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RESEARCH ARTICLE

Protective effects of polydatin on experimental testicular torsion and detorsion injury in rats

Huilian Qiao A , He Ma A , Wanjun Cao A , Hao Chen B , Jinhua Wei A and Zhen Li A C
+ Author Affiliations
- Author Affiliations

A Department of Histology and Embryology, The Fourth Military Medical University, Xi’an, Shaan Xi Province, 710032, PR China.

B Department of Cardiovascular Center, The 309th Hospital of Chinese PLA, Beijing, 100193, PR China.

C Corresponding author. Email: lizhenhe@fmmu.edu.cn

Reproduction, Fertility and Development 29(12) 2367-2375 https://doi.org/10.1071/RD17046
Submitted: 7 February 2017  Accepted: 20 March 2017   Published: 26 April 2017

Abstract

Oxidative stress plays a critical role in the process of testicular torsion and detorsion (T/D). The purpose of the present study was to investigate the protective effect of polydatin (PD) on testicular T/D injury. Rats were randomly divided into three groups, a sham group, a group subjected to 2 h torsion followed by 24 h detorsion and a group subjected to T/D and injected i.p. with 20 mg kg−1 PD 30 min before detorsion. Unilateral orchiectomy was performed after 24 h of reperfusion. Half the testes were prepared for histological examination by haematoxylin–eosin staining and the terminal deoxyribonucleotidyl transferase-mediated dUTP–digoxigenin nick end-labelling (TUNEL) technique. In the remaining tissues, levels of malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) were determined, as was the expression of several apoptosis-related proteins. Compared with the T/D group, PD pretreatment significantly ameliorated the morphological damage, lowered the Cosentino histological score and increased the mean number of germ cell layers and Johnsen’s testicular biopsy score. In addition, PD treatment markedly decreased MDA levels and upregulated CAT, GPx and SOD activity. Furthermore, PD decreased T/D-induced germ cell-specific apoptosis, attenuated the activation of caspase-3, caspase-8, caspase-9 and poly(ADP-ribose) polymerase and increased the Bcl-2/Bax ratio. The findings indicate that PD has a protective effect against testicular T/D injuries, especially at the histological, antioxidative stress and antiapoptotic levels.

Additional keywords: ischaemia–reperfusion, oxidative stress, apoptosis.


References

Agarwal, A., Mahfouz, R. Z., Sharma, R. K., Sarkar, O., Mangrola, D., and Mathur, P. P. (2009). Potential biological role of poly(ADP-ribose) polymerase (PARP) in male gametes. Reprod. Biol. Endocrinol. 7, 143.
Potential biological role of poly(ADP-ribose) polymerase (PARP) in male gametes.Crossref | GoogleScholarGoogle Scholar |

Aitken, R. J., and Baker, M. A. (2004). Oxidative stress and male reproductive biology. Reprod. Fertil. Dev. 16, 581–588.
Oxidative stress and male reproductive biology.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXlvVensLo%3D&md5=9b0529155b3ac8d55c8c28ed1b85e1a5CAS |

Akgür, F. M., Kilinç, K., and Aktuĝ, T. (1993). Reperfusion injury after detorsion of unilateral testicular torsion. Urol. Res. 21, 395–399.
Reperfusion injury after detorsion of unilateral testicular torsion.Crossref | GoogleScholarGoogle Scholar |

Allanore, Y., Borderie, D., Périanin, A., Lemaréchal, H., Ekindjian, O. G., and Kahan, A. (2005). Nifedipine protects against overproduction of superoxide anion by monocytes from patients with systemic sclerosis. Arthritis Res. Ther. 7, R93–R100.
Nifedipine protects against overproduction of superoxide anion by monocytes from patients with systemic sclerosis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXkvFSjsQ%3D%3D&md5=1846c06d423d70702f15a9673b23ec22CAS |

Ban, S. H., Kwon, Y. R., Pandit, S., Lee, Y. S., Yi, H. K., and Jeon, J. G. (2010). Effects of a bio-assay guided fraction from Polygonum cuspidatum root on the viability, acid production and glucosyltranferase of mutans streptococci. Fitoterapia 81, 30–34.
Effects of a bio-assay guided fraction from Polygonum cuspidatum root on the viability, acid production and glucosyltranferase of mutans streptococci.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhsVGmt7%2FL&md5=efb1a6b3160f52a44ef3f651ee7d501eCAS |

Cao, L., Quan, X. B., Zeng, W. J., Yang, X. O., and Wang, M. J. (2016). Mechanism of hepatocyte apoptosis. J. Cell Death 9, 19–29.

Cattolica, E. V., Karol, J. B., Rankin, K. N., and Klein, R. S. (1982). High testicular salvage rate in torsion of the spermatic cord. J. Urol. 128, 66–68.
| 1:STN:280:DyaL383mvFaltg%3D%3D&md5=8ac6f428598505a6bc37afee095caa1dCAS |

Cayli, S., Ocakli, S., Senel, U., Karaca, Z., Erdemir, F., and Delibasi, T. (2016). Role of an endothelin type A receptor antagonist in regulating torsion-induced testicular apoptosis in rats. Histol. Histopathol. 31, 585–594.
| 1:CAS:528:DC%2BC2sXivV2htrc%3D&md5=3016c182864feff97a2e93103237dcd4CAS |

Chi, K. K., Zhang, W. H., Wang, G. C., Chen, Z., He, W., Wang, S. G., Cui, Y., Lu, P., Wang, X. J., and Chen, H. (2017). Comparison of intraperitoneal and intraepididymal quercetin for the prevention of testicular torsion/detorsion-induced injury. Urology 99, 106–111.
Comparison of intraperitoneal and intraepididymal quercetin for the prevention of testicular torsion/detorsion-induced injury.Crossref | GoogleScholarGoogle Scholar |

Clark, R. E., Christlieb, I. Y., Vanderwonde, J. C., and Henry, P. D. (1985). Use of nifedipine to decrease ischemic–reperfusion injury in the surgical setting. Am. J. Cardiol. 55, B125–B138.
Use of nifedipine to decrease ischemic–reperfusion injury in the surgical setting.Crossref | GoogleScholarGoogle Scholar |

Cosentino, M. J., Nishida, M., Rabinowitz, R., and Cockett, A. T. (1986). Histopathology of prepubertal rat testes subjected to various durations of spermatic cord torsion. J. Androl. 7, 23–31.
Histopathology of prepubertal rat testes subjected to various durations of spermatic cord torsion.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL287htFegsQ%3D%3D&md5=76dc17a612a616767084310a664dab13CAS |

Culmsee, C., and Landshamer, S. (2006). Molecular insights into mechanisms of the cell death program: role in the progression of neurodegenerative disorders. Curr. Alzheimer Res. 3, 269–283.
Molecular insights into mechanisms of the cell death program: role in the progression of neurodegenerative disorders.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xos1Kjsro%3D&md5=882682bf461d4fd16975efbdaa2b02ecCAS |

Dandona, P., Qutob, T., Hamouda, W., Bakri, F., Aljada, A., and Kumbkarni, Y. (1999). Heparin inhibits reactive oxygen species generation by polymorphonuclear and mononuclear leucocytes. Thromb. Res. 96, 437–443.
Heparin inhibits reactive oxygen species generation by polymorphonuclear and mononuclear leucocytes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXotVKns70%3D&md5=d28ebd47e062e45f0d6f86d62fe02c3cCAS |

Erbel, R., Pop, T., Meinertz, T., Olshausen, K. V., Treese, N., Henrichs, K. J., Schuster, C. J., Rupprecht, H. J., Schlürmann, W., and Meyer, J. (1988). Combination of calcium channel blocker and thrombolytic therapy in acute myocardial infarction. Am. Heart J. 115, 529–538.
Combination of calcium channel blocker and thrombolytic therapy in acute myocardial infarction.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL1c7kslOlsA%3D%3D&md5=e31f14bc13e1eccbea091a29321339faCAS |

Filho, D. W., Torres, M. A., Bordin, A. L., Crezcynski-Pasa, T. B., and Boveris, A. (2004). Spermatic cord torsion, reactive oxygen and nitrogen species and ischemia–reperfusion injury. Mol. Aspects Med. 25, 199–210.
Spermatic cord torsion, reactive oxygen and nitrogen species and ischemia–reperfusion injury.Crossref | GoogleScholarGoogle Scholar |

Gao, Y., Chen, T., Lei, X., Li, Y., Dai, X., Cao, Y., Ding, Q., Lei, X., Li, T., and Lin, X. (2016). Neuroprotective effects of polydatin against mitochondrial-dependent apoptosis in the rat cerebral cortex following ischemia/reperfusion injury. Mol. Med. Rep. 14, 5481–5488.
Neuroprotective effects of polydatin against mitochondrial-dependent apoptosis in the rat cerebral cortex following ischemia/reperfusion injury.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2sXitl2ksLk%3D&md5=413233b65beb5865a2dad42d786bdfb2CAS |

Garber, J. C., Barbee, R. W., Bielitzki, J. T., Clayton, L. A., Donovan, J. C., Hendriksen, C. F. M., Kohn, D. F., Lipman, N. S., Locke, P. A., Melcher, J., Quimby, F. W., Turner, P. V., Wood, G. A., and Würbel, H. (2011). ‘Guide for the Care and Use of Laboratory Animals.’ 8th edn. (National Academies Press: Washington, DC.)

Gezici, A., Ozturk, H., Buyukbayram, H., Ozturk, H., and Okur, H. (2006). Effects of gabexate mesilate on ischemia–reperfusion-induced testicular injury in rats. Pediatr. Surg. Int. 22, 435–441.
Effects of gabexate mesilate on ischemia–reperfusion-induced testicular injury in rats.Crossref | GoogleScholarGoogle Scholar |

Góth, L. (1991). A simple method for determination of serum catalase activity and revision of reference range. Clin. Chim. Acta 196, 143–151.
A simple method for determination of serum catalase activity and revision of reference range.Crossref | GoogleScholarGoogle Scholar |

Gozen, A., Demiryurek, S., Taskin, A., Ciralik, H., Bilinc, H., Kara, S., Aydin, A., Aksoy, N., and Ceylan, H. (2013). Protective activity of ischemic preconditioning on rat testicular ischemia: effects of Y-27632 and 5-hydroxydecanoic acid. J. Pediatr. Surg. 48, 1565–1572.
Protective activity of ischemic preconditioning on rat testicular ischemia: effects of Y-27632 and 5-hydroxydecanoic acid.Crossref | GoogleScholarGoogle Scholar |

Ince, S., Avdatek, F., Demirel, H. H., Arslan-Acaroz, D., Goksel, E., and Kucukkurt, I. (2016). Ameliorative effect of polydatin on oxidative stress-mediated testicular damage by chronic arsenic exposure in rats. Andrologia 48, 518–524.
Ameliorative effect of polydatin on oxidative stress-mediated testicular damage by chronic arsenic exposure in rats.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC28XntlSrs70%3D&md5=f383a84f75a269b486893b717e9aad05CAS |

Ji, H., Zhang, X., Du, Y., Liu, H., Li, S., and Li, L. (2012). Polydatin modulates inflammation by decreasing NF-kappaB activation and oxidative stress by increasing Gli1, Ptch1, SOD1 expression and ameliorates blood–brain barrier permeability for its neuroprotective effect in pMCAO rat brain. Brain Res. Bull. 87, 50–59.
Polydatin modulates inflammation by decreasing NF-kappaB activation and oxidative stress by increasing Gli1, Ptch1, SOD1 expression and ameliorates blood–brain barrier permeability for its neuroprotective effect in pMCAO rat brain.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhs12gsrrM&md5=7a3ba246186180f4cab815868877a7baCAS |

Johnsen, S. G. (1970). Testicular biopsy score count – a method for registration of spermatogenesis in human testes: normal values and results in 335 hypogonadal males. Hormones 1, 2–25.
| 1:STN:280:DyaE3s7kslKitw%3D%3D&md5=0fe0b3b460cc7b383890c1f20f9c7c5dCAS |

Kabay, S., Ozden, H., Guven, G., Burukoglu, D., Ustuner, M. C., Topal, F., Gunes, H. V., Ustuner, D., and Ozbayer, C. (2014). Protective effects of the nuclear factor kappa B inhibitor pyrrolidine dithiocarbamate on experimental testicular torsion and detorsion injury. Korean J. Physiol. Pharmacol. 18, 321–326.
Protective effects of the nuclear factor kappa B inhibitor pyrrolidine dithiocarbamate on experimental testicular torsion and detorsion injury.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhsl2mtrrP&md5=dd1ed70c186bdec1923e4208c087ea6aCAS |

Kanter, M. (2010). Protective effects of melatonin on testicular torsion/detorsion-induced ischemia–reperfusion injury in rats. Exp. Mol. Pathol. 89, 314–320.
Protective effects of melatonin on testicular torsion/detorsion-induced ischemia–reperfusion injury in rats.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhsVans7rF&md5=d81f8b4768674d62ad0c16421c72f213CAS |

Kimura, M., Itoh, N., Takagi, S., Sasao, T., Takahashi, A., Masumori, N., and Tsukamoto, T. (2003). Balance of apoptosis and proliferation of germ cells related to spermatogenesis in aged men. J. Androl. 24, 185–191.
Balance of apoptosis and proliferation of germ cells related to spermatogenesis in aged men.Crossref | GoogleScholarGoogle Scholar |

Krarup, T. (1978). The testes after torsion. Br. J. Urol. 50, 43–46.
The testes after torsion.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaE1c7isVOisg%3D%3D&md5=6d21ddd37fdab1c067629f4853f2e1abCAS |

Li, T., Cai, S., Zeng, Z., Zhang, J., Gao, Y., Wang, X., and Chen, Z. (2014). Protective effect of polydatin against burn-induced lung injury in rats. Respir. Care 59, 1412–1421.
Protective effect of polydatin against burn-induced lung injury in rats.Crossref | GoogleScholarGoogle Scholar |

Liu, L. T., Guo, G., Wu, M., and Zhang, W. G. (2012). The progress of the research on cardio-vascular effects and acting mechanism of polydatin. Chin. J. Integr. Med. 18, 714–719.
The progress of the research on cardio-vascular effects and acting mechanism of polydatin.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xht12msbfL&md5=bb8a1c8848db5d423fdbab07b32c23a4CAS |

Liu, H. B., Meng, Q. H., Huang, C., Wang, J. B., and Liu, X. W. (2015). Nephroprotective effects of polydatin against ischemia/reperfusion injury: a role for the PI3K/Akt signal pathway. Oxid. Med. Cell. Longev. 2015, 362158.
Nephroprotective effects of polydatin against ischemia/reperfusion injury: a role for the PI3K/Akt signal pathway.Crossref | GoogleScholarGoogle Scholar |

Lo Monte, G., Soave, I., and Marci, R. (2013). Administration of micronized palmitoylethanolamide (PEA)-transpolydatin in the treatment of chronic pelvic pain in women affected by endometriosis: preliminary results. Minerva Ginecol. 65, 453–463.
| 1:STN:280:DC%2BC2c7lslWqug%3D%3D&md5=147c33cfbc848b63864f64605e08a647CAS |

Lysiak, J. J., Turner, S. D., and Turner, T. T. (2000). Molecular pathway of germ cell apoptosis following ischemia/reperfusion of the rat testis. Biol. Reprod. 63, 1465–1472.
Molecular pathway of germ cell apoptosis following ischemia/reperfusion of the rat testis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXnslCktb4%3D&md5=91a8d9af0b2c1ffb792299e28c47868dCAS |

Mak, I. T., and Weglicki, W. B. (1990). Comparative antioxidant activities of propranolol, nifedipine, verapamil, and diltiazem against sarcolemmal membrane lipid peroxidation. Circ. Res. 66, 1449–1452.
Comparative antioxidant activities of propranolol, nifedipine, verapamil, and diltiazem against sarcolemmal membrane lipid peroxidation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3cXktFOltbk%3D&md5=581e439069ef4f6a2b71eb4208b41215CAS |

McCord, J. M. (1985). Oxygen-derived free radicals in postischemic tissue injury. N. Engl. J. Med. 312, 159–163.
Oxygen-derived free radicals in postischemic tissue injury.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL2MXptlOmtA%3D%3D&md5=530fa8ffa94f275d1fe8a1a5ba379eaaCAS |

Means, L., Benken, S. T., and Tesoro, E. P. (2016). Safety of immediate-release nifedipine. J. Cardiovasc. Pharmacol. 68, 395–399.
Safety of immediate-release nifedipine.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC28XhvVSnsLrO&md5=39547b150b1b893f7cdde12576912bdaCAS |

Meštrović, J., Drmić-Hofman, I., Pogorelić, Z., Vilović, K., Šupe-Domić, D., Šešelja-Perišin, A., and Capkun, V. (2014). Beneficial effect of nifedipine on testicular torsion–detorsion injury in rats. Urology 84, 1194–1198.
Beneficial effect of nifedipine on testicular torsion–detorsion injury in rats.Crossref | GoogleScholarGoogle Scholar |

Meštrović, J., Pogorelić, Z., Drmić-Hofman, I., Vilović, K., Todorić, D., and Popović, M. (2017). Protective effect of urapidil on testicular torsion–detorsion injury in rats. Surg. Today 47, 393–398.
Protective effect of urapidil on testicular torsion–detorsion injury in rats.Crossref | GoogleScholarGoogle Scholar |

Nowak, G. (2009). Heparin-induced thrombocytopenia (HIT II) – a drug-associated autoimmune disease. Thromb. Haemost. 102, 887–891.
| 1:CAS:528:DC%2BD1MXhsFajtrzP&md5=fe7d4c9ab053ea2128e11435b05a80c6CAS |

Ohkawa, H., Ohishi, N., and Yagi, K. (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem. 95, 351–358.
Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE1MXksFaisbk%3D&md5=a58c04dcf7264317a4ad5482e83c4e93CAS |

Ozturk, H., Ozturk, H., Terzi, E. H., Bugdayci, G., and Duran, A. (2014). Interleukin 10 reduces testicular damage in experimental testicular ischemia/reperfusion injury. Urology 83, 508.e1–508.e6.
Interleukin 10 reduces testicular damage in experimental testicular ischemia/reperfusion injury.Crossref | GoogleScholarGoogle Scholar |

Pogorelić, Z., Mrklić, I., and Jurić, I. (2013). Do not forget to include testicular torsion in differential diagnosis of lower acute abdominal pain in young males. J. Pediatr. Urol. 9, 1161–1165.
Do not forget to include testicular torsion in differential diagnosis of lower acute abdominal pain in young males.Crossref | GoogleScholarGoogle Scholar |

Pogorelić, Z., Mustapić, K., Jukić, M., Todorić, J., Mrklić, I., Mešštrović, J., Jurić, I., and Furlan, D. (2016). Management of acute scrotum in children: a 25-year single center experience on 558 pediatric patients. Can. J. Urol. 23, 8594–8601.

Poli, G., Cutrin, J. C., and Biasi, F. (1998). Lipid peroxidation in the reperfusion injury of the liver. Free Radic. Res. 28, 547–551.
Lipid peroxidation in the reperfusion injury of the liver.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXlvFegt7Y%3D&md5=899ed93cef0bf43466bd9c024334a4aeCAS |

Qiao, H., Chen, H., Dong, Y., Ma, H., Zhao, G., Tang, F., and Li, Z. (2016). Polydatin attenuates H2O2-induced oxidative stress via PKC pathway. Oxid. Med. Cell. Longev. 2016, 5139458.
Polydatin attenuates H2O2-induced oxidative stress via PKC pathway.Crossref | GoogleScholarGoogle Scholar |

Saba, M., Morales, C. R., De Lamirande, E., and Gagnon, C. (1997). Morphological and biochemical changes following acute unilateral testicular torsion in prepubertal rats. J. Urol. 157, 1149–1154.
Morphological and biochemical changes following acute unilateral testicular torsion in prepubertal rats.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXhsVKgtb4%3D&md5=68211162ef5573fd45e08c07c0199de6CAS |

Taati, M., Moghadasi, M., Dezfoulian, O., Asadian, P., and Zendehdel, M. (2015). Effects of ghrelin on germ cell apoptosis and proinflammatory cytokines production in ischemia–reperfusion of the rat testis. Iran. J. Reprod. Med. 13, 85–92.

Turner, T. T., and Brown, K. J. (1993). Spermatic cord torsion: loss of spermatogenesis despite return of blood flow. Biol. Reprod. 49, 401–407.
Spermatic cord torsion: loss of spermatogenesis despite return of blood flow.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK3szosFemsQ%3D%3D&md5=4ebd4531eae3c8ec58ff43a0a0c45226CAS |

Turner, T. T., Tung, K. S., Tomomasa, H., and Wilson, L. W. (1997). Acute testicular ischemia results in germ cell-specific apoptosis in the rat. Biol. Reprod. 57, 1267–1274.
Acute testicular ischemia results in germ cell-specific apoptosis in the rat.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXnvVWgsL4%3D&md5=4a85739778d8799d91e26c1282f5cdb1CAS |

Uchiyama, M., and Mihara, M. (1978). Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal. Biochem. 86, 271–278.
Determination of malonaldehyde precursor in tissues by thiobarbituric acid test.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE1cXhvVGlsr4%3D&md5=af49a6b6788269dd600a29df8ebedde5CAS |

Uguralp, S., Bay, K. A., Mizrak, B., Kaymaz, F., Kiziltay, A., and Hasirci, N. (2004). The effect of sustained and local administration of epidermal growth factor on improving bilateral testicular tissue after torsion. Urol. Res. 32, 323–331.
The effect of sustained and local administration of epidermal growth factor on improving bilateral testicular tissue after torsion.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXovVCmsr0%3D&md5=bb72ec2f1626b1f487d27e7ea6e99288CAS |

Wei, S. M., Yan, Z. Z., and Zhou, J. (2011). Protective effect of rutin on testicular ischemia–reperfusion injury. J. Pediatr. Surg. 46, 1419–1424.
Protective effect of rutin on testicular ischemia–reperfusion injury.Crossref | GoogleScholarGoogle Scholar |

Welsh, R. C., Sauriol, L., Zhang, Z., Kolm, P., Weintraub, W. S., and Theroux, P. (2009). Cost-effectiveness of enoxaparin compared with unfractionated heparin in ST elevation myocardial infarction patients undergoing pharmacological reperfusion: a Canadian analysis of the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis in Myocardial Infarction (ExTRACT-TIMI) 25 trial. Can. J. Cardiol. 25, e399–e405.
Cost-effectiveness of enoxaparin compared with unfractionated heparin in ST elevation myocardial infarction patients undergoing pharmacological reperfusion: a Canadian analysis of the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis in Myocardial Infarction (ExTRACT-TIMI) 25 trial.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXktlWnsw%3D%3D&md5=b4a3c6c9a013fe33b474214a93594aa8CAS |

Xu, L. Q., Xie, Y. L., Gui, S. H., Zhang, X., Mo, Z. Z., Sun, C. Y., Li, C. L., Luo, D. D., Zhang, Z. B., Su, Z. R., and Xie, J. H. (2016). Polydatin attenuates d-galactose-induced liver and brain damage through its anti-oxidative, anti-inflammatory and anti-apoptotic effects in mice. Food Funct. 7, 4545–4555.
Polydatin attenuates d-galactose-induced liver and brain damage through its anti-oxidative, anti-inflammatory and anti-apoptotic effects in mice.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC28XhsFOrsb3E&md5=7a80415bb4621be5537cbf1a54bcbb12CAS |

Yuluğ, E., Türedi, S., Karagüzel, E., Kutlu, Ö., Menteşe, A., and Alver, A. (2014). The short term effects of resveratrol on ischemia–reperfusion injury in rat testis. J. Pediatr. Surg. 49, 484–489.
The short term effects of resveratrol on ischemia–reperfusion injury in rat testis.Crossref | GoogleScholarGoogle Scholar |

Zhang, L. P., Ma, H. J., Bu, H. M., Wang, M. L., Li, Q., Qi, Z., and Zhang, Y. (2009). Polydatin attenuates ischemia/reperfusion-induced apoptosis in myocardium of the rat. Sheng Li Xue Bao 61, 367–372.
| 1:CAS:528:DC%2BC3cXmsFKjsA%3D%3D&md5=806f86eb84039eda07816b88f258e918CAS |

Zhang, Y., Lv, Y., Liu, Y. J., Yang, C., Hu, H. J., Meng, X. E., Li, M. X., and Pan, S. Y. (2013). Hyperbaric oxygen therapy in rats attenuates ischemia–reperfusion testicular injury through blockade of oxidative stress, suppression of inflammation, and reduction of nitric oxide formation. Urology 82, 489.e9–489.e15.
Hyperbaric oxygen therapy in rats attenuates ischemia–reperfusion testicular injury through blockade of oxidative stress, suppression of inflammation, and reduction of nitric oxide formation.Crossref | GoogleScholarGoogle Scholar |