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Effects of grape seed proanthocyanidin extract on side effects of high-dose methylprednisolone administration in male rats

  • Aslihan Sur (Department of Veterinary Medicine, Vocational School of Kepsut, Balikesir University) ;
  • Seda Ifazoglu Mutlu (Department of Animal Nutrition and Nutritional Diseases, Faculty of Veterinary Medicine, Firat University) ;
  • Pinar Tatli Seven (Department of Animal Nutrition and Nutritional Diseases, Faculty of Veterinary Medicine, Firat University) ;
  • Ismail Seven (Department of Plant and Animal Production, Vocational School of Sivrice, Firat University) ;
  • Abdullah Aslan (Department of Biology, Faculty of Science, Firat University) ;
  • Meltem Kizil (Department of Physiology, Faculty of Veterinary Medicine, Firat University) ;
  • Recai Kulaksiz (Department of Reproduction and Artifcial Insemination, Faculty of Veterinary Medicine, Balikesir University) ;
  • Mustafa Hilmi Yaranoglu (Experimental Research Center, Balikesir University) ;
  • Selim Esen (Balikesir Directorate of Provincial Agriculture and Forestry, Republic of Turkey Ministry of Agriculture and Forestry)
  • Received : 2023.01.13
  • Accepted : 2023.05.30
  • Published : 2023.10.15

Abstract

In this study, we investigated the effects of grape seed proanthocyanidin extract (GSPE) against the side effects of high-dose administration of methylprednisolone (MP) in male rats. A total of 32 adult Wistar male albino rats were divided into four groups: (1) control (CON), received standard food only; (2) MP, received standard food +intraperitoneal injection of 60 mg/kg MP on day 7; (3) GSPE, received standard food+200 mg/kg/day GSPE; and (4) MP+GSPE, received standard food+200 mg/kg/day of GSPE+intraperitoneal injection of 60 mg/kg MP on day 7. All animals in the GSPE and GSPE+MP groups were treated once a day by oral gavage for 14 consecutive days. The feed intake of rats in the MP and MP+GSPE groups decreased significantly by 24.14% and 13.52%, respectively (p<0.05). Administration of MP resulted in significant increases in serum concentrations of blood urea nitrogen (p<0.001), glucose (p<0.01), alkaline phosphatase, and adrenocorticotropic hormone (p<0.05). High-dose MP administration significantly reduced catalase (p<0.001) and glutathione peroxidase (p<0.05) concentrations in the liver and kidney tissues of rats, while glutathione concentrations were only reduced in liver tissue (p<0.05). The expression levels of Bcl-2 and TNF-α in liver, kidney, and testicular tissue were significantly increased, while the expression levels of caspase-3 were reduced (p<0.001). Furthermore, sperm concentration was significantly affected by GSPE in rats induced by high-dose MP, and sperm loss was significantly reduced in MP+GSPE (p<0.05). These findings suggest that GSPE could be useful as a supplement to alleviate MP-induced toxicity in rats.

Keywords

Acknowledgement

This research was funded by the Directorate of Scientific Research Projects of Balikesir University, grant number 2020/005.

References

  1. Yao Y, Ding J, Wang Z et al (2020) ROS-responsive polyurethane fibrous patches loaded with methylprednisolone (MP) for restoring structures and functions of infarcted myocardium in vivo. Biomaterials 232:119726. https://doi.org/10.1016/j.biomaterials.2019.119726
  2. Ayyar VS, Almon RR, DuBois DC et al (2017) Functional proteomic analysis of corticosteroid pharmacodynamics in rat liver: Relationship to hepatic stress, signaling, energy regulation, and drug metabolism. J Proteomics 160:84-105. https://doi.org/10.1016/j.jprot.2017.03.007
  3. Nunokawa T, Chinen N, Shimada K et al (2022) Efficacy of sulfasalazine for the prevention of Pneumocystis pneumonia in patients with rheumatoid arthritis: a multicentric self-controlled case series study. J Infect Chemother 29:193-197. https://doi.org/10.1016/j.jiac.2022.10.019
  4. Shorey CL, Mulla RT, Mielke JG (2023) The effects of synthetic glucocorticoid treatment for inflammatory disease on brain structure, function, and dementia outcomes: A systematic review. Brain Res 1798:148157. https://doi.org/10.1016/j.brainres.2022.148157
  5. Samal J, Rebelo AL, Pandit A (2019) A window into the brain: Tools to assess pre-clinical efficacy of biomaterials-based therapies on central nervous system disorders. Adv Drug Deliv Rev 148:68-145. https://doi.org/10.1016/j.addr.2019.01.012
  6. Turjeman K, Yanay N, Elbaz M et al (2019) Liposomal steroid nano-drug is superior to steroids as-is in mdx mouse model of Duchenne muscular dystrophy. Nanomed Nanotechnol Biol Med 16:34-44. https://doi.org/10.1016/j.nano.2018.11.012
  7. Sendrasoa FA, Ranaivo IM, Raherivelo AJ et al (2021) Adverse effects of long-term oral corticosteroids in the department of dermatology, antananarivo, madagascar. Clin Cosmet Investig Dermatol 14:1337-1341. https://doi.org/10.2147/CCID.S332201
  8. Wang L, Yang N, Yang J et al (2022) A review: the manifestations, mechanisms, and treatments of musculoskeletal pain in patients with COVID-19. Front Pain Res 3:826160. https://doi.org/10.3389/fpain.2022.826160
  9. Al Mamun A, Monalisa I, Tul Kubra K et al (2021) Advances in immunotherapy for the treatment of spinal cord injury. Immunobiology 226:152033. https://doi.org/10.1016/j.imbio.2020.152033
  10. Serarslan Y, Yonden Z, Ozgiray E et al (2010) Protective effects of tadalafil on experimental spinal cord injury in rats. J Clin Neurosci 17:349-352. https://doi.org/10.1016/j.jocn.2009.03.036
  11. Hassanzadeh S, Jameie SB, Mehdizadeh M et al (2018) FNDC5 expression in Purkinje neurons of adult male rats with acute spinal cord injury following treatment with methylprednisolone. Neuropeptides 70:16-25. https://doi.org/10.1016/j.npep.2018.05.002
  12. Adamec I, Pavlovic I, Pavicic T et al (2018) Toxic liver injury after high-dose methylprednisolone in people with multiple sclerosis. Mult Scler Relat Disord 25:43-45. https://doi.org/10.1016/j.msard.2018.07.021
  13. Kim MJ, Lim JY, Park SA et al (2018) Effective combination of methylprednisolone and interferon β-secreting mesenchymal stem cells in a model of multiple sclerosis. J Neuroimmunol 314:81-88. https://doi.org/10.1016/j.jneuroim.2017.11.010
  14. Xu J, Chen S, Chen H et al (2009) STAT5 mediates antiapoptotic effects of methylprednisolone on oligodendrocytes. J Neurosci 29:2022-2026. https://doi.org/10.1523/JNEUROSCI.2621-08.2009
  15. Deng G, Dai C, Chen J et al (2018) Porous Se@SiO2 nanocomposites protect the femoral head from methylprednisolone-induced osteonecrosis. Int J Nanomed- 13:1809-1818. https://doi.org/10.2147/IJN.S159776
  16. Mertoglu C, Kiraz ZK, Sogut E, Ozyurt H (2015) Melatonin and a single-high dose methylprednisolone effect on the oxidantantioxidant system in the rabbit heart tissue. Turk J Biochem 40:316-322. https://doi.org/10.1515/tjb-2015-0019
  17. Zhai X, Chen Y, Han X et al (2022) The protective effect of hypericin on postpartum depression rat model by inhibiting the NLRP3 inflammasome activation and regulating glucocorticoid metabolism. Int Immunopharmacol 105:108560. https://doi.org/10.1016/j.intimp.2022.108560
  18. Kadle MAH, Mazurchik NV (2016) Hepatotoxicity induced by high dose of methylprednisolone therapy in a patient with multiple sclerosis: a case report and brief review of literature. Open J Gastroenterol 06:146-150. https://doi.org/10.4236/ojgas.2016.65019
  19. Davidov Y, Har-Noy O, Pappo O et al (2016) Methylprednisolone-induced liver injury: case report and literature review. J Dig Dis 17:55-62. https://doi.org/10.1111/1751-2980.12306
  20. Hasona N, Morsi A (2019) Grape Seed Extract Alleviates Dexamethasone-Induced Hyperlipidemia, Lipid Peroxidation, and Hematological Alteration in Rats. Indian J Clin Biochem 34:213-218. https://doi.org/10.1007/s12291-018-0736-z
  21. Kour G, Haq SA, Bajaj BK et al (2021) Phytochemical add-on therapy to DMARDs therapy in rheumatoid arthritis: In vitro and in vivo bases, clinical evidence and future trends. Pharmacol Res 169:105618. https://doi.org/10.1016/j.phrs.2021.105618
  22. Sica VP, Mahony C, Baker TR (2018) Multi-detector characterization of grape seed extract to enable in silico safety assessment. Front Chem 6:334. https://doi.org/10.3389/fchem.2018.00334
  23. Bijak M, Sut A, Kosiorek A et al (2019) Dual anticoagulant/antiplatelet activity of polyphenolic grape seeds extract. Nutrients 11:93. https://doi.org/10.3390/nu11010093
  24. Coelho MC, Sanchez PKV, Fernandes RR et al (2019) Effect of grape seed extract (GSE) on functional activity and mineralization of OD-21 and MDPC-23 cell lines. Braz Oral Res 33:e013. https://doi.org/10.1590/1807-3107bor-2019.vol33.0013
  25. Yin W, Li B, Li X et al (2015) Anti-inflammatory effects of grape seed procyanidin B2 on a diabetic pancreas. Food Funct 6:3065-3071. https://doi.org/10.1039/c5fo00496a
  26. Liu W, Xu C, Sun X et al (2015) Grape seed proanthocyanidin extract protects against perfluorooctanoic acid-induced hepatotoxicity by attenuating inflammatory response, oxidative stress and apoptosis in mice. Toxicol Res (Camb) 5:224-234. https://doi.org/10.1039/c5tx00260e
  27. Fouad D, Shuker E, Farhood M (2023) Renal toxicity of methylprednisolone in male Wistar rats and the potential protective effect by boldine supplementation. J King Saud Univ Sci 35:102381. https://doi.org/10.1016/j.jksus.2022.102381
  28. Bashir N, Shagirtha K, Manoharan V, Miltonprabu S (2019) The molecular and biochemical insight view of grape seed proanthocyanidins in ameliorating cadmium-induced testes-toxicity in rat model: implication of PI3K/Akt/Nrf-2 signaling. Biosci Rep 39:BSR20180515. https://doi.org/10.1042/BSR20180515
  29. Hu C, Shen S, Zhang A et al (2014) The liver protective effect of methylprednisolone on a new experimental acute-on-chronic liver failure model in rats. Dig Liver Dis 46:928-935. https://doi.org/10.1016/j.dld.2014.06.008
  30. Kosciuszko M, Poplawska-Kita A, Pawlowski P et al (2021) Clinical relevance of estimating circulating interleukin-17 and interleukin-23 during methylprednisolone therapy in Graves' orbitopathy: a preliminary study. Adv Med Sci 66:315-320. https://doi.org/10.1016/j.advms.2021.07.002
  31. Buttgereit F, Da Silva JPA, Boers M et al (2002) Standardised nomenclature for glucocorticoid dosages and glucocorticoid treatment regimens: current questions and tentative answers in rheumatology. Ann Rheum Dis 61:718-722. https://doi.org/10.1136/ard.61.8.718
  32. Placer ZA, Cushman LL, Johnson BC (1966) Estimation of product of lipid peroxidation (malonyl dialdehyde) in biochemical systems. Anal Biochem 16:359-364. https://doi.org/10.1016/0003-2697(66)90167-9
  33. Sedlak J, Lindsay RH (1968) Estimation of total, proteinbound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem 25:192-205. https://doi.org/10.1016/0003-2697(68)90092-4
  34. Lawrence RA, Burk RF (1976) Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Commun 71:952-958. https://doi.org/10.1016/0006-291x(76)90747-6
  35. Aebi H (1974) Catalase. In: Bergmeyer HU (ed) Methods of enzymatic analysis, 2nd edn. Academic Press, pp 673-684
  36. Aslan A, Gok O, Erman O, Kuloglu T (2018) Ellagic acid impedes carbontetrachloride-induced liver damage in rats through suppression of NF-kB, Bcl-2 and regulating Nrf-2 and caspase pathway. Biomed Pharmacother 105:662-669. https://doi.org/10.1016/j.biopha.2018.06.020
  37. Aslan A, Gok O, Beyaz S et al (2022) Royal jelly regulates the caspase, Bax and COX-2, TNF-α protein pathways in the fluoride exposed lung damage in rats. Tissue Cell 76:101754. https://doi.org/10.1016/j.tice.2022.101754
  38. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680-685. https://doi.org/10.1038/227680a0
  39. Aslan A, Beyaz S, Gok O, Erman O (2020) The effect of ellagic acid on caspase-3/bcl-2/Nrf-2/NF-kB/TNF-α /COX-2 gene expression product apoptosis pathway: a new approach for muscle damage therapy. Mol Biol Rep 47:2573-2582. https://doi.org/10.1007/s11033-020-05340-7
  40. Varisli O, Agca C, Agca Y (2013) Short-term storage of rat sperm in the presence of various extenders. J Am Assoc Lab Anim Sci 52:732-737
  41. Sonmez M, Turk G, Yuce A (2005) The effect of ascorbic acid supplementation on sperm quality, lipid peroxidation and testosterone levels of male Wistar rats. Theriogenology 63:2063-2072. https://doi.org/10.1016/j.theriogenology.2004.10.003
  42. Turk G, Atessahin A, Sonmez M et al (2007) Lycopene protects against cyclosporine A-induced testicular toxicity in rats. Theriogenology 67:778-785. https://doi.org/10.1016/j.theriogenology.2006.10.013
  43. Hasona NA, Morsi A, Alghabban AA (2018) The impact of grape proanthocyanidin extract on dexamethasone-induced osteoporosis and electrolyte imbalance. Comp Clin Path 27:1213-1219. https://doi.org/10.1007/s00580-018-2724-3
  44. Mohamadpour M, Mollajani R, Sarabandi F, Hosseini F (2020) Protective effect of grape seed extract on dexamethasone- induced testicular toxicity in mice. Crescent J Med Biol Sci 7:59-65
  45. Maniam J, Morris MJ (2012) The link between stress and feeding behaviour. Neuropharmacology 63:97-110. https://doi.org/10.1016/j.neuropharm.2012.04.017
  46. Fang J, Dubois DC, He Y et al (2011) Dynamic modeling of methylprednisolone effects on body weight and glucose regulation in rats. J Pharmacokinet Pharmacodyn 38:293-316. https://doi.org/10.1007/s10928-011-9194-4
  47. Novelli M, Pocai A, Chiellini C et al (2008) Free fatty acids as mediators of adaptive compensatory responses to insulin resistance in dexamethasone-treated rats. Diabetes Metab Res Rev 24:155-164. https://doi.org/10.1002/dmrr.785
  48. Hasona NA, Alrashidi AA, Aldugieman TZ et al (2017) Vitis vinifera extract ameliorate hepatic and renal dysfunction induced by dexamethasone in albino rats. Toxics 5:11. https://doi.org/10.3390/toxics5020011
  49. Figueiredo BS, Ferreira FBD, Barbosa AM et al (2021) Coadministration of sitagliptin or metformin has no major impact on the adverse metabolic outcomes induced by dexamethasone treatment in rats. Life Sci 286:120026. https://doi.org/10.1016/j.lfs.2021.120026
  50. Ayroldi E, Migliorati G, Riccardi C (2022) Immunomodulatory and anti-inflammatory properties of glucocorticoids. In: Kenakin T (ed) Comprehensive pharmacology. Elsevier, pp 394-421
  51. Abdelhamid AM, Elsheakh AR, Abdelaziz RR, Suddek GM (2020) Empagliflozin ameliorates ethanol-induced liver injury by modulating NF-κB/Nrf-2/PPAR-γ interplay in mice. Life Sci 256:117908. https://doi.org/10.1016/j.lfs.2020.117908
  52. Zengin M, Sur A, Ilhan Z et al (2022) Effects of fermented distillers grains with solubles, partially replaced with soybean meal, on performance, blood parameters, meat quality, intestinal fora, and immune response in broiler. Res Vet Sci 150:58-64. https://doi.org/10.1016/j.rvsc.2022.06.027
  53. Sur A, Zengin M, Bacaksiz OK et al (2023) Performance, blood biochemistry, carcass fatty acids, antioxidant status, and HSP70 gene expressions in Japanese quails reared under high stocking density: the effects of grape seed powder and meal. Trop Anim Health Prod 55:53. https://doi.org/10.1007/s11250-023-03481-y
  54. Weiss MJ, Henthorn PS, Lafferty MA et al (1986) Isolation and characterization of a cDNA encoding a human liver/bone/kidney-type alkaline phosphatase. Proc Natl Acad Sci U S A 83:7182-7186. https://doi.org/10.1073/pnas.83.19.7182
  55. Raja A, Singh GP, Fadil SA et al (2022) Prophylactic anti-osteoporotic effect of Matricaria chamomilla L. flower using steroid-induced osteoporosis in rat model and molecular modelling approaches. Antioxidants 11:1316. https://doi.org/10.3390/antiox11071316
  56. Osuntokun OS, Olayiwola G, Atere TG et al (2020) Graded doses of grape seed methanol extract attenuated hepato-toxicity following chronic carbamazepine treatment in male Wistar rats. Toxicol Reports 7:1592-1596. https://doi.org/10.1016/j.toxrep.2020.11.006
  57. Yalcin E, Cavusoglu K (2022) Toxicity assessment of potassium bromate and the remedial role of grape seed extract. Sci Rep 12:20529. https://doi.org/10.1038/s41598-022-25084-7
  58. Dores RM (2009) Adrenocorticotropic hormone, melanocyte-stimulating hormone, and the melanocortin receptors: Revisiting the work of Robert Schwyzer: a thirty-year retrospective. Ann N Y Acad Sci 1163:93-100. https://doi.org/10.1111/j.1749-6632.2009.04434.x
  59. Hu D, Li J, Zhuang Y, Mao X (2021) Adrenocorticotropic hormone: An expansion of our current understanding of the treatment for nephrotic syndrome. Steroids 176:108930. https://doi.org/10.1016/j.steroids.2021.108930
  60. Catania A, Gatti S, Colombo G, Lipton JM (2004) Targeting melanocortin receptors as a novel strategy to control inflammation. Pharmacol Rev 56:1-29. https://doi.org/10.1124/pr.56.1.1
  61. Qi D, Rodrigues B (2007) Glucocorticoids produce whole body insulin resistance with changes in cardiac metabolism. Am J Physiol - Endocrinol Metab 292:654-667. https://doi.org/10.1152/ajpendo.00453.2006
  62. Albayrak S, Atci IB, Kalayci M et al (2015) Effect of carnosine, methylprednisolone and their combined application on irisin levels in the plasma and brain of rats with acute spinal cord injury. Neuropeptides 52:47-54. https://doi.org/10.1016/j.npep.2015.06.004
  63. Li SG, Ding YS, Niu Q et al (2015) Grape seed proanthocyanidin extract alleviates arsenic-induced oxidative reproductive toxicity in male mice. Biomed Environ Sci 28:272-280. https://doi.org/10.3967/bes2015.038
  64. Tian M, Liu F, Liu H et al (2018) Grape seed procyanidins extract attenuates Cisplatin-induced oxidative stress and testosterone synthase inhibition in rat testes. Syst Biol Reprod Med 64:246-259. https://doi.org/10.1080/19396368.2018.1450460
  65. Shin M, Yoon S, Moon J (2010) The proanthocyanidins inhibit dimethylnitrosamine-induced liver damage in rats. Arch Pharm Res 33:167-173. https://doi.org/10.1007/s12272-010-2239-1
  66. Abbaszadeh F, Fakhri S, Khan H (2020) Targeting apoptosis and autophagy following spinal cord injury: therapeutic approaches to polyphenols and candidate phytochemicals. Pharmacol Res 160:105069
  67. Beattie MS, Hermann GE, Rogers RC, Bresnahan JC (2002) Cell death in models of spinal cord injury. Prog Brain Res 137:37-47. https://doi.org/10.1016/S0079-6123(02)37006-7
  68. Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495-516. https://doi.org/10.1080/01926230701320337
  69. Song Q, Shi Z, Bi W et al (2015) Beneficial effect of grape seed proanthocyanidin extract in rabbits with steroid-induced osteonecrosis via protecting against oxidative stress and apoptosis. J Orthop Sci 20:196-204. https://doi.org/10.1007/s00776-014-0654-8
  70. Wang EH, Yu L, Bu J et al (2019) Grape seed proanthocyanidin extract alleviates high-fat diet induced testicular toxicity in rats. RSC Adv 9:11842-11850. https://doi.org/10.1039/c9ra01017c
  71. Mohi-ud-din R, Lone NA, Malik TA et al (2022) Bioactivity guided isolation and characterization of anti-hepatotoxic markers from Berberis pachyacantha Koehne. Pharmacol Res Mod Chinese Med 4:100144. https://doi.org/10.1016/j.prmcm.2022.100144
  72. Kandhare AD, Bodhankar SL, Mohan V, Thakurdesai PA (2015) Effect of glycosides based standardized fenugreek seed extract in bleomycin-induced pulmonary fibrosis in rats: decisive role of Bax, Nrf2, NF-κB, Muc5ac, TNF-α and IL-1β. Chem Biol Interact 237:151-165. https://doi.org/10.1016/j.cbi.2015.06.019
  73. Mogilner JG, Elenberg Y, Lurie M et al (2006) Effect of dexamethasone on germ cell apoptosis in the contralateral testis after testicular ischemia-reperfusion injury in the rat. Fertil Steril 85:1111-1117. https://doi.org/10.1016/j.fertnstert.2005.10.021
  74. Nayak BS, Rao KM, Shetty SD et al (2013) Terminal bifurcation of the right testicular vein and left testicular arterio-venous anastomosis. Kathmandu Univ Med J 11:168-170. https://doi.org/10.3126/kumj.v11i2.12496
  75. Hameed U, Iqbal S, Rehman F, Hassan A (2020) Effect of exogenous and endogenous glucocorticoids on the spermatogenesis of albino rats; A comparative study. Ann Abbasi Shaheed Hosp Karachi Med Dent Coll 25:151-157 https://doi.org/10.58397/ashkmdc.v25i3.364
  76. Dolatabadi AA, Zarchii SR (2015) The effect of prescription of different dexamethasone doses on reproductive system. Biomed Res 26:656-660
  77. Su L, Deng Y, Zhang Y et al (2011) Protective effects of grape seed procyanidin extract against nickel sulfate-induced apoptosis and oxidative stress in rat testes. Toxicol Mech Methods 21:487-494. https://doi.org/10.3109/15376516.2011.556156