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Oksaliplatin ve Naringin’in Dalak Dokusu Üzerine Etkilerinin Rat Modelinde Değerlendirilmesi

Year 2022, Volume: 2 Issue: 2, 72 - 80, 28.09.2022

Abstract

Oksaliplatin (OPL), kolorektal kanser tedavisinde yaygın olarak kullanılan platin bazlı kemoterapötik ajandır. Naringin (NRG) ise çeşitli biyolojik ve farmakolojik özelliklere sahip olan antioksidan bir bileşiktir. Sunulan çalışmada OPL ve NRG uygulamalarının ratların dalak dokusu üzerine etkileri değerlendirilmiştir. Ratlara çalışmanın 1. ve 2. günleri ile 5. ve 6. günlerinde oral olarak 50 veya 100 mg/kg vücut ağırlığı NRG verildikten 30 dakika sonra 4 mg/kg vücut ağırlığı OPL periton içine enjekte edildi. Daha sonra dalak dokusunda malondialdehit (MDA) ve glutatyon (GSH) seviyeleri ile nükleer faktöreritroid faktör 2-ilişkili faktör 2 (Nrf2), hem oksijenaz-1 (HO-1), nükleer faktör kappa B (NF-B), tümör nekroz faktörü alfa (TNF-), B hücreli lenfoma 2-ilişkili X proteini (Bax) ve Kaspaz-3 mRNA transkript seviyeleri analiz edilmiştir. Elde edilen veriler OPL tedavisi sonrası artan MDA seviyelerini NRG’nin azalttığını göstermiştir. Ayrıca OPL uygulaması ile azalan GSH, Nrf2 ve HO-1 seviyelerinin NRG tedavisi sonrası artış gösterdiği belirlendi. Ayrıca OPL ile tetiklenen NF-B, TNF-, Bax ve Kaspaz-3 ekspresyonlarının NRG tarafından aşağı yönlü düzenlendiği tespit edilmiştir. Sonuç olarak, OPL’nin dalak dokusunda oksidatif stres, enflamasyon ve apoptozu tetiklediği buna karşın NRG’nin OPL ile tetiklenen bu olayları tersine çevirdiği sonucuna varılmıştır.

References

  • 1. Adam R., Haller DG., Poston G., Raoul JL., Spano JP., Tabernero J., Van Cutsem E., 2010. Toward optimized front-line therapeutic strategies in patients with metastatic colorectal cancer an expert review from the International Congress on Anti-Cancer Treatment (ICACT) 2009. Annals of Oncology, 21, 1579-1584.
  • 2. Alam MA., Subhan N., Rahman MM., Uddin SJ., Reza HM., Sarker, SD., 2014. Effect of citrus flavonoids, naringin and naringenin, on metabolic syndrome and their mechanisms of action. Advances in Nutrition, 5, 404-417.
  • 3. Areti A., Komirishetty P., Kalvala AK., Nellaiappan K., Kumar, A., 2018. Rosmarinic Acid Mitigates Mitochondrial Dysfunction and Spinal Glial Activation in Oxaliplatin-induced Peripheral Neuropathy. Molecular Neurobiology, 55, 7463– 7475.
  • 4. Caglayan C., Temel Y., Kandemir FM., Yildirim S., Kucukler S., 2018. Naringin protects against cyclophosphamide-induced hepatotoxicity and nephrotoxicity through modulation of oxidative stress, inflammation, apoptosis, autophagy, and DNA damage. Environmental Science and Pollution Research, 25, 20968-20984.
  • 5. Celik H., Kucukler S., Ozdemir S., Comakli S., Gur C., Kandemir FM., Yardim A., 2020. Lycopene protects against central and peripheral neuropathy by inhibiting oxaliplatin-induced ATF-6 pathway, apoptosis, inflammation and oxidative stress in brains and sciatic tissues of rats. Neurotoxicology, 80, 29-40.
  • 6. de Gramont A., Figer A., Seymour M., Homerin M., Hmissi A., Cassidy J., Boni C., Cortes-Funes H., Cervantes A., Freyer G., Papamichael D., le Bail N., Louvet C., Hendler D., de Braud F., Wilson C., Morvan F., Bonetti A., 2000. Leucovorin and fluorouracil with or without oxaliplatin as firstline treatment in advanced colorectal cancer. Journal of Clinical Oncology, 18, 2938–2947.
  • 7. di Cesare Mannelli L., Zanardelli M., Failli P., Ghelardini C., 2013. Oxaliplatin-induced oxidative stress in nervous system-derived cellular models: Could it correlate with in vivo neuropathy? Free Radical Biology and Medicine, 61, 143–150.
  • 8. El Chediak A., Haydar A.A., Hakim A., Abdel Massih S., Hilal L., Mukherji D., Temraz S., Shamseddine A., 2018. Increase in spleen volume as a predictor of oxaliplatin toxicity. Therapeutics and Clinical Risk Management, 14, 653.
  • 9. Graham MA., Lockwood GF., Greenslade D., Brienza S., Bayssas M., Gamelin, E., 2000. Clinical pharmacokinetics of oxaliplatin: a critical review. Clinical Cancer Research, 6, 1205-1218.
  • 10. Gur C., Kandemir O., Kandemir FM., 2022a. Investigation of the effects of hesperidin administration on abamectin‐induced testicular toxicity in rats through oxidative stress, endoplasmic reticulum stress, inflammation, apoptosis, autophagy, and JAK2/STAT3 pathways. Environmental Toxicology, 37, 401- 412.
  • 11. Gur C., Kandemir FM., Darendelioglu E., Caglayan C., Kucukler S., Kandemir O., Ileriturk M., 2021. Morin protects against acrylamideinduced neurotoxicity in rats: an investigation into different signal pathways. Environmental Science and Pollution Research, 28, 49808- 49819.
  • 12. Gür C., Genç A., Kandemir Ö., 2022. Ratlarda Deltametrin’in Neden Olduğu Dalak Toksisitesine Karşı Rutin’in Potansiyel Koruyucun Etkilerinin Oksidatif Stres, Apoptoz ve İnflamasyon Belirteçleri Üzerinden Araştırılması. Atatürk Üniversitesi Veteriner Bilimleri Dergisi, 17, 6-10.
  • 13. Gür C., Kandemir Ö., Kandemir FM., 2022. Ratlarda diklofenak ile indüklenen kardiyotoksisite üzerine krisinin etkilerinin oksidatif stres, endoplazmik retikulum stresi ve apoptoz belirteçleri ile değerlendirilmesi. Kocatepe Veterinary Journal, 15, 151–160.
  • 14. Ileriturk M., Benzer F., Aksu EH., Yildirim S., Kandemir FM., Dogan T., Dortbudak MB., Genc A., 2021. Chrysin protects against testicular toxicity caused by lead acetate in rats with its antioxidant, anti‐inflammatory, and antiapoptotic properties. Journal of Food Biochemistry, 45, p.e13593.
  • 15. Kucukler S., Benzer F., Yildirim S., Gur C., Kandemir FM., Bengu AS., Ayna A., Caglayan C., Dortbudak, MB., 2021. Protective effects of chrysin against oxidative stress and inflammation induced by lead acetate in rat kidneys: a biochemical and histopathological approach. Biological Trace Element Research, 199, 1501-1514.
  • 16. Lees JG., White D., Keating BA., Barkl-Luke ME., Makker PG., Goldstein D., Moalem-Taylor G., 2020. Oxaliplatin-induced haematological toxicity and splenomegaly in mice. Plos one, 15, p.e0238164.
  • 17. Livak KJ., Schmittgen TD., 2001. Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method. Methods, 25, 402–408.
  • 18. Lu Y., Wu S., Xiang B., Li L., Lin Y., 2020. Curcumin Attenuates Oxaliplatin-Induced Liver Injury and Oxidative Stress by Activating the Nrf2 Pathway. Drug Design, Development and Therapy, 14, 73. 19. Kandemir FM., Ileriturk M., Gur C., 2022. Rutin protects rat liver and kidney from sodium valproate-induce damage by attenuating oxidative stress, ER stress, inflammation, apoptosis and autophagy. Molecular Biology Reports, 1-12.
  • 20. Kandemir FM., Kucukler S., Caglayan C., Gur C., Batil AA., Gülçin İ., 2017. Therapeutic effects of silymarin and naringin on methotrexate‐induced nephrotoxicity in rats: Biochemical evaluation of anti‐inflammatory, antiapoptotic, and antiautophagic properties. Journal of food biochemistry, 41, p.e12398.
  • 21. Placer ZA., Cushman LL., Johnson BC., 1966. Estimation of product of lipid peroxidation (malonyl dialdehyde) in biochemical systems. Analytical biochemistry, 16, 359-364.
  • 22. Recalde MD., Miguel CA., Noya-Riobó MV., Gonzalez SL., Villar MJ., Coronel MF., 2020. Resveratrol exerts anti-oxidant and antiinflammatory actions and prevents oxaliplatininduced mechanical and thermal allodynia. Brain Research, 1748, p.147079.
  • 23. Schwingel TE., Klein CP., Nicoletti NF., Dora CL., Hadrich G., Bica CG., Lopes TG., da Silva VD., Morrone FB., 2014. Effects of the compounds resveratrol, rutin, quercetin, and quercetin nanoemulsion on oxaliplatin-induced hepatotoxicity and neurotoxicity in mice. Naunyn-Schmiedeberg’s Archives of Pharmacology, 387, 837–848.
  • 24. Sedlak J., Lindsay RH., 1968. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Analytical biochemistry, 25, 192-205.
  • 25. Semis HS., Gur C., Ileriturk M., Kandemir FM., Kaynar O., 2022. Evaluation of Therapeutic Effects of Quercetin Against Achilles Tendinopathy in Rats via Oxidative Stress, Inflammation, Apoptosis, Autophagy, and Metalloproteinases. American Journal of Sports Medicine, 50, 486–498.
  • 26. Tabassum H., Waseem M., Parvez S., Qureshi MI., 2015. Oxaliplatin-induced Oxidative Stress Provokes Toxicity in Isolated Rat Liver Mitochondria. Archives of Medical Research, 46, 597–603.
  • 27. Wang YS., Li YY., Cui W., Li LB., Zhang ZC., Tian BP., Zhang GS., 2017. Melatonin attenuates pain hypersensitivity and decreases astrocytemediated spinal neuroinflammation in a rat model of oxaliplatin-induced pain. Inflammation, 40, 2052-2061.
  • 28. Xia T., Zhang J., Han L., Jin Z., Wang J., Li X., Man S., Liu C., Gao W., 2019. Protective effect of magnolol on oxaliplatin‐induced intestinal injury in mice. Phytotherapy Research, 33, 1161-1172.
  • 29. Yehia R., Saleh S., El Abhar H., Saad AS., Schaalan, M., 2019. L-Carnosine protects against Oxaliplatin-induced peripheral neuropathy in colorectal cancer patients: A perspective on targeting Nrf-2 and NF-κB pathways. Toxicology and applied pharmacology, 365, 41-50.
  • 30. Yesildag K., Gur C., Ileriturk M., Kandemir FM., 2022. Evaluation of oxidative stress, inflammation, apoptosis, oxidative DNA damage and metalloproteinases in the lungs of rats treated with cadmium and carvacrol. Molecular Biology Reports, 49, 1201–1211.
  • 31. Yıldız MO., Çelik H., Caglayan C., Kandemir FM., Gür C., Bayav İ., Genç A., Kandemir, Ö., 2022. Neuromodulatory effects of hesperidin against sodium fluoride-induced neurotoxicity in rats: Involvement of neuroinflammation, endoplasmic reticulum stress, apoptosis and autophagy. NeuroToxicology, 90, 197-204.

Evaluation of The Effects of Oxaliplatin and Naringin on Spleen Tissue in a Rat Model

Year 2022, Volume: 2 Issue: 2, 72 - 80, 28.09.2022

Abstract

Oxaliplatin (OPL) is a platinum-based chemotherapeutic agent widely used in the treatment of colorectal cancer. Naringin (NRG) is an antioxidant compound with various biological and pharmacological properties. In the present study, the effects of OPL and NRG administrations on spleen tissue of rats were evaluated. On the 1st and 2nd days of the study and on the 5th and 6th days of the study, 30 minutes after oral administration of 50 or 100 mg/kg body weight NRG, 4 mg/kg body weight OPL was injected intraperitoneally. Then, malondialdehyde (MDA) and glutathione (GSH) levels and nuclear factorerythroid factor 2-related factor-2 (Nrf2), heme oxygenase-1 (HO-1), nuclear factor kappa-B (NF-B), tumor necrosis factoralpha (TNF-), B-cell lymphoma 2-associated X protein (Bax), and Caspase-3 mRNA transcript levels were analyzed in spleen tissue. The data obtained showed that NRG reduced the increased MDA levels after OPL treatment. It was also determined that GSH, Nrf2 and HO-1 levels, which decreased with OPL administration, increased after NRG treatment. Moreover, OPLinduced NF-B, TNF-, Bax and Caspase-3 expressions were downregulated by NRG. Taken together, it was concluded that OPL triggered oxidative stress, inflammation and apoptosis in spleen tissue whereas NRG reversed these OPL-induced events.

References

  • 1. Adam R., Haller DG., Poston G., Raoul JL., Spano JP., Tabernero J., Van Cutsem E., 2010. Toward optimized front-line therapeutic strategies in patients with metastatic colorectal cancer an expert review from the International Congress on Anti-Cancer Treatment (ICACT) 2009. Annals of Oncology, 21, 1579-1584.
  • 2. Alam MA., Subhan N., Rahman MM., Uddin SJ., Reza HM., Sarker, SD., 2014. Effect of citrus flavonoids, naringin and naringenin, on metabolic syndrome and their mechanisms of action. Advances in Nutrition, 5, 404-417.
  • 3. Areti A., Komirishetty P., Kalvala AK., Nellaiappan K., Kumar, A., 2018. Rosmarinic Acid Mitigates Mitochondrial Dysfunction and Spinal Glial Activation in Oxaliplatin-induced Peripheral Neuropathy. Molecular Neurobiology, 55, 7463– 7475.
  • 4. Caglayan C., Temel Y., Kandemir FM., Yildirim S., Kucukler S., 2018. Naringin protects against cyclophosphamide-induced hepatotoxicity and nephrotoxicity through modulation of oxidative stress, inflammation, apoptosis, autophagy, and DNA damage. Environmental Science and Pollution Research, 25, 20968-20984.
  • 5. Celik H., Kucukler S., Ozdemir S., Comakli S., Gur C., Kandemir FM., Yardim A., 2020. Lycopene protects against central and peripheral neuropathy by inhibiting oxaliplatin-induced ATF-6 pathway, apoptosis, inflammation and oxidative stress in brains and sciatic tissues of rats. Neurotoxicology, 80, 29-40.
  • 6. de Gramont A., Figer A., Seymour M., Homerin M., Hmissi A., Cassidy J., Boni C., Cortes-Funes H., Cervantes A., Freyer G., Papamichael D., le Bail N., Louvet C., Hendler D., de Braud F., Wilson C., Morvan F., Bonetti A., 2000. Leucovorin and fluorouracil with or without oxaliplatin as firstline treatment in advanced colorectal cancer. Journal of Clinical Oncology, 18, 2938–2947.
  • 7. di Cesare Mannelli L., Zanardelli M., Failli P., Ghelardini C., 2013. Oxaliplatin-induced oxidative stress in nervous system-derived cellular models: Could it correlate with in vivo neuropathy? Free Radical Biology and Medicine, 61, 143–150.
  • 8. El Chediak A., Haydar A.A., Hakim A., Abdel Massih S., Hilal L., Mukherji D., Temraz S., Shamseddine A., 2018. Increase in spleen volume as a predictor of oxaliplatin toxicity. Therapeutics and Clinical Risk Management, 14, 653.
  • 9. Graham MA., Lockwood GF., Greenslade D., Brienza S., Bayssas M., Gamelin, E., 2000. Clinical pharmacokinetics of oxaliplatin: a critical review. Clinical Cancer Research, 6, 1205-1218.
  • 10. Gur C., Kandemir O., Kandemir FM., 2022a. Investigation of the effects of hesperidin administration on abamectin‐induced testicular toxicity in rats through oxidative stress, endoplasmic reticulum stress, inflammation, apoptosis, autophagy, and JAK2/STAT3 pathways. Environmental Toxicology, 37, 401- 412.
  • 11. Gur C., Kandemir FM., Darendelioglu E., Caglayan C., Kucukler S., Kandemir O., Ileriturk M., 2021. Morin protects against acrylamideinduced neurotoxicity in rats: an investigation into different signal pathways. Environmental Science and Pollution Research, 28, 49808- 49819.
  • 12. Gür C., Genç A., Kandemir Ö., 2022. Ratlarda Deltametrin’in Neden Olduğu Dalak Toksisitesine Karşı Rutin’in Potansiyel Koruyucun Etkilerinin Oksidatif Stres, Apoptoz ve İnflamasyon Belirteçleri Üzerinden Araştırılması. Atatürk Üniversitesi Veteriner Bilimleri Dergisi, 17, 6-10.
  • 13. Gür C., Kandemir Ö., Kandemir FM., 2022. Ratlarda diklofenak ile indüklenen kardiyotoksisite üzerine krisinin etkilerinin oksidatif stres, endoplazmik retikulum stresi ve apoptoz belirteçleri ile değerlendirilmesi. Kocatepe Veterinary Journal, 15, 151–160.
  • 14. Ileriturk M., Benzer F., Aksu EH., Yildirim S., Kandemir FM., Dogan T., Dortbudak MB., Genc A., 2021. Chrysin protects against testicular toxicity caused by lead acetate in rats with its antioxidant, anti‐inflammatory, and antiapoptotic properties. Journal of Food Biochemistry, 45, p.e13593.
  • 15. Kucukler S., Benzer F., Yildirim S., Gur C., Kandemir FM., Bengu AS., Ayna A., Caglayan C., Dortbudak, MB., 2021. Protective effects of chrysin against oxidative stress and inflammation induced by lead acetate in rat kidneys: a biochemical and histopathological approach. Biological Trace Element Research, 199, 1501-1514.
  • 16. Lees JG., White D., Keating BA., Barkl-Luke ME., Makker PG., Goldstein D., Moalem-Taylor G., 2020. Oxaliplatin-induced haematological toxicity and splenomegaly in mice. Plos one, 15, p.e0238164.
  • 17. Livak KJ., Schmittgen TD., 2001. Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method. Methods, 25, 402–408.
  • 18. Lu Y., Wu S., Xiang B., Li L., Lin Y., 2020. Curcumin Attenuates Oxaliplatin-Induced Liver Injury and Oxidative Stress by Activating the Nrf2 Pathway. Drug Design, Development and Therapy, 14, 73. 19. Kandemir FM., Ileriturk M., Gur C., 2022. Rutin protects rat liver and kidney from sodium valproate-induce damage by attenuating oxidative stress, ER stress, inflammation, apoptosis and autophagy. Molecular Biology Reports, 1-12.
  • 20. Kandemir FM., Kucukler S., Caglayan C., Gur C., Batil AA., Gülçin İ., 2017. Therapeutic effects of silymarin and naringin on methotrexate‐induced nephrotoxicity in rats: Biochemical evaluation of anti‐inflammatory, antiapoptotic, and antiautophagic properties. Journal of food biochemistry, 41, p.e12398.
  • 21. Placer ZA., Cushman LL., Johnson BC., 1966. Estimation of product of lipid peroxidation (malonyl dialdehyde) in biochemical systems. Analytical biochemistry, 16, 359-364.
  • 22. Recalde MD., Miguel CA., Noya-Riobó MV., Gonzalez SL., Villar MJ., Coronel MF., 2020. Resveratrol exerts anti-oxidant and antiinflammatory actions and prevents oxaliplatininduced mechanical and thermal allodynia. Brain Research, 1748, p.147079.
  • 23. Schwingel TE., Klein CP., Nicoletti NF., Dora CL., Hadrich G., Bica CG., Lopes TG., da Silva VD., Morrone FB., 2014. Effects of the compounds resveratrol, rutin, quercetin, and quercetin nanoemulsion on oxaliplatin-induced hepatotoxicity and neurotoxicity in mice. Naunyn-Schmiedeberg’s Archives of Pharmacology, 387, 837–848.
  • 24. Sedlak J., Lindsay RH., 1968. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Analytical biochemistry, 25, 192-205.
  • 25. Semis HS., Gur C., Ileriturk M., Kandemir FM., Kaynar O., 2022. Evaluation of Therapeutic Effects of Quercetin Against Achilles Tendinopathy in Rats via Oxidative Stress, Inflammation, Apoptosis, Autophagy, and Metalloproteinases. American Journal of Sports Medicine, 50, 486–498.
  • 26. Tabassum H., Waseem M., Parvez S., Qureshi MI., 2015. Oxaliplatin-induced Oxidative Stress Provokes Toxicity in Isolated Rat Liver Mitochondria. Archives of Medical Research, 46, 597–603.
  • 27. Wang YS., Li YY., Cui W., Li LB., Zhang ZC., Tian BP., Zhang GS., 2017. Melatonin attenuates pain hypersensitivity and decreases astrocytemediated spinal neuroinflammation in a rat model of oxaliplatin-induced pain. Inflammation, 40, 2052-2061.
  • 28. Xia T., Zhang J., Han L., Jin Z., Wang J., Li X., Man S., Liu C., Gao W., 2019. Protective effect of magnolol on oxaliplatin‐induced intestinal injury in mice. Phytotherapy Research, 33, 1161-1172.
  • 29. Yehia R., Saleh S., El Abhar H., Saad AS., Schaalan, M., 2019. L-Carnosine protects against Oxaliplatin-induced peripheral neuropathy in colorectal cancer patients: A perspective on targeting Nrf-2 and NF-κB pathways. Toxicology and applied pharmacology, 365, 41-50.
  • 30. Yesildag K., Gur C., Ileriturk M., Kandemir FM., 2022. Evaluation of oxidative stress, inflammation, apoptosis, oxidative DNA damage and metalloproteinases in the lungs of rats treated with cadmium and carvacrol. Molecular Biology Reports, 49, 1201–1211.
  • 31. Yıldız MO., Çelik H., Caglayan C., Kandemir FM., Gür C., Bayav İ., Genç A., Kandemir, Ö., 2022. Neuromodulatory effects of hesperidin against sodium fluoride-induced neurotoxicity in rats: Involvement of neuroinflammation, endoplasmic reticulum stress, apoptosis and autophagy. NeuroToxicology, 90, 197-204.
There are 30 citations in total.

Details

Primary Language Turkish
Subjects Biochemistry and Cell Biology (Other), Veterinary Sciences
Journal Section Research Articles
Authors

Cihan Gür 0000-0001-6775-7858

Fatih Mehmet Kandemir This is me

Publication Date September 28, 2022
Submission Date May 30, 2022
Published in Issue Year 2022 Volume: 2 Issue: 2

Cite

EndNote Gür C, Kandemir FM (September 1, 2022) Oksaliplatin ve Naringin’in Dalak Dokusu Üzerine Etkilerinin Rat Modelinde Değerlendirilmesi. Laboratuvar Hayvanları Bilimi ve Uygulamaları Dergisi 2 2 72–80.

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