Efecto protector del propóleo sobre las actividades de las enzimas antioxidantes, las características de los espermatozoides epididimarios y la estructura histopatológica de los testículos de ratas tratadas con ciclofosfamida

  • Emre Kaya Firat University, Faculty of Veterinary Medicine, Department of Biochemistry. Elazig, Türkiye
  • Seval Yılmaz Firat University, Faculty of Veterinary Medicine, Department of Biochemistry. Elazig, Türkiye
  • Zülal Altay Firat University, Faculty of Veterinary Medicine, Department of Biochemistry. Elazig, Türkiye
  • Şeyma Özer Kaya Firat University, Faculty of Veterinary Medicine, Department of Reproduction and Artificial Insemination. Elazig, Türkiye
  • Neriman Çolakoğlu Firat University, Faculty of Medicine, Department of Histology and Embryology, Elazig, Türkiye
  • Emine Sarman Afyonkarahisar Health Sciences University, Faculty of Medicine, Department of Histology and Embryology. Afyon, Türkiye
Palabras clave: Antioxidante, ciclofosfamida, malondialdehído, estrés oxidativo, propóleos

Resumen

El objetivo de este estudio fue evaluar el posible efecto terapéutico del propóleo sobre la peroxidación lipídica testicular inducida por ciclofosfamida (CP) y sobre los cambios asociados en los parámetros espermatológicos en los espermatozoides epididimarios y la estructura histopatológica de los testículos de rata. Las ratas se separaron aleatoriamente en 4 grupos con 7 ratas en cada grupo. Se formaron grupos como; 1er grupo: grupo control (ratas no tratadas), 2do grupo: grupo tratado con propóleo, 3er grupo: grupo tratado con CP y 4to grupo: grupo tratado con CP+propóleo. Se administró propóleo a las ratas en una dosis de 200 mg·kg pc -1 mediante alimentación forzada durante 7 días (d). Se administró CP a las ratas en una dosis única de 150 mg·kg pc -1 por vía intraperitoneal. La administración de propóleo se inició 2 días antes de la administración de CP y continuó durante 7 días. Niveles de malondialdehído (MDA) y glutatión reducido (GSH), actividades de catalasa (CAT), glutatión peroxidasa (GSH–Px), glutatión S–transferasa (GST) y superóxido dismutasa (SOD), parámetros espermatológicos, peso de los órganos reproductivos . y se calcula la estructura histopatológica. En comparación con el grupo de control, los niveles de MDA y las actividades de SOD aumentan significativamente; Si bien las actividades CAT y GST disminuyeron, no se encontraron cambios en los niveles de GSH y las actividades GSH–Px en el grupo CP. En el grupo tratado con CP, hubo una disminución en la motilidad de los espermatozoides del epidídimo, la densidad de los espermatozoides en los espermatozoides del epidídimo y el peso de los testículos, la próstata, el epidídimo y la vesícula seminal; mientras que hubo un aumento en la proporción de espermatozoides anormales en comparación con el grupo de control en los espermatozoides epididimarios. El propóleo normalizó los parámetros bioquímicos y espermatológicos en los espermatozoides epididimarios. El examen histopatológico del tejido testicular mostró que los cambios histopatológicos más significativos, como restos celulares, invaginación y degeneración, ocurrieron en el grupo CP. En la patogénesis de la toxicidad testicular inducida por la PC puede desempeñar un papel el deterioro del equilibrio oxidante-antioxidante y el propóleo puede reducir los efectos secundarios graves de las alteraciones inducidas por la PC.

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Citas

Ralhan R, Kaur J. Alkylating agents and cancer therapy. Exp. Op. Therap. Patents. [Internet]. 2007; 17(9):1061–1075. doi: https://doi.org/c4gxbz

Queirós V, Azeiteiro UM, Soares AMVM, Freitas R. The antineoplastic drugs cyclophosphamide and cisplatin in the aquatic environment–Review. J. Hazardous Materials. [Internet]. 2021; 412:125028. doi: https://doi.org/mhxs

Ghobadi E, Moloudizargari M, Asghari MH, Abdollahi M. The mechanisms of cyclophosphamide–induced testicular toxicity and the protective agents. Expert Opin. Drug Metab. Toxicol. [Internet]. 2017; 13(5):525–536. doi: https://doi.org/gm4jt2

Prasad R, Giri S, Singh AK, Singh I. 15–deoxy–delta12, 14–prostaglandin J2 attenuates endothelial–monocyte interaction: implication for inflammatory diseases. J. Inflamm. [Internet]. 2008; 5(1):1–10. doi: https://doi.org/c9grdg

Povirk LF, Shuker DE. DNA damage and mutagenesis induced by nitrogen mustards. Mutat Res. [Internet]. 1994; 318(3):205–226. doi: https://doi.org/frxr6t

Wang L, Albasi C, Faucet–Marquis V, Pfohl–Leszkowicz A, Dorandeu C, Marion B, Causserand C. Cyclophosphamide removal from water by nanofiltration and reverse osmosis membrane. Water Res. [Internet]. 2009; 43(17):4115–4122. doi: https://doi.org/fqtnkr

Souid AK, Tacka KA, Galvan KA, Penefsky HS. Immediate effects of anticancer drugs on mitochondrial oxygen consumption. Biochem. Pharmacol. [Internet]. 2003; 66(6):977–987. doi: https://doi.org/b6hf7r

Türk, G. [Adverse effects of chemotherapeutics on male reproductive system, and protective strategies]. Marmara Pharm J. [Internet]. 2013 [cited 20 Aug 2023]; 17(2):73–92. Turkish. Available in: https://goo.su/myzX

Anan HH, Zidan RA, Abd EL–Baset SA, Ali MM. Ameliorative effect of zinc oxide nanoparticles on cyclophosphamide induced testicular injury in adult rat. Tissue Cell. [Internet]. 2018; 54:80–93. doi: https://doi.org/gff4tw

Ghosh D, Das UB, Misro M. Protective role of α–tocopherol–succinate (provitamin–E) in cyclophosphamide induced testicular gametogenic and steroidogenic disorders: a correlative approach to oxidative stress. Free Radic. Res. [Internet]. 2002; 36(11):1209–1218. doi: https://doi.org/bdq2rk

Das UB, Mallick M, Debnath JM, Ghosh, D. Protective effect of ascorbic acid on cyclophosphamide–induced testicular gametogenic and androgenic disorders in male rats. Asian J. Androl. 2002; 4(3):201–207. Cited in PUBMED; PMID 12364977.

Haque R, Bin–Hafeez B, Ahmad I, Parvez S, Pandey S, Raisuddin S. Protective effects of Emblica officinalis Gaertn. in cyclophosphamide–treated mice. Hum. Exp. Toxicol. [Internet]. 2001; 20(12):643–650. doi: https://doi.org/fgrpkd

Harel S, Fermé C, Poirot C. Management of fertility in patients treated for Hodgkin’s lymphoma. Haematol. [Internet]. 2011; 96(11):1692–1699. doi: https://doi.org/c2zbs6

Wieczorek PP, Hudz N, Yezerska O, Horčinová–Sedláčková V, Shanaida M, Korytniuk O, Jasicka–Misiak I. Chemical variability and pharmacological potential of propolis as a source for the development of new pharmaceutical products. Molec. [Internet]. 2022; 27(5):1–28. doi: https://doi.org/mhx4

Toreti VC, Sato HH, Pastore GM, Park YK. Recent progress of propolis for its biological and chemical compositions and its botanical origin. Evid. Based Complement. Alternat. Med. [Internet]. 2013; 2013:697390. doi: https://doi.org/f98qm5

Kaya E, Yılmaz S, Çolakoğlu N. [The protective role of propolis in cyclophosphamide–induced cardiotoxicity in rats]. Ankara Univ. Vet. Fak. Derg. [Internet]. 2019 [cited 15 Oct 2023]; 66(1):13–20.Turkish. Available in: https://goo.su/qHoI7

Rizk SM, Zaki HF, Mina MA. Propolis attenuates doxorubicin–induced testicular toxicity in rats. Food Chem. Toxicol. [Internet]. 2014; 67:176–186. doi: https://doi.org/f53g96

Famurewa AC, Edeogu CO, Offor FI, Besong EE, Akunna GG, Maduagwuna EK. Downregulation of redox imbalance and iNOS/NF–ĸB/caspase–3 signalling with zinc supplementation prevents urotoxicity of cyclophosphamide–induced hemorrhagic cystitis in rats. Life Sci. [Internet]. 2021; 266:118913. doi: https://doi.org/gjtb7c

Placer ZA, Cushman L, Johnson BC. Estimation of products of lipid peroxidation in biological fluids. Anal. Biochem. [Internet]. 1966; 16:359–364. doi: https://doi.org/b96rpj

Ellman GL, Courtney KD, Andres Jr V, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. [Internet]. 1961; 7(2):88–95. doi: https://doi.org/fwdkkz

Aebi H. Catalase. In: Bergmeyer HU, editor. Methods of Enzymatic Analysis. 2nd ed. Vol. 2. [Internet]. Hoboken, NJ, USA: Verlag Chemie; 1974. p. 673–678. doi: https://doi.org/gj9cbj

Beutler E. Red Cell Metabolism. A Manual of Biochemical Methods. 3rd ed. Orlando, FL, USA: Grune & Stratton; 1984. p. 310–311.

Habig WH, Pabst MJ, Jakoby WB. Glutathione S–transferases: The first enzymatic step in mercapturic acid formation. J. Biol. Chem. [Internet]. 1974; 249(22):7130–7139. doi: https://doi.org/gjjzqq

Sun YI, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin. Chem. [Internet]. 1988; 34(3):497–500. doi: https://doi.org/gj74fn

Lowry O, Rosebrough N, Farr AL, Randall R. Protein measurement with the Folin phenol reagent. J. Biol. Chem. [Internet]. 1951; 193(1):265–275. doi: https://doi.org/ghv6nr

Türk G, Sönmez M, Aydin M, Yüce A, Gür S, Yüksel M, Aksu EH, Aksoy H. Effects of pomegranate juice consumption on sperm quality, spermatogenic cell density, antioxidant activity and testosterone level in male rats. Clin. Nutr. [Internet]. 2008; 27(2):289–296. doi: https://doi.org/ckgm8f

Bancroft JD, Gamble M. Theory and Practice of Histological Techniques. 5th ed. London, England: Churchill Livingstone Publishing; 2002. 725 p.

Bukowski K, Kciuk M, Kontek R. Mechanisms of multidrug resistance in cancer chemotherapy. Intern. J. Molec. Sci. [Internet]. 2020; 21(9):3233. doi: https://doi.org/gnc5wx

Gómez–Figueroa E, Gutierrez–Lanz E, Alvarado–Bolaños A, Casallas–Vanegas A, Garcia–Estrada C, Zabala–Angeles I, Cadena–Fernandez A, Veronica RA, Irene TF, Flores–Rivera, J. Cyclophosphamide treatment in active multiple sclerosis. Neurol. Sci. [Internet]. 2021; 42:3775–3780. doi: https://doi.org/mhzd

Caglayan C. The effects of naringin on different cyclophosphamide–induced organ toxicities in rats: investigation of changes in some metabolic enzyme activities. Environ. Sci. Pollut. Res. Int. [Internet]. 2019; 26(26):26664–26673. doi: https://doi.org/mhzf

Sinanoglu O, Yener AN, Ekici S, Midi A, Aksungar FB. The protective effects of spirulina in cyclophosphamide induced nephrotoxicity and urotoxicity in rats. Urol. [Internet]. 2012; 80(6):e1392. doi: https://doi.org/f2fj2g

Çeribaşi AO, Türk G, Sönmez M, Sakin F, Ateşşahin A. Toxic effect of cyclophosphamide on sperm morphology, testicular histology and blood oxidant‐antioxidant balance, and protective roles of lycopene and ellagic acid. Basic Clin. Pharmacol. Toxicol. [Internet]. 2010; 107(3):730–736. doi: https://doi.org/fv8pv5

Sadeghzadeh F, Sadeghzadeh A, Changizi–Ashtiyani S, Bakhshi S, Mashayekhi FJ, Mashayekhi M, Poorcheraghi H, Zarei A, Jafari M. The effect of hydro–alcoholic extract of Ceratonia Silique L. on spermatogenesis index in rats treated with cyclophosphamide: An experimental study. Int. J. Reprod. Biomed. [Internet]. 2020; 18(4):295–306. doi: https://doi.org/mhzq

Mahmoud AM, Germoush MO, Alotaibi MF, Hussein OE. Possible involvement of Nrf2 and PPARγ up–regulation in the protective effect of umbelliferone against cyclophosphamide–induced hepatotoxicity. Biomed. Pharmacother. [Internet]. 2017; 86:297–306. doi: https://doi.org/f9trdv

Nafees S, Rashid S, Ali N, Hasan SK, Sultana S. Rutin ameliorates cyclophosphamide induced oxidative stress and inflammation in Wistar rats: role of NFκB/MAPK pathway. Chem. Biol. Interact. [Internet]. 2015; 231:98–107. doi: https://doi.org/f7bdt5

El–Naggar SA, Alm–Eldeen AA, Germoush MO, El–Boray KF, Elgebaly HA. Ameliorative effect of propolis against cyclophosphamide–induced toxicity in mice. Pharm. Biol. [Internet]. 2015; 53(2):235–241. doi: https://doi.org/mhzr

Akyol S, Gulec MA, Erdemli HK, Akyol O. Can propolis and caffeic acid phenethyl ester be promising agents against cyclophosphamide toxicity? J. Intercult. Ethnopharmacol. [Internet]. 2016; 5(1):105–107. doi: https://doi.org/gjk6m8

Kaya E, Yılmaz S, Ceribasi S. Protective role of propolis on low and high dose furan–induced hepatotoxicity and oxidative stress in rats. J. Vet. Res. [Internet]. 2019; 63(3):423–431. doi: https://doi.org/mhzs

Ramos Melo NDO, Peres Júnior HDS, Diniz CA, Silva MDS, Gomes de Lemos TL, Jamacaru FVF, Dornelas CA. Red propolis reduces inflammation in cyclophosphamide–induced hemorrhagic cystitis in rats. BioMed. [Internet]. 2022; 42(2):253–263. doi: https://doi.org/mhzt

Van der Kaaij MA, van Echten‐Arends J, Simons AH, Kluin‐Nelemans HC. Fertility preservation after chemotherapy for Hodgkin lymphoma. Hematol. Oncol. [Internet]. 2010; 28(4):168–179. doi: https://doi.org/b7mrs9

Levy MJ, Stillman RJ. Reproductive potential in survivors of childhood malignancy. Pediatrician. 1991; 18(1):61–70.

Aslam I, Fishel S, Moore H, Dowell K, Thornton, S. Fertility preservation of boys undergoing anti–cancer therapy: a review of the existing situation and prospects for the future. Hum. Reprod. [Internet]. 2000; 15(10):2154–2159. doi: https://doi.org/btwhvp

Kenney LB, Laufer MR, Grant FD, Grier H, Diller L. High risk of infertility and long term gonadal damage in males treated with high dose cyclophosphamide for sarcoma during childhood. Cancer. [Internet]. 2001; 91(3):613–621. doi: https://doi.org/ddmtfr

Meistrich ML, Wilson G, Brown BW, Da Cunha MF, Lipshultz LI. Impact of cyclophosphamide on long‐term reduction in sperm count in men treated with combination chemotherapy for Ewing and soft tissue sarcomas. Cancer. [Internet]. 1992; 70(11):2703–2712. doi: https://doi.org/bkxkr8

Ragheb AM, Sabanegh Jr ES. Male fertility–implications of anticancer treatment and strategies to mitigate gonadotoxicity. Anti–Cancer Agents Med. Chem. [Internet]. 2010; 10(1):92–102. doi: https://doi.org/mhz5

Ilbey YO, Ozbek E, Simsek A, Otunctemur A, Cekmen M, Somay A. Potential chemoprotective effect of melatonin in cyclophosphamide–and cisplatin–induced testicular damage in rats. Fert. Steril. [Internet]. 2009; 92(3):1124–1132. doi: https://doi.org/c4s44m

Ghosh D, Das UB, Ghosh S, Mallick M, Debnath J. Testicular gametogenic and steroidogenic activities in cyclophosphamide treated rat: a correlative study with testicular oxidative stress. Drug Chem. Toxicol.[Internet]. 2002; 25(3):281–292. doi: https://doi.org/dwbt3p

Codrington AM, Hales BF, Robaire B. Chronic cyclophosphamide exposure alters the profile of rat sperm nuclear matrix proteins. Biol. Reprod. [Internet]. 2007; 77(2):303–311. doi: https://doi.org/cw9d88

Codrington AM, Hales BF, Robaire B. Exposure of male rats to cyclophosphamide alters the chromatin structure and basic proteome in spermatozoa. Hum. Reprod. [Internet]. 2007; 22(5):1431–1442. doi: https://doi.org/c7bjxs

Codrington AM, Hales BF, Robaire B. Spermiogenic germ cell phase–specific DNA damage following cyclophosphamide exposure. J. Androl. [Internet]. 2004; 25(3):354–362. doi: https://doi.org/mhz7

Elangovan N, Chiou TJ, Tzeng WF, Chu ST. Cyclophosphamide treatment causes impairment of sperm and its fertilizing ability in mice. Toxicol. [Internet]. 2006; 222(1–2):60–70. doi: https://doi.org/brg4pt

Sakr SA, Mahran HA, Abo–El–Yazid SM. Effect of fenugreek seeds extract on cyclophosphamide–induced histomorphometrical, ultrastructural and biochemical changes in testes of albino mice. Toxicol. Industr. Health. [Internet]. 2012; 28(3):276–288. doi: https://doi.org/bgzcrc

Conklin KA. Cancer chemotherapy and antioxidants. J. Nutr. [Internet]. 2004; 134(11):3201–3204. doi: https://doi.org/mhz8

Cengiz M, Sahinturk V, Yildiz SC, Şahin İK, Bilici N, Yaman SO, Altuner Y, Appak–Baskoy S, Ayhanci, A. Cyclophosphamide induced oxidative stress, lipid per oxidation, apoptosis and histopathological changes in rats: Protective role of boron. J. Trace Elem. Med. Biol. [Internet]. 2020; 62:126574. doi: https://doi.org/gm4jt7

Halliwell B, Chirico S. Lipid peroxidation: its mechanism, measurement, and significance. Am J. Clin. Nutr. [Internet]. 1993; 57(5):715–725. doi: https://doi.org/gj74fp

Alkhalaf MI, Alansari WS, Alshubaily FA, Alnajeebi AM, Eskandrani AA, Tashkandi M. A, Babteen NA. Chemoprotective effects of inositol hexaphosphate against cyclophosphamide–induced testicular damage in rats. Sci. Rep. [Internet]. 2020; 10(1):12599. https://doi.org/kp6d

Vaisheva F, Delbes G, Hales BF, Robaire B. Effects of the chemotherapeutic agents for non‐hodgkin lymphoma, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), on the male rat reproductive system and progeny outcome. J. Androl. [Internet]. 2007; 28(4):578–587. doi: https://doi.org/cwfrcj

Sönmez MF, Çilenk KT, Karabulut D, Ünalmış S, Deligönül E, Öztürk İ, Kaymak E. Protective effects of propolis on methotrexate–induced testis injury in rat. Biomed. Pharmacother. [Internet]. 2016; 79:44–51. doi: https://doi.org/f8g83s

Baykalir BG, Seven PT, Gur S, Seven I. The effects of propolis on sperm quality, reproductive organs and testicular antioxidant status of male rats treated with cyclosporine–A. Anim. Rep. [Internet]. 2018; 13(2): 105–111. doi: https://doi.org/f8s4zz

Seven I, Tatli Seven P, Gul Baykalir B, Parlak Ak T, Ozer Kaya S, Yaman M. Bee glue (propolis) improves reproductive organs, sperm quality and histological changes and antioxidant parameters of testis tissues in rats exposed to excess copper. Androl. [Internet]. 2020; 52(4):e13540. doi: https://doi.org/mh2f

Yousef MI, Salama AF. Propolis protection from reproductive toxicity caused by aluminium chloride in male rats. Food Chem. Toxicol. [Internet]. 2009; 47(6):1168–1175. doi: https://doi.org/bwzqt7

Attia AA, ElMazoudy RH, El–Shenawy NS. Antioxidant role of propolis extract against oxidative damage of testicular tissue induced by insecticide chlorpyrifos in rats. Pest. Biochem. Physiol. [Internet]. 2012; 103(2):87–93. doi: https://doi.org/mh2g

Seven PT, Seven I, Karakus S, Mutlu SI, Kaya SO, Arkali G, Ilgar M, Sahin YM, Ismik D, Kilislioglu A. The in–vivo assessment of Turkish propolis and its nano form on testicular damage induced by cisplatin. J. Integr Med. [Internet]. 2021; 19(5):451–459. https://doi.org/mh2h

Yilmaz S, Kandemir FM, Kaya E, Ozkaraca, M. Chemoprotective effects of propolis on aflatoxin b1–induced hepatotoxicity in rats: Oxidative damage and hepatotoxicity by modulating TP53, oxidative stress. Curr. Prot. [Internet]. 2020; 17(3):191–199. doi: https://doi.org/mh2j

Publicado
2024-02-28
Cómo citar
1.
Kaya E, Yılmaz S, Altay Z, Kaya Şeyma Özer, Çolakoğlu N, Sarman E. Efecto protector del propóleo sobre las actividades de las enzimas antioxidantes, las características de los espermatozoides epididimarios y la estructura histopatológica de los testículos de ratas tratadas con ciclofosfamida. Rev. Cient. FCV-LUZ [Internet]. 28 de febrero de 2024 [citado 19 de abril de 2024];34(1):9. Disponible en: https://produccioncientificaluz.org/index.php/cientifica/article/view/41701
Sección
Medicina Veterinaria