Effects of Panax ginseng on cisplatin-induced testicular damage of rats

Yıl 2021, Cilt: 5 Sayı: 1, 37 - 43, 15.05.2021

Esra Aslan , Kübra Kumalar Hilal Güzel , Hasan Hüseyin Demirel , Sefa Çelik Mehmet Bilgehan Pektaş

https://doi.org/10.30616/ajb.869240

Öz

Infertility has become an increasingly important health problem due to genetic, familial, hormonal, and congenital abnormalities, environmental and chemical reasons. This study aimed to investigate the effects of Panax ginseng (Pnx) root extract on cisplatin (CP) induced testicular damage of rats. Four animal groups were applied with different protocols as Control, Pnx (200 mg / kg), CP (7 mg / kg), and CP + Pnx (200 mg / kg). At the end of the experiment, the body and testicular weights of the rats were measured. While free/total testosterone, total antioxidant capacity (TAC), and total oxidative species (TOS) levels were analyzed in blood samples, apoptotic cells were marked by TUNEL staining in testicular samples of rats. According to the results, free/total testosterone and TAC levels were decreased while TOS levels increased in injured rats' plasma. On the other hand, seminiferous tubule diameters widened, and the number of apoptotic cells increased in rats' testis. These variables were significantly improved with the consumption of Pnx. As a result, Pnx has a significant protective effect on testicular tissue; however, further studies are needed to elucidate its action mechanism.

Anahtar Kelimeler

Apoptosis, Cisplatin, Panax ginseng, TAC, TOS

Destekleyen Kurum

Afyon Kocatepe University Research Fund

Proje Numarası

(17-SAG.BIL-25)

Panax ginseng’in sıçanlarda sisplatin ile oluşturulan testis hasarı üzerine etkileri

Öz

İnfertilite genetik, ailevi, hormonal nedenler, doğumsal anormallikler, çevresel ve kimyasal nedenlerle günümüzde artmakta olan önemli bir sağlık sorunu haline gelmiştir. Bu çalışma ile sıçanlarda sisplatin (CP) ile indüklenen testis hasarı üzerine Panax ginseng (Pnx) kök ekstraktının etkilerinin incelenmesi amaçlanmıştır. Sıçanlar Kontrol, Pnx (200 mg/kg), CP (7 mg/kg) ve CP+Pnx (200 mg/kg) olmak üzere 4 gruba ayrılmıştır. Deney sonunda sıçanların vücut ve testis ağırlıkları ölçülmüştür. Sıçanların kan örneklerinde serbest/total testosteron, toplam antioksidan kapasite (TAK) ve toplam oksidan durum (TOD) seviyeleri analiz edilirken, testis örneklerinde TUNEL boyaması ile apoptotik hücreler işaretlenmiştir. Sonuçlara göre hasar oluşturulmuş sıçanların plazma örneklerinde serbest/total testosteron ve TAK düzeyleri azalırken, TOD miktarı artmıştır. Testis dokularında seminifer tübül çapları genişlemiş ve apoptotik hücre sayısı artmıştır. Pnx uygulaması ile bu değişkenlerin ciddi oranda düzeldiği saptanmıştır. Sonuç olarak, Pnx’in testiküler dokuda belirgin koruyucu etkinliği bulunmaktadır; fakat etki mekanizmasının aydınlatılabilmesi için ileri çalışmalara gereksinim vardır.

Anahtar Kelimeler

Cisplatin, Panax ginseng, Apoptoz, TAK, TOD

Proje Numarası

(17-SAG.BIL-25)

Kaynakça

• Aksu EH, Kandemir FM, Altun S, Küçükler S, Çomaklı S, Ömür AD (2016). Ameliorative effect of carvacrol on cisplatin-induced reproductive damage in male rats. Journal of Biochemical and Molecular Toxicology 30(10): 513-520.
• Aly HAA, Eid BG (2020). Cisplatin-induced testicular damage through mitochondria-mediated apoptosis, inflammation and oxidative stress in rats: Impact of resveratrol. Endocrine Journal 67(9): 969-980.
• Azab SS, Kamel I, Ismai, NN, El Din Hosni H, El Fatah MA (2020). The defensive role of taurine against gonadotoxicity and testicular apoptosis effects induced by cisplatin in rats. Journal of Infection and Chemotherapy 26(1): 51-57.
• Barabas K, Milner R, Lurie D, Adin C (2008). Cisplatin: A review of toxicities and therapeutic applications. Veterinary and Comparative Oncology 6(1): 1-18.
• Ceylan T, Kaymak E, Cantürk F, Yakan B (2020). Research on the protective effect of caffeic acid phenethyl ester on testicular damage caused by cisplatin. Turkish Journal of Medical Sciences 50(8): 2032-2039.
• Dasari S, Bernard TP (2014). Cisplatin in cancer therapy: Molecular mechanisms of action. European Journal of Pharmacology 740: 364-378.
• De Freitas AT, Figueiredo PC, de Aquino AM, Fernandes AH, Fantin DR, Justulin LA, Scarano WR (2019). Panax ginseng metabolite (GIM-1) prevents oxidative stress and apoptosis in human Sertoli cells exposed to Monobutyl-phthalate (MBP). Reproductive Toxicology 86: 68-75.
• Erel O (2004). A novel automated method to measure total antioxidant response against potent free radical reactions. Clinical Biochemistry 37(2): 112-119.
• Erel O (2005). A new automated colorimetric method for measuring total oxidant status. Clinical Biochemistry 38(12): 1103-1111.
• Famurewa AC, Ekeleme-Egedigwe CA, Onwe CS, Egedigwe UO, Okoro CO, Egedigwe UJ, Asogwa NT (2020).
• Ginger juice prevents cisplatin-induced oxidative stress, endocrine imbalance and NO/iNOS/NF-κB signalling via modulating testicular redox-inflammatory mechanism in rats. Andrologia 52(10): 1-10.
• Geyikoğlu F, Çolak S, Türkez H, Bakır M, Koç K, Hosseinigouzdagani MK, Çeriğ S, Sönmez M (2017). Oleuropein ameliorates cisplatin-induced hematological damages via restraining oxidative stress and DNA injury. Indian Journal of Hematology and Blood Transfusion 33(3): 348-354.
• Hanigan MH, Devarajan P (2003). Cisplatin nephrotoxicity: molecular mechanisms. Cancer Therapy 1: 47-61.
• Johnsen SG (1970). Testicular biopsy score count – A method for registration of spermatogenesis in human testes: normal values and results in 335 hypogonadal males. Hormone Research in Paediatrics 1(1): 2-25.
• Jourabi F, Yari S, Amiri P, Heidarianpour A, Hashemi H (2020). The ameliorative effects of methylene blue on testicular damage induced by cisplatin in rats. Andrologia 53(1): e13850.
• Kim IH, Kim SK, Kim EH, Kim SW, Sohn SH, Lee SC, Choi SD, Pyo SN, Rhee DK (2011). Korean red ginseng up-regulates C21-steroid hormone metabolism via Cyp11a1 gene in senescent rat testes. Journal of Ginseng Research 35(3): 272-282.
• Kim MK, Cha KM, Hwang SY, Park UK, Seo SK, Lee SH, Jeong MS, Cho S, Kopalli SR, Kim SK (2017). Pectinase-treated Panax ginseng protects heat stress-induced testicular damage in rats. Reproduction 153(6): 737-747.
• Kim YO, Lee HY, Won H, Nah SS, Lee HY, Kim HK, Kwon JT, Kim HJ (2015). Influence of Panax ginseng on the offspring of adult rats exposed to prenatal stress. International Journal of Molecular Medicine 35(1): 103-109.
• Kohsaka T, Minagawa I, Morimoto M, Yoshida T, Sasanami T, Yoneda Y, Ikegaya N, Sasada H (2020). Efficacy of relaxin for cisplatin-induced testicular dysfunction and epididymal spermatotoxicity. Basic and Clinical Andrology 30(1): 1-13.
• Kong D, Zhang J, Hou X, Zhang S, Tan J, Chen Y, Yang W, Zeng J, Han Y, Liu X, Xu D, Cai R (2017). Acetamiprid inhibits testosterone synthesis by affecting the mitochondrial function and cytoplasmic adenosine triphosphate production in rat Leydig cells†. Biology of Reproduction 96(1): 254-265.
• Kopalli SR, Cha KM, Jeong MS, Lee SH, Sung JH, Seo SK, Kim SK (2016). Pectinase-treated Panax ginseng ameliorates hydrogen peroxide-induced oxidative stress in GC-2 sperm cells and modulates testicular gene expression in aged rats. Journal of Ginseng Research 40(2): 185-195.
• Kumar M, Sharma MK, Saxena PS, Kumar A (2003). Radioprotective effect of Panax ginseng on the phosphatases and lipid peroxidatiAksu EH, Kandemir FM, Altun S, Küçükler S, Çomaklı S, Ömür AD (2016). Ameliorative effect of carvacrol on cisplatin-induced reproductive damage in male rats. Journal of Biochemical and Molecular Toxicology 30(10): 513-520.
• Aly HAA, Eid BG (2020). Cisplatin-induced testicular damage through mitochondria-mediated apoptosis, inflammation and oxidative stress in rats: Impact of resveratrol. Endocrine Journal 67(9): 969-980.
• Azab SS, Kamel I, Ismai, NN, El Din Hosni H, El Fatah MA (2020). The defensive role of taurine against gonadotoxicity and testicular apoptosis effects induced by cisplatin in rats. Journal of Infection and Chemotherapy 26(1): 51-57.
• Barabas K, Milner R, Lurie D, Adin C (2008). Cisplatin: A review of toxicities and therapeutic applications. Veterinary and Comparative Oncology 6(1): 1-18.
• Ceylan T, Kaymak E, Cantürk F, Yakan B (2020). Research on the protective effect of caffeic acid phenethyl ester on testicular damage caused by cisplatin. Turkish Journal of Medical Sciences 50(8): 2032-2039.
• Dasari S, Bernard TP (2014). Cisplatin in cancer therapy: Molecular mechanisms of action. European Journal of Pharmacology 740: 364-378.
• De Freitas AT, Figueiredo PC, de Aquino AM, Fernandes AH, Fantin DR, Justulin LA, Scarano WR (2019). Panax ginseng metabolite (GIM-1) prevents oxidative stress and apoptosis in human Sertoli cells exposed to Monobutyl-phthalate (MBP). Reproductive Toxicology 86: 68-75.
• Erel O (2004). A novel automated method to measure total antioxidant response against potent free radical reactions. Clinical Biochemistry 37(2): 112-119.
• Erel O (2005). A new automated colorimetric method for measuring total oxidant status. Clinical Biochemistry 38(12): 1103-1111.
• Famurewa AC, Ekeleme-Egedigwe CA, Onwe CS, Egedigwe UO, Okoro CO, Egedigwe UJ, Asogwa NT (2020). Ginger juice prevents cisplatin-induced oxidative stress, endocrine imbalance and NO/iNOS/NF-κB signalling via modulating testicular redox-inflammatory mechanism in rats. Andrologia 52(10): 1-10.
• Geyikoğlu F, Çolak S, Türkez H, Bakır M, Koç K, Hosseinigouzdagani MK, Çeriğ S, Sönmez M (2017). Oleuropein ameliorates cisplatin-induced hematological damages via restraining oxidative stress and DNA injury. Indian Journal of Hematology and Blood Transfusion 33(3): 348-354.
• Hanigan MH, Devarajan P (2003). Cisplatin nephrotoxicity: molecular mechanisms. Cancer Therapy 1: 47-61.
• Johnsen SG (1970). Testicular biopsy score count – A method for registration of spermatogenesis in human testes: normal values and results in 335 hypogonadal males. Hormone Research in Paediatrics 1(1): 2-25.
• Jourabi F, Yari S, Amiri P, Heidarianpour A, Hashemi H (2020). The ameliorative effects of methylene blue on testicular damage induced by cisplatin in rats. Andrologia 53(1): e13850.
• Kim IH, Kim SK, Kim EH, Kim SW, Sohn SH, Lee SC, Choi SD, Pyo SN, Rhee DK (2011). Korean red ginseng up-regulates C21-steroid hormone metabolism via Cyp11a1 gene in senescent rat testes. Journal of Ginseng Research 35(3): 272-282.
• Kim MK, Cha KM, Hwang SY, Park UK, Seo SK, Lee SH, Jeong MS, Cho S, Kopalli SR, Kim SK (2017). Pectinase-treated Panax ginseng protects heat stress-induced testicular damage in rats. Reproduction 153(6): 737-747.
• Kim YO, Lee HY, Won H, Nah SS, Lee HY, Kim HK, Kwon JT, Kim HJ (2015). Influence of Panax ginseng on the offspring of adult rats exposed to prenatal stress. International Journal of Molecular Medicine 35(1): 103-109.
• Kohsaka T, Minagawa I, Morimoto M, Yoshida T, Sasanami T, Yoneda Y, Ikegaya N, Sasada H (2020). Efficacy of relaxin for cisplatin-induced testicular dysfunction and epididymal spermatotoxicity. Basic and Clinical Andrology 30(1): 1-13.
• Kong D, Zhang J, Hou X, Zhang S, Tan J, Chen Y, Yang W, Zeng J, Han Y, Liu X, Xu D, Cai R (2017). Acetamiprid inhibits testosterone synthesis by affecting the mitochondrial function and cytoplasmic adenosine triphosphate production in rat Leydig cells†. Biology of Reproduction 96(1): 254-265.
• Kopalli SR, Cha KM, Jeong MS, Lee SH, Sung JH, Seo SK, Kim SK (2016). Pectinase-treated Panax ginseng ameliorates hydrogen peroxide-induced oxidative stress in GC-2 sperm cells and modulates testicular gene expression in aged rats. Journal of Ginseng Research 40(2): 185-195.
• Kumar M, Sharma MK, Saxena PS, Kumar A (2003). Radioprotective effect of Panax ginseng on the phosphatases and lipid peroxidation level in testes of Swiss albino mice. Biological and Pharmaceutical Bulletin 26(3): 308-312.
• Liu HC, Zhu D, Wang C, Guan H, Li S, Hu C, Chen Z, Hu Y, Lin H, Lian QQ, Ge RS (2015). Effects of etomidate on the steroidogenesis of rat immature Leydig cells. PLoS One 10(11): e0139311.
• Lonare M, Kumar M, Raut, S, More A, Doltade S, Badgujar P, Telang A (2016). Evaluation of ameliorative effect of curcumin on imidacloprid-induced male reproductive toxicity in Wistar rats. Environmental Toxicology 31(10): 1250-1263.
• Majd EN, Hajirahimi A, Tabandeh MR, Molaei R (2021). Protective effects of green and chemical zinc oxide nanoparticles on testis histology, sperm parameters, oxidative stress markers and androgen production in rats treated with cisplatin. Cell and Tissue Research (online 12 Jan 2021).
• Mancuso C, Santangelo R (2017). Panax ginseng and Panax quinquefolius : From pharmacology to toxicology. Food and Chemical Toxicology 107: 362-372.
• Rashid K, Sinha K, Sil PC (2013). An update on oxidative stress-mediated organ pathophysiology. Food and Chemical Toxicology 62: 584-600.
• Saad KM, Abdelrahman RS, Said E (2020). Mechanistic perspective of protective effects of nilotinib against cisplatin-induced testicular injury in rats: Role of JNK/caspase-3 signaling inhibition. Environmental Toxicology and Pharmacology 76: 103334.
• Saad SY, Najjar TA, Alashari M (2004). Role of non-selective adenosine receptor blockade and phosphodiesterase inhibition in cisplatin-induced nephrogonadal toxicity in rats. Clinical and Experimental Pharmacology and Physiology 31(12): 862-867.
• Sadeghi F, Etebari M, Habibi-Roudkenar M, Jahanian-Najafabadi A (2018). Lipocalin2 protects human embryonic kidney cells against cisplatin-induced genotoxicity. Iranian Journal of Pharmaceutical Research : IJPR 17(1): 147-154.
• Sadi G, Sadi Ö (2010). Antioxidants and regulation of antioxidant enzymes by cellular redox status. Turkish Journal and Scientific Reviews 3(2): 95-107.
• Wang L, He Y, Li Y, Pei C, Olatunji OJ, Tang J, Famurewa AC, Wang H, Yan B (2020). Protective effects of nucleosides-rich extract from cordyceps cicadae against cisplatin induced testicular damage. Chemistry and Biodiversity 17(11): e2000671.
• Wang PT, Sudirman S, Hsieh MC, Hu JY, Kong ZL (2020). Oral supplementation of fucoxanthin-rich brown algae extract ameliorates cisplatin-induced testicular damage in hamsters. Biomedicine and Pharmacotherapy 125: 109992.
• Yucel C, Arslan FD, Ekmekci S, Ulker V, Kisa E, Erdogan-Yucel E, Ucar M, Ilbey YO, Celik O, Basok BI, Kozacioglu Z (2019). Protective effect of all-trans retinoic acid in cisplatin-induced testicular damage in rats. The World Journal of Men’s Health 37(2): 249-256.
• Zhang K, Weng H, Yang J, Wu C (2020). Protective effect of Liuwei Dihuang Pill on cisplatin-induced reproductive toxicity and genotoxicity in male mice. Journal of Ethnopharmacology 247: 112269.
• Zhu D, Fang X, Chen Y, Shan M, Jiang R, Qiu Z, Luo H (2020). Structure-activity relationship analysis of Panax ginseng glycoproteins with cytoprotective effects using LC-MS/MS and bioinformatics. International Journal of Biological Macromolecules 158: 1352-1361.