Effect of the rutin on azathioprine-induced toxicity in reproductive function male rats
  • Article Type: Research Article
  • Eurasian Journal of Biosciences, 2020 - Volume 14 Issue 2, pp. 4637-4644
  • Published Online: 30 Oct 2020
  • Open Access Full Text (PDF)

Abstract

The current examination directed to research the defensive capability of flavonoid Rutin (Rt) against Azathioprine (AZA)- incited testicular and epididymal injury in experimental male rats. Sixty grown-up male rodents were partitioned into six gatherings. Control gathering (C): was given distiller water orally, The first animals gathering (T1): was treated as a dose of (2.5) mg/kg bw of Azathioprine, Second treatment gathering (T2): received oral gavage (50) mg/kg of Rutin only, Third treatment gathering (T3): was given with (2.5) mg/kg Azathioprine with Rutin at portion 50 mg/kg bw in combination, Fourth treatment gathering (T4): was given Azathioprine orally at 2.5 mg/kg body weight for month and afterward Rutin oral given at a dose of 50 mg/kg toward the finish of the analysis, Fifth treatment gathering (T5):was given Rutin orally at 50 mg/kg of body weight for month and afterward Azathioprine oral given at a dose of 2.5 mg/kg toward the finish of the test. Results indicated that AZA caused a significantly decline (P<0.05) in plasma luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone levels which significantly increased as a result of co-treatment with rutin. Likewise, the co-treatment of these animals with rutin, produced a potential increase of the spermatogenesis in testes, epididymal sperm count, ability of motility, viability and percentage of morphology, are lowered in AZA administered, as compared to normal control. Rutin inhibited oxidative damage in each of testis and epididymis of AZA-treated experimental rats. The rutin treatment may decrease AZA-stimulated male reproductive injury as a powerful antioxidant component. The results proved treating with rutin lessen damaging effects of AZA therapy by reduction of the generating ROS and ameliorate reproductive toxicity in male rats, by restoring normal spermatogenesis, and hormones levels. Consuming of foods that contain rutin might be deem as an alternative and advantageous way to safeguard male fertility from chemotherapy-induced reproductive injury.

References

  • Abarikwu S O, Akiri O F, Durojaiye M A, Adenike A (2015). Combined effects of repeated administration of Bretmont Wipeout (glyphosate) and Ultrazin (atrazine) on testosterone, oxidative stress and sperm quality of Wistar rats. Toxicology Mechanisms and Methods, 25, 70–80.
  • Agarwal A, Virk G, Ong C, du Plessis S S, (2014). Effect of oxidative stress on male reproduction. The World Journal of Men’s Health., 32, 1–17.
  • Akinlolu A A, Akinlola O B, Khobe P, Obasi K and Dada O (2014). Azathioprine and Methotrexate impaired the morphology and functions of the testes in adult wistar rats. Journal of Morphological Sciences, 31 (2), 75- 81.
  • Aldemir M, Okulu E, Kösemehmetoğlu K, Ener K, Topal F, Evirgen O, Avcı A. (2013). Evaluation of the protective effect of quercetin against cisplatin-induced renal and testis tissue damage and sperm parameters in rats. Andrologia, 46(10), 1089–1097.
  • Alhoshani A R, Hafez M M, Husain S, Al-sheikh Abdel Malek, Alotaibi M R, Al Rejaie S S et al. (2017). Protective effect of rutin supplementation against cisplatin-induced Nephrotoxicity in rats. BMC Nephrology, 18(1),194.
  • Al-Roujeaie A S, Abuohashish H M, Ahmed M M, Alkhamees O A (2016). Effect of rutin on diabetic-induced erectile dysfunction: Possible involvement of testicular biomarkers in male rats. Andrologia, 49(8), 1-9.
  • American Botancial Council (2005). Integrative Medical Communication Monographs Austin (Internet). http://www.abc@herbalgram.com.
  • Annapurna A, Ansari M A, Manjunath PM (2013). Partial role of multiple pathways in infarct size limiting effect of quercetin and Rutin against cerebral ischemia-reperfusion injury in rats. European Review for Medical and Pharmacological Sciences, 17(4), 491–500.
  • Araújo J R, Gonçalves P, Martel F. (2011). Chemopreventive effect of dietary polyphenols in colorectal cancer cell lines. Nutrition Research, 31(2), 77–87.
  • Ashraf J, Nagma J S, Nagma M, Mirani N and Rub A. (2012). Protective effect of rutin against carbon tetrachloride-induced hepatotoxicity in mice. International Journal of Drug Development & Research, 4(2), 352-357.
  • Bai L, Li A, Gong C, Ning X, Wang Z. (2020). Protective effect of rutin against bleomycin induced lung fibrosis: Involvement of TGFβ1/α-SMA/Col I and III pathway. BioFactors,1-8. doi: 10.1002/biof.1629.
  • Beigi Boroujeni M B, Shahrokhi S S, Birjandi M, Abbaszadeh A, Beyranvand F, Hamoleh S, Gholami M (2017). Effects of pomegranate peel extract on histopathology, testosterone levels and sperm of testicular torsion–detorsion induced in adult Wistar rats. Journal of Complementary and Integrative Medicine, 14(4),1-4
  • Benavente-García O, Castillo J, Marin F R, Ortuño A, Del Río J A (1997). Uses and properties of citrus flavonoids. Journal of agricultural and food chemistry, 45(12), 4505-4515.
  • British Medical Association and Royal Pharmaceutical Society. (2013). British National Formulary. United Kingdom: Pharmaceutical Press. P. 583-585.
  • Ceccatelli S, Tamm C, Zhang Q, Chen M, (2007). Mechanisms and modulation of neural cell damage induced by oxidative stress. Physiology & Behavior, 92(1-2), 87-92.
  • Chauhan K, Kaur G, Kaur S (2018). Activity of rutin, a potent flavonoid against SSG-sensitive and -resistant Leishmania donovani parasites in experimental leishmaniasis. International Immunopharmacology, 64,372–385.
  • Chen H, Miao Q, Geng M, Liu J, Hu Y, Tian L, Pan J, Yang Y. (2013). Anti-tumor effect of rutin on human neuroblastoma cell lines through inducing G2/M cell cycle arrest and promoting apoptosis. Scientific World Journal, 2013(20), 1-8
  • Chow J M, Shen S C, Huan S K, Lin H Y, Chen Y C (2005). Quercetin, but not rutin and quercitrin, prevention of H2O2-induced apoptosis via anti-oxidant activity and heme oxygenase 1 gene expression in macrophages. Biochemical pharmacology, 69(12), 1839-1851.
  • Das U B, Mallick M, Debnath J M, Ghosh D. (2002). Protective effect of ascorbic acid on cyclophosphamide-induced testicular gametogenic and androgenic disorders in male rats. Asian journal of andrology, 4(3), 201-208.
  • Duffield T. (2000). Subclinical ketosis in lactating dairy cattle. Veterinary Clinics of North America: Food animal practice, 16(2), 231-253.
  • El Sheikha A F (2015). Rumex nervosus: an overview. International Journal of Innovative Horticulture, 4(2),87–95.
  • Elelaimy I A, Elfiky S A, Hassan A M, Ibrahim H M, Elsayad R I (2012). Genotoxicity of anticancer drug Azathioprine (Imuran): role of Omega-3 (ω-3) oil as protective agent. Journal of Applied Pharmaceutical Science, 2 (4), 14-23.
  • Elfiky S A, Elelaimy I A, Hassan A M, Ibrahim H M, Elsayad R I (2012). Protective effect of pumpkin seed oil against genotoxicity induced by azathioprine. The Journal of Basic & Applied Zoology, 65, 289–298.
  • Elsawy H, Badr G M, Sedky A, Abdallah B M, Alzahrani A M, Abdel-Moneim A M, (2019). Rutin ameliorates carbon tetrachloride (CCl4)-induced hepatorenal toxicity and hypogonadism in male rats. Peer J, 7,e7011.
  • Ezer N, and Robaire B (2002). Androgenic regulation of the structure and functions of the epididymis. In: The Epididymis From Molecules to Clinical Practice. Robaire, B. and Hinton, B.T. (eds). P. 297-316.
  • Ganeshpurkar A, Saluja A K, (2017). The Pharmacological Potential of Rutin. Saudi Pharmaceutical Journal. 25(2), 149–16
  • Ghiasi M, Azadnia A, Arabieh M, Zahedi M (2012). Protective effect of Rutin (vitamin p) against heme oxidation: A quantum mechanical approach. Computational and Theoretical Chemistry, 996, 28–36.
  • Gholami M, Saki G, Hemadi M, Khodadadi A, Mohammadi-asl J (2014). Melatonin improves spermatogonial stem cells transplantation efficiency in azoospermic mice. Iranian journal of basic medical sciences, 17(2), 93-99.
  • Gul A, Kunwar B, Mazhar M, Faizi S, Ahmed D, Raza Shah M, Simjee S U (2018). Rutin and rutin-conjugated gold nanoparticles ameliorate collagen-induced arthritis in rats through inhibition of NF-κB and iNOS activation. International Immunopharmacology, 59, 310–317.
  • Hamza R Z, El-Shenawy N S, and Ismail H A (2015). Protective effects of blackberry and quercetin on sodium fluoride-induced oxidative stress and histological changes in the hepatic, renal, testis and brain tissue of male rat. Journal of Basic and Clinical Physiology and Pharmacology, 26(3),237- 251.
  • Hamzeh, M., Hosseinimehr, S.J., Karimpour, A., Mohammadi, H.R., Khalatbary, A.R., & Talebpour Amiri, F. (2019).Cerium oxide nanoparticles protect cyclophosphamide-induced testicular toxicity in mice. International Journal of Preventive Medicine, 10(1),5-14.
  • Ismail H, Maksimović J D, Maksimović V, Shabala L, Živanović B D, Tian Y, Shabala S. (2016). Rutin, a flavonoid with antioxidant activity, improves plant salinity tolerance by regulating K+ retention and Na+ exclusion from leaf mesophyll in quinoa and broad beans. Functional Plant Biology, 43(1), 75-86.
  • Jahnukainen K, Ehmcke J, Hou M, Schlatt S (2011). Testicular function and fertility preservation in male cancer patients. Best practice & research Clinical endocrinology & metabolism, 25(2), 287-302.
  • Kamel K M, Abd El-Raouf O M, Metwally S A, Abd El-Latif H A, El-sayed M E, (2014). Hesperidin and Rutin, Antioxidant Citrus Flavonoids, Attenuate Cisplatin-Induced Nephrotoxicity in Rats. Journal of Biochemical and Molecular Toxicology, 28(7), 312–319.
  • Khaki A, (2011). Anti-oxidative effects of citro flavonoids on spermatogenesis in rat. African Journal of Pharmacy and Pharmacology, 5(6), 721–725.
  • Khaksary M M, Gholami M R, Najafzadeh V H, Zendedel A, Doostizadeh M. (2016). Protective effect of quercetin on skeletal and neural tube teratogenicity induced by cyclophosphamide in rat fetuses. In Veterinary Research Forum, 7 (2), 133-138.
  • Liang W, Zhang D, Kang J, Meng X, Yang J, Yang L, Xue N, et al. (2018). Protective effects of rutin on liver injury in type 2 diabetic db/db mice. Biomedicine & Pharmacotherapy, 107, 721–728.
  • Lin J-P, Yang J-S, Lu C-C, Wu S-Y, Lan S-H, Liao S-S, Chung J-G (2007). Rutin inhibits WEHI‐3 leukemia cells in Balb/C mice in vivo. The FASEB Journal, 21 (6), A1190-A119.
  • Martin L J, Touaibia M. (2020). Improvement of Testicular Steroidogenesis Using Flavonoids and Isoflavonoids for Prevention of Late-Onset Male Hypogonadism. Antioxidants., 9(3), 237.
  • Mirani N, Ashraf N J, Siddique J, Rub A. (2012). Protective effect of rutin against cadmium induced hepatotoxicity in Swiss albino mice. Journal of Pharmacology and Toxicology, 7, 150-157.
  • Moazamian R, Polhemus A, Connaughton H, Fraser B, Whiting S, Gharagozloo P, Aitken R J (2015). Oxidative stress and human spermatozoa: diagnostic and functional significance of aldehydes generated as a result of lipid peroxidation. Molecular Human Reproduction, 21(6), 502–515.
  • Mohammad F E, Hasan W A, Mohamed E G (2017). Natural antioxidant flavonoids in formalin-induced mice paw inflammation; inhibition of mitochondrial sorbitol dehydrogenase activity. Journal of Biochemical and Molecular Toxicology, 31(7), 1-8.
  • Mohammad S A, Ramadan B K, Schaalan M F (2018). Mitigation of Azathioprine-induced Testicular Atrophy by Taurine; An Impact on Inflammation, Oxidative Perturbations and Apoptosis. Canadian Journal of Physiology and Pharmacology, 96(3), 1–43.
  • Morgan J A, Lynch J, Panetta J C, Wang Y, Frase S, Bao J, Schuetz J D (2015). Apoptosome activation, an important molecular instigator in 6-mercaptopurine induced Leydig cell death. Scientific Reports, 5(1),1-11.
  • Park H J, Choi Y J, Lee J H, Nam M J (2017). Naringenin causes ASK1-induced apoptosis via reactive oxygen species in human pancreatic cancer cells. Food and Chemical Toxicology, 99, 1–8.
  • Pires V C, Gollücke A P, Ribeiro D A, Lungato L, D’Almeida V, Aguiar O (2013). Grape juice concentrate protects reproductive parameters of male rats against cadmium-induced damage: A chronic assay. British Journal of Nutrition, 110, 2020–2029.
  • Qasim M and Al-Mayali H K (2019). Investigate the relation between Baicalin effect and gene expression of LH, FSH, Testosterone in male rats treated with Gemcitabine drug. Research Journal of Pharmacy and Technology,12 (9),4135-4141.
  • Ramadan B K, Schaalan M F, Mahmoud E S (2018). Protective Effect of Taurine on Thiopurine-Induced Testicular Atrophy in Male Albino Rats. Journal of Steroids & Hormonal Science, 9(1),192.
  • Salem E A, Salem N A, Hellstrom W J (2016). Therapeutic effect of ozone and rutin on adriamycin-induced testicular toxicity in an experimental rat model. Andrologia, 49(1),e12603.
  • Salem E A, Salem N A, Hellstrom W J (2016). Therapeutic effect of ozone and rutin on adriamycin-induced testicular toxicity in an experimental rat model. Andrologia, 49(1),1-7.
  • Seid M A, Aydagnehum S G (2013). Medicinal plants biodiversity and local healthcare management system in Chencha district; Gamo Gofa, Ethiopia. Journal of Pharmacognosy and Phytochemistry, 2(1),284–293.
  • Silva C A, Hallak J, Pasqualotto F F, Barba M F, Saito M I, Kiss M H (2002). Gonadal function in male adolescents and young males with juvenile onset systemic lupus erythematosus. The Journal of Rheumatology, 29(9), 2000-2005.
  • Stumpp T, Freymüller E, Miraglia S M, (2006). Sertoli cell function in albino rats treated with etoposide during prepubertal phase. Histochemistry and cell biology, 126(3), 353-361
  • Tripathi K D, (2003).Essentials of Medical Pharmacology. 5th ed. India : Jaypee Brothers Medical Publishers, p. 769-774.
  • Tuhin RH, Begum MM, Rahman MS, Karim R, Begum T, Ahmed SU, Mostofa R, Hossain A, Abdel-Daim M, Begum R. (2017).Wound healing effect of Euphorbia hirta linn. (Euphorbiaceae) in alloxan induced diabetic rats. BMC Complementary and Alternative Medicine,17(1),423.
  • Wang Y D, Zhang Y, Sun B, Leng X W, Li Y J, Ren L Q (2017). Cardioprotective effects of rutin in rats exposed to pirarubicin toxicity. Journal of Asian Natural Products Research, 20(4), 361–373.
  • Xu D, Wu L, Yang L, Liu D, Chen H, Geng G, Li Q (2020). Rutin protects boar sperm from cryodamage via enhancing the antioxidative defense. Animal Science Journal, 91(1),1-10.
  • Yent S S C, Jaffe R B, and Barbieri R L (1999). Reproductive Endocrinology, Physiology, Pathophysiology and Clinical management. 4th ed.
  • Yeung A W K, Tzvetkov N T, El-Tawil O S, Bungǎu S G, Abdel-Daim M M, Atanasov A G (2019). Antioxidants: Scientific Literature Landscape Analysis. Oxidative Medicine and Cellular Longevity, 2019,1–11.
  • Zendedel A, Gharibi Z, Anbari K, Abbaszadeh A, Khorramabadi R M, Soleymaninejad M, Gholami M (2017). Selenium ameliorate peripheral nerve ischemic-reperfusion injury via decreased TNF-α. Biological trace element research, 176(2), 328-337.

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