Skip to content
2000
image of Protective Effects of Chitosan-Loaded Pomegranate Peel Extract Nanoparticles on Infertility in Diabetic Male Rats

Abstract

Background

Diabetes Mellitus (DM) is known to have an impact on the health of the male reproductive system. It is linked to low sperm quality, increased oxidative stress, and an increased generation of reactive oxygen species in the seminal fluid. Pomegranate extract has phenolic compounds and significant protective properties against oxidative stress, male sex hormone disruptions, and sperm abnormalities.

Objective

The current study aimed to evaluate the effectiveness of Pomegranate Peel Extract Nanoparticles (PPENPs) on male fertility in diabetic rats.

Methods

DM was induced in rats by intraperitoneal injection of streptozotocin (60 mg/kg). Twenty-four rats were divided into four groups, 6 rats in each group: control, DM, DM+empty NPs (60 mg/kg, orally), and DM+PPENPs (60 mg/kg, orally).

Results

Administration of PPENPs increased the levels of insulin, FSH, LH, testosterone, catalase, glutathione reduced, and semen fructose. PPENPs also improved sperm quality, as seen by improvements in sperm morphology, motility, count, and the ability of metabolically active spermatozoa to convert blue resazurin dye to pink resorufin. However, PPENPs decreased levels of glucose, malonaldehyde, nitric oxide, and sperm abnormalities. Also, histological investigation of the PPENPs showed improvement in testis tissue architecture and increased the diameter size of seminiferous tubules and germinative layer thickness.

Conclusion

Our investigation proved that the treatment of PPENPs has a protective effect on the reproductive system of male diabetic rats, improving fertility parameters, healthy sperm profiles, and the antioxidant system.

Loading

Article metrics loading...

/content/journals/ctmc/10.2174/0115680266308882240806175831
2024-08-22
2024-12-03
Loading full text...

Full text loading...

References

  1. Taitson P.F. Mourthé A. Rodrigues L.M.F. Treating male infertility. JBRA Assist. Reprod. 2022 17 6 351 352 35939554
    [Google Scholar]
  2. Sharma A. Minhas S. Dhillo W.S. Jayasena C.N. Male infertility due to testicular disorders. J. Clin. Endocrinol. Metab. 2021 106 2 e442 e459 10.1210/clinem/dgaa781 33295608
    [Google Scholar]
  3. Eisenberg M.L. Esteves S.C. Lamb D.J. Hotaling J.M. Giwercman A. Hwang K. Cheng Y.S. Male infertility. Nat. Rev. Dis. Primers 2023 9 1 49 10.1038/s41572‑023‑00459‑w 37709866
    [Google Scholar]
  4. Concepción-Zavaleta M. Paz Ibarra J.L. Ramos-Yataco A. Coronado-Arroyo J. Concepción-Urteaga L. Roseboom P.J. Williams C.A. Assessment of hormonal status in male infertility. An update. Diabetes Metab. Syndr. 2022 16 3 102447 10.1016/j.dsx.2022.102447 35272174
    [Google Scholar]
  5. Strasser M.O. Dupree J.M. Care delivery for male infertility. Urol. Clin. North Am. 2020 47 2 193 204 10.1016/j.ucl.2019.12.006 32272991
    [Google Scholar]
  6. Jiao S.Y. Yang Y.H. Chen S.R. Molecular genetics of infertility: loss-of-function mutations in humans and corresponding knockout/mutated mice. Hum. Reprod. Update 2021 27 1 154 189 10.1093/humupd/dmaa034 33118031
    [Google Scholar]
  7. Rama N. Lescay H. Raheem O. Male factor infertility. Obstet. Gynecol. Clin. North Am. 2023 50 4 763 777 10.1016/j.ogc.2023.08.001 37914493
    [Google Scholar]
  8. Murshidi M.M. Choy J.T. Eisenberg M.L. Male infertility and somatic health. Urol. Clin. North Am. 2020 47 2 211 217 10.1016/j.ucl.2019.12.008 32272993
    [Google Scholar]
  9. Reed J. Bain S. Kanamarlapudi V. A review of current trends with type 2 diabetes epidemiology, aetiology, pathogenesis, treatments and future perspectives. Diabetes Metab. Syndr. Obes. 2021 14 3567 3602 10.2147/DMSO.S319895 34413662
    [Google Scholar]
  10. Aiysha Thompson K. Kanamarlapud V. Type 2 diabetes mellitus and glucagon like peptide-1 receptor signalling. Clin. Exp. Pharmacol. 2013 3 4 10.4172/2161‑1459.1000138
    [Google Scholar]
  11. Rehman H. Ullah K. Rasool A. Manzoor R. Yuan Y. Tareen A.M. Kaleem I. Riaz N. Hameed S. Bashir S. Comparative impact of streptozotocin on altering normal glucose homeostasis in diabetic rats compared to normoglycemic rats. Sci. Rep. 2023 13 1 7921 10.1038/s41598‑023‑29445‑8 37193696
    [Google Scholar]
  12. Wong P.L. Zolkeflee N.K.Z. Ramli N.S. Tan C.P. Azlan A. Tham C.L. Shaari K. Abas F. Antidiabetic effect of Ardisia elliptica extract and its mechanisms of action in STZ-NA-induced diabetic rat model via (1)H-NMR-based metabolomics. J. Ethnopharmacol. 2024 318 117015
    [Google Scholar]
  13. Bener A. Al-Ansari A.A. Zirie M. Al-Hamaq A.O.A.A. Is male fertility associated with type 2 diabetes mellitus? Int. Urol. Nephrol. 2009 41 4 777 784 10.1007/s11255‑009‑9565‑6 19381857
    [Google Scholar]
  14. Maresch C.C. Stute D.C. Alves M.G. Oliveira P.F. de Kretser D.M. Linn T. Diabetes-induced hyperglycemia impairs male reproductive function: a systematic review. Hum. Reprod. Update 2018 24 1 86 105 10.1093/humupd/dmx033 29136166
    [Google Scholar]
  15. Farag N.A. Mohamed A.S. El Sayed H.F. Salah E.L. Din E.Y. Tawfik A.R.A. Echinochrome pigment improves male rats’ fertility. Nat. Prod. J. 2022 12 3 e160921188044 10.2174/2210315510999201116205519
    [Google Scholar]
  16. Zhong O. Ji L. Wang J. Lei X. Huang H. Association of diabetes and obesity with sperm parameters and testosterone levels: a meta-analysis. Diabetol. Metab. Syndr. 2021 13 1 109 10.1186/s13098‑021‑00728‑2 34656168
    [Google Scholar]
  17. Egorov E. Pieters C. Korach-Rechtman H. Shklover J. Schroeder A. Robotics, microfluidics, nanotechnology and AI in the synthesis and evaluation of liposomes and polymeric drug delivery systems. Drug Deliv. Transl. Res. 2021 11 2 345 352 10.1007/s13346‑021‑00929‑2 33585972
    [Google Scholar]
  18. Sim S. Wong N. Nanotechnology and its use in imaging and drug delivery (Review). Biomed. Rep. 2021 14 5 42 10.3892/br.2021.1418 33728048
    [Google Scholar]
  19. Adepu S. Ramakrishna S. Controlled drug delivery systems: Current status and future directions. Molecules 2021 26 19 5905 10.3390/molecules26195905 34641447
    [Google Scholar]
  20. Haleem A. Javaid M. Singh R.P. Rab S. Suman R. Applications of nanotechnology in medical field: a brief review. Glob. Health Journal 2023 7 2 70 77 10.1016/j.glohj.2023.02.008
    [Google Scholar]
  21. Soltanzadeh M. Peighambardoust S.H. Ghanbarzadeh B. Mohammadi M. Lorenzo J.M. Chitosan nanoparticles as a promising nanomaterial for encapsulation of pomegranate (Punica granatum L.) peel extract as a natural source of antioxidants. Nanomaterials (Basel) 2021 11 6 1439 10.3390/nano11061439 34072520
    [Google Scholar]
  22. Kumar S. Ye F. Mazinani B. Dobretsov S. Dutta J. Chitosan nanocomposite coatings containing chemically resistant zno–snox core–shell nanoparticles for photocatalytic antifouling. Int. J. Mol. Sci. 2021 22 9 4513 10.3390/ijms22094513 33925962
    [Google Scholar]
  23. Rahaman M.M. Hossain R. Herrera-Bravo J. Islam M.T. Atolani O. Adeyemi O.S. Owolodun O.A. Kambizi L. Daştan S.D. Calina D. Sharifi-Rad J. Natural antioxidants from some fruits, seeds, foods, natural products, and associated health benefits: An update. Food Sci. Nutr. 2023 11 4 1657 1670 10.1002/fsn3.3217 37051367
    [Google Scholar]
  24. Popović-Djordjević J. Quispe C. Giordo R. Kostić A. Katanić Stanković J.S. Tsouh Fokou P.V. Carbone K. Martorell M. Kumar M. Pintus G. Sharifi-Rad J. Docea A.O. Calina D. Natural products and synthetic analogues against HIV: A perspective to develop new potential anti-HIV drugs. Eur. J. Med. Chem. 2022 233 114217 10.1016/j.ejmech.2022.114217 35276425
    [Google Scholar]
  25. Hashem A.H. Saied E. Ali O.M. Selim S. Al Jaouni S.K. Elkady F.M. El-Sayyad G.S. Pomegranate peel extract stabilized selenium nanoparticles synthesis: promising antimicrobial potential, antioxidant activity, biocompatibility, and hemocompatibility. Appl. Biochem. Biotechnol. 2023 195 10 5753 5776 10.1007/s12010‑023‑04326‑y 36705842
    [Google Scholar]
  26. El-Beltagi H.S. Eshak N.S. Mohamed H.I. Bendary E.S.A. Danial A.W. Physical characteristics, mineral content, and antioxidant and antibacterial activities of Punica granatum or Citrus sinensis peel extracts and their applications to improve cake quality. Plants 2022 11 13
    [Google Scholar]
  27. Mo Y. Ma J. Gao W. Zhang L. Li J. Li J. Zang J. Pomegranate peel as a source of bioactive compounds: a mini review on their physiological functions. Front. Nutr. 2022 9 887113 10.3389/fnut.2022.887113 35757262
    [Google Scholar]
  28. Bawazeer S. Rauf A. Nawaz T. Khalil A.A. Javed M.S. Muhammad N. Shah M.A. Punica granatum peel extracts mediated the green synthesis of gold nanoparticles and their detailed in vivo biological activities. Green Process. Synthesis 2021 10 1 882 892 10.1515/gps‑2021‑0080
    [Google Scholar]
  29. Zhao X. Yuan Z. Anthocyanins frolanate (Punica granatum L.) and their role in antioxidant capacities in vitro. Chem. Biodivers. 2021 18 10 e2100399 10.1002/cbdv.202100399 34388293
    [Google Scholar]
  30. Lavoro A. Falzone L. Gattuso G. Salemi R. Cultrera G. Leone G. Scandurra G. Candido S. Libra M. Pomegranate: A promising avenue against the most common chronic diseases and their associated risk factors (Review). Int. J. Funct. Nutrit. 2021 2 2 6 10.3892/ijfn.2021.16
    [Google Scholar]
  31. Jurenka J.S. Therapeutic applications of pomegranate (Punica granatum L.): a review. Altern. Med. Rev. J. Clinic. Therap. 2008 13 2 128 144
    [Google Scholar]
  32. Zarfeshany A. Asgary S. Javanmard S.H. Potent health effects of pomegranate. Adv. Biomed. Res. 2014 3 100 100 24800189
    [Google Scholar]
  33. Virgen-Carrillo C.A. Martínez Moreno A.G. Valdés Miramontes E.H. Potential Hypoglycemic Effect of Pomegranate Juice and Its Mechanism of Action: A Systematic Review. J. Med. Food 2020 23 1 1 11 10.1089/jmf.2019.0069 31397609
    [Google Scholar]
  34. Nikfarjam M. Rashki Ghaleno L. Shahverdi A.H. Mirshahvalad S.H. Ghoreishi S.M. Alizadeh A.R. Effects of Dietary Pomegranate Peel on Antioxidant Gene Expression and DJ-1 Protein Abundance in Ram Testes. Int. J. Fertil. Steril. 2021 15 4 258 262 34913293
    [Google Scholar]
  35. Minisy F.M. Shawki H.H. El Omri A. Massoud A.A. Omara E.A. Metwally F.G. Badawy M.A. Hassan N.A. Hassan N.S. Oishi H. Pomegranate Seeds Extract Possesses a Protective Effect against Tramadol-Induced Testicular Toxicity in Experimental Rats. BioMed Res. Int. 2020 2020 1 12 10.1155/2020/2732958 32219129
    [Google Scholar]
  36. Türk G. Sönmez M. Aydin M. Yüce A. Gür S. Yüksel M. Aksu E.H. Aksoy H. Effects of pomegranate juice consumption on sperm quality, spermatogenic cell density, antioxidant activity and testosterone level in male rats. Clin. Nutr. 2008 27 2 289 296 10.1016/j.clnu.2007.12.006 18222572
    [Google Scholar]
  37. Harakeh S. Almuhayawi M.S. Akefe I.O. Saber S.H. Al Jaouni S.K. Alzughaibi T. Almehmadi Y. Ali S.S. Bharali D.J. Mousa S. Novel Pomegranate-Nanoparticles Ameliorate Cisplatin-Induced Nephrotoxicity and Improves Cisplatin Anti-Cancer Efficacy in Ehrlich Carcinoma Mice Model. Molecules 2022 27 5 1605 10.3390/molecules27051605 35268707
    [Google Scholar]
  38. Monika P. Chandraprabha M.N. Hari Krishna R. Vittal M. Likhitha C. Pooja N. Chaudhary V. C, M. Recent advances in pomegranate peel extract mediated nanoparticles for clinical and biomedical applications. Biotechnol. Genet. Eng. Rev. 2022 1 29 10.1080/02648725.2022.2122299 36117472
    [Google Scholar]
  39. Wang Z. Pan Z. Ma H. Atungulu G.G. Extract of Phenolics From Pomegranate Peels. Open Food Sci. J. 2011 5 1 17 25 10.2174/1874256401105010017
    [Google Scholar]
  40. Pizzino G. Irrera N. Cucinotta M. Pallio G. Mannino F. Arcoraci V. Squadrito F. Altavilla D. Bitto A. Oxidative stress: Harms and benefits for human health. Oxidat. med. cell. longev. 2017 2017 8416763
    [Google Scholar]
  41. Chinedu E. Arome D. Ameh F. A new method for determining acute toxicity in animal models. Toxicol. Int. 2013 20 3 224 226 10.4103/0971‑6580.121674 24403732
    [Google Scholar]
  42. Chen X. Fu X.S. Li C.P. Zhao H.X. ER stress and ER stress-induced apoptosis are activated in gastric SMCs in diabetic rats. World J. Gastroenterol. 2014 20 25 8260 8267 10.3748/wjg.v20.i25.8260 25009401
    [Google Scholar]
  43. Freund B.J. Allen D. Wilmore J.H. Interaction of test protocol and inclined run training on maximal oxygen uptake. Med. Sci. Sports Exerc. 1986 18 5 588 592 10.1249/00005768‑198610000‑00016 3773677
    [Google Scholar]
  44. Herbert V. Lau K. Gottlieb C.W. Bleicher. Coated charcoal immunoassay of insulin. J. Clin. Endocrinol. 1965 25 1375
    [Google Scholar]
  45. Ohkawa H. Ohishi N. Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem. 1979 95 2 351 358 10.1016/0003‑2697(79)90738‑3 36810
    [Google Scholar]
  46. Montgomery H.A.C. Dymock J.F. The determination of nitrite in water. Analyst (Lond.) 1961 86 414 416
    [Google Scholar]
  47. Aebi H. Catalase in vitro. Methods Enzymol. 1984 105 121 126 10.1016/S0076‑6879(84)05016‑3 6727660
    [Google Scholar]
  48. Solomon M.C. Erasmus N. Henkel R.R. In vivo effects of Eurycoma longifolia Jack (Tongkat Ali) extract on reproductive functions in the rat. Andrologia 2014 46 4 339 348 10.1111/and.12082 23464350
    [Google Scholar]
  49. Foreman D. Gaylor L. Evans E. Trella C. A modification of the Roe procedure for determination of fructose in tissues with increased specificity. Anal. Biochem. 1973 56 2 584 590 10.1016/0003‑2697(73)90225‑X 4797275
    [Google Scholar]
  50. Reddy K.V. Bordekar A.D. Spectrophotometric analysis of resazurin reduction test and semen quality in men. Indian J. Exp. Biol. 1999 37 8 782 786 10709326
    [Google Scholar]
  51. Mayer P. Note on hematein and hematoxylin. J. Sci. Microscopy Microscopic 1903 20 409
    [Google Scholar]
  52. Ujah G.A. Nna V.U. Suleiman J.B. Eleazu C. Nwokocha C. Rebene J.A. Imowo M.U. Obi E.O. Amachree C. Udechukwu E.C. Mohamed M. Tert-butylhydroquinone attenuates doxorubicin-induced dysregulation of testicular cytoprotective and steroidogenic genes, and improves spermatogenesis in rats. Sci. Rep. 2021 11 1 5522 10.1038/s41598‑021‑85026‑7 33750916
    [Google Scholar]
  53. Nna V.U. Abu Bakar A.B. Ahmad A. Eleazu C.O. Mohamed M. Oxidative Stress, NF-κB-Mediated Inflammation and Apoptosis in the Testes of Streptozotocin-Induced Diabetic Rats: Combined Protective Effects of Malaysian Propolis and Metformin. Antioxidants 2019 8 10 465
    [Google Scholar]
  54. Huang H-F. Ding G-L. Liu Y. Liu M-E. Pan J-X. Guo M-X. Sheng J-Z. The effects of diabetes on male fertility and epigenetic regulation during spermatogenesis. Asian J. Androl. 2015 17 6 948 953 10.4103/1008‑682X.150844 25814158
    [Google Scholar]
  55. Facondo P. Di Lodovico E. Delbarba A. Anelli V. Pezzaioli L.C. Filippini E. Cappelli C. Corona G. Ferlin A. The impact of diabetes mellitus type 1 on male fertility: Systematic review and meta‐analysis. Andrology 2022 10 3 426 440 10.1111/andr.13140 34904793
    [Google Scholar]
  56. Mohamadi Y. Jameie S.B-e. Akbari M. Staji M. Moradi F. Mokhtari T. Khanehzad M. Hassanzadeh G. Hyperglycemia decreased medial amygdala projections to medial preoptic area in experimental model of Diabetes Mellitus. Acta Med. Iran. 2015 53 1 1 7 25597598
    [Google Scholar]
  57. Heidari H. Abdollahi M. Khani S. Nojavan F. Khani S. Effect of Alpinia officinarum extract on reproductive damages in streptozotocin induced diabetic male rats. J. Diabetes Metab. Disord. 2021 20 1 77 85 10.1007/s40200‑020‑00711‑0 34222060
    [Google Scholar]
  58. Pedersen C. Porsgaard T. Thomsen M. Rosenkilde M.M. Roed N.K. Sustained effect of glucagon on body weight and blood glucose: Assessed by continuous glucose monitoring in diabetic rats. PLoS One 2018 13 3 e0194468 10.1371/journal.pone.0194468 29558502
    [Google Scholar]
  59. Mouri M. Badireddy M. Hyperglycemia. StatPearls. Treasure Island, FL StatPearls Publishing 2023
    [Google Scholar]
  60. Hantzidiamantis P.J. Lappin S.L. Physiology, Glucose. StatPearls. Treasure Island, FL StatPearls Publishing 2023
    [Google Scholar]
  61. Jiang Y.P. Ye R.J. Yang J.M. Liu N. Zhang W.J. Ma L. Sun T. Niu J.G. Zheng P. Yu J.Q. Protective effects of Salidroside on spermatogenesis in streptozotocin induced type-1 diabetic male mice by inhibiting oxidative stress mediated blood-testis barrier damage. Chem. Biol. Interact. 2020 315 108869 10.1016/j.cbi.2019.108869 31682803
    [Google Scholar]
  62. Choudhury A.A. Devi Rajeswari V. Gestational diabetes mellitus - A metabolic and reproductive disorder. Biomed. Pharmacother. 2021 143 112183 10.1016/j.biopha.2021.112183 34560536
    [Google Scholar]
  63. Padhi S. Nayak A.K. Behera A. Type II diabetes mellitus: a review on recent drug based therapeutics. Biomed. Pharmacother. 2020 131 110708 10.1016/j.biopha.2020.110708 32927252
    [Google Scholar]
  64. Wei Q. Qi L. Lin H. Liu D. Zhu X. Dai Y. Waldron R.T. Lugea A. Goodarzi M.O. Pandol S.J. Li L. Pathological Mechanisms in Diabetes of the Exocrine Pancreas: What’s Known and What’s to Know. Front. Physiol. 2020 11 570276 10.3389/fphys.2020.570276 33250773
    [Google Scholar]
  65. Temidayo S.O. Stefan S.P. Diabetes mellitus and male infertility. Asian Pac. J. Reprod. 2018 7 1 6 14 10.4103/2305‑0500.220978
    [Google Scholar]
  66. Grabež M. Škrbić R. Stojiljković M.P. Rudić-Grujić V. Paunović M. Arsić A. Petrović S. Vučić V. Mirjanić-Azarić B. Šavikin K. Menković N. Janković T. Vasiljević N. Beneficial effects of pomegranate peel extract on plasma lipid profile, fatty acids levels and blood pressure in patients with diabetes mellitus type-2: A randomized, double-blind, placebo-controlled study. J. Funct. Foods 2020 64 103692 10.1016/j.jff.2019.103692
    [Google Scholar]
  67. Arun K. Jayamurthy P. Anusha C. Mahesh S. Nisha P. Studies on activity guided fractionation of pomegranate peel extracts and its effect on antidiabetic and cardiovascular protection properties. J. Food process. 2017 41 1 e13108
    [Google Scholar]
  68. Middha S.K. Usha T. Pande V. Pomegranate peel attenuates hyperglycemic effects of alloxan-induced diabetic rats. EXCLI J. 2014 13 223 224 26417256
    [Google Scholar]
  69. Ma J. Han R. Deng P. Qi Y. Liu W. Cui T. Wang S. Effect of diabetes mellitus on semen quality. Int. J. Clin. Exp. Med. 2020 13 10 7910 7919
    [Google Scholar]
  70. Schoeller E.L. Schon S. Moley K.H. The effects of type 1 diabetes on the hypothalamic, pituitary and testes axis. Cell Tissue Res. 2012 349 3 839 847 10.1007/s00441‑012‑1387‑7 22526620
    [Google Scholar]
  71. He Z. Yin G. Li Q.Q. Zeng Q. Duan J. Diabetes mellitus causes male reproductive dysfunction: A review of the evidence and mechanisms. in vivo 2021 35 5 2503 2513
    [Google Scholar]
  72. Ghanbari E. Nejati V. Khazaei M. Antioxidant and protective effects of Royal jelly on histopathological changes in testis of diabetic rats. Int. J. Reprod. Biomed. (Yazd) 2016 14 8 519 526 10.29252/ijrm.14.8.519 27679827
    [Google Scholar]
  73. Ding E.L. Song Y. Malik V.S. Liu S. Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA 2006 295 11 1288 1299 10.1001/jama.295.11.1288 16537739
    [Google Scholar]
  74. Kelly D.M. Jones T.H. Testosterone: a metabolic hormone in health and disease. J. Endocrinol. 2013 217 3 R25 R45 10.1530/JOE‑12‑0455 23378050
    [Google Scholar]
  75. Xia F. Xu X. Zhai H. Meng Y. Zhang H. Du S. Xu H. Wu H. Lu Y. Castration-induced testosterone deficiency increases fasting glucose associated with hepatic and extra-hepatic insulin resistance in adult male rats. Reprod. Biol. Endocrinol. 2013 11 1 106 10.1186/1477‑7827‑11‑106 24238614
    [Google Scholar]
  76. Mitsuhashi K. Senmaru T. Fukuda T. Yamazaki M. Shinomiya K. Ueno M. Kinoshita S. Kitawaki J. Katsuyama M. Tsujikawa M. Obayashi H. Nakamura N. Fukui M. Testosterone stimulates glucose uptake and GLUT4 translocation through LKB1/AMPK signaling in 3T3-L1 adipocytes. Endocrine 2016 51 1 174 184 10.1007/s12020‑015‑0666‑y 26100787
    [Google Scholar]
  77. Sato K. Iemitsu M. Aizawa K. Ajisaka R. Testosterone and DHEA activate the glucose metabolism-related signaling pathway in skeletal muscle. Am. J. Physiol. Endocrinol. Metab. 2008 294 5 E961 E968 10.1152/ajpendo.00678.2007 18349113
    [Google Scholar]
  78. Yao Q. Wang B. An X. Zhang J. Ding L. Testosterone level and risk of type 2 diabetes in men: a systematic review and meta-analysis. Endocr. Connect. 2018 7 1 220 231 10.1530/EC‑17‑0253 29233816
    [Google Scholar]
  79. Johansen J.S. Harris A.K. Rychly D.J. Ergul A. Oxidative stress and the use of antioxidants in diabetes: Linking basic science to clinical practice. Cardiovasc. Diabetol. 2005 4 1 5 10.1186/1475‑2840‑4‑5 15862133
    [Google Scholar]
  80. Moussa S.A. Oxidative stress in diabetes mellitus. Rom. J. Biophys. 2008 18 3 225 236
    [Google Scholar]
  81. Asmat U. Abad K. Ismail K. Diabetes mellitus and oxidative stress-A concise review. Saudi Pharmaceut J. 2016 24 5 547 553
    [Google Scholar]
  82. Sunita R. Sahidan S. Hidayat R. Evaluation of Malondialdehyde in Type 2 Diabetes Mellitus Patients as Oxidative Stress Markers in Bengkulu Population. Bioscientia Medicina. Journal of Biomedicine and Translational Research 2020 4 3
    [Google Scholar]
  83. Condorelli R.A. La Vignera S. Mongioì L.M. Alamo A. Calogero A.E. Diabetes Mellitus and Infertility: Different Pathophysiological Effects in Type 1 and Type 2 on Sperm Function. Front. Endocrinol. (Lausanne) 2018 9 268 10.3389/fendo.2018.00268 29887834
    [Google Scholar]
  84. Asadi N. Bahmani M. Kheradmand A. Rafieian-Kopaei M. The Impact of Oxidative Stress on Testicular Function and the Role of Antioxidants in Improving it: A Review. J. Clin. Diagn. Res. 2017 11 5 IE01 IE05 10.7860/JCDR/2017/23927.9886 28658802
    [Google Scholar]
  85. Patel H. Chen J. Das K.C. Kavdia M. Hyperglycemia induces differential change in oxidative stress at gene expression and functional levels in HUVEC and HMVEC. Cardiovasc. Diabetol. 2013 12 1 142 146 10.1186/1475‑2840‑12‑142 24093550
    [Google Scholar]
  86. Yigitturk G. Acara A.C. Erbas O. Oltulu F. Yavasoglu N.U.K. Uysal A. Yavasoglu A. The antioxidant role of agomelatine and gallic acid on oxidative stress in STZ induced type I diabetic rat testes. Biomed. Pharmacother. 2017 87 240 246 10.1016/j.biopha.2016.12.102 28061407
    [Google Scholar]
  87. Ganjifrockwala F. Joseph J. George G. Decreased total antioxidant levels and increased oxidative stress in South African type 2 diabetes mellitus patients. J. Endocrinol. Metabol. Diabet. South Africa 2017 22 2 21 25
    [Google Scholar]
  88. Matough F.A. Budin S.B. Hamid Z.A. Alwahaibi N. Mohamed J. The Role of Oxidative Stress and Antioxidants in Diabetic Complications = دالمضادة المواد و أكسديالت الإجهاد دور السكري مرض مضاعفات في للأكسدة Sultan Qaboos Univ. Med. J. 2012 12 1 5 18 10.12816/0003082 22375253
    [Google Scholar]
  89. Maphetu N. Unuofin J.O. Masuku N.P. Olisah C. Lebelo S.L. Medicinal uses, pharmacological activities, phytochemistry, and the molecular mechanisms of Punica granatum L. (pomegranate) plant extracts: A review. Biomed. pharmacoth. 2022 153 113256
    [Google Scholar]
  90. Akuru E.A. Chukwuma C.I. Oyeagu C.E. Erukainure O.L. Mashile B. Setlhodi R. Mashele S.S. Makhafola T.J. Unuofin J.O. Abifarin T.O. Mpendulo T.C. Nutritional and phytochemical profile of pomegranate (“Wonderful variety”) peel and its effects on hepatic oxidative stress and metabolic alterations. J. Food Biochem. 2022 46 4 e13913 10.1111/jfbc.13913 34453451
    [Google Scholar]
  91. Sexton W.J. Jarow J.P. Effect of diabetes mellitus upon male reproductive function. Urology 1997 49 4 508 513 10.1016/S0090‑4295(96)00573‑0 9111618
    [Google Scholar]
  92. Luo Z.C. Jin Z.R. Jiang Y.F. Wei T.J. Cao Y.L. Zhang Z. Wei R. Jiang H. The protective effects and underlying mechanisms of dapagliflozin on diabetes-induced testicular dysfunction. Asian J. Androl. 2023 25 3 331 338 10.4103/aja202242 35848706
    [Google Scholar]
  93. La Vignera S. Condorelli R. Vicari E. D’Agata R. Calogero A.E. Diabetes mellitus and sperm parameters. J. Androl. 2012 33 2 145 153 10.2164/jandrol.111.013193 21474785
    [Google Scholar]
  94. Gonzales G.F. Villena A. True corrected seminal fructose level: a better marker of the function of seminal vesicles in infertile men. Int. J. Androl. 2001 24 5 255 260 10.1046/j.1365‑2605.2001.00306.x 11554981
    [Google Scholar]
  95. Marconi M. Pilatz A. Wagenlehner F. Diemer T. Weidner W. Impact of infection on the secretory capacity of the male accessory glands. Int. Braz J Urol 2009 35 3 299 309 10.1590/S1677‑55382009000300006 19538765
    [Google Scholar]
  96. Jebur A.B. El-Sayed R.A. Abdel-Daim M.M. El-Demerdash F.M. Punica granatum (Pomegranate) Peel Extract Pre-Treatment Alleviates Fenpropathrin-Induced Testicular Injury via Suppression of Oxidative Stress and Inflammation in Adult Male Rats. Toxics 2023 11 6 504 10.3390/toxics11060504 37368604
    [Google Scholar]
  97. Salau V.F. Erukainure O.L. Olofinsan K.A. Omotoso B.R. Shahidul Islam M. Pomegranate (P. granatum) fruit juice protects against iron-induced oxidative testicular injury via amelioration of oxidative imbalance and modulation of metabolic indices linked to male infertility. Medicine in Omics 2023 8 100021 10.1016/j.meomic.2023.100021
    [Google Scholar]
/content/journals/ctmc/10.2174/0115680266308882240806175831
Loading
/content/journals/ctmc/10.2174/0115680266308882240806175831
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test