrexate‐induced reproductive toxicity in male rats. Marmara Med J. 2021;34(3):222-8.