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Erschienen in: Comparative Clinical Pathology 6/2020

04.09.2020 | Original Article

D-ribose-L-cysteine improves hormonal imbalance, spermatogenic dysregulation, and redox status in streptozotocin-diabetic rats

verfasst von: Victor Okoliko Ukwenya, Toluwase Solomon Olawuyi, Sunday Aderemi Adelakun, Oluwole Israel Ogunsola, Moses Ugbede Ukwenya

Erschienen in: Comparative Clinical Pathology | Ausgabe 6/2020

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Abstract

D-ribose-L-cysteine is a pro-drug that is derived from L-cysteine which is reported to upsurge the cellular levels of glutathione. Diabetes mellitus is a metabolic disease that causes oxidative imbalance resulting in an impairment of the steroidogenic function and reproductive dysfunctions. This study is to investigate the potency of D-ribose-L-cysteine in reversing hyperglycemia and reproductive histopathological alterations in streptozotocin-diabetic rats. Diabetes was induced in adult male Wistar rats with a single intraperitoneal injection of 70 mg/kg b.w. streptozotocin. The hyperglycemic rats were thereafter treated orally with D-ribose-L-cysteine (100 mg/kg b.w.) and metformin (30 mg/kg b.w.) respectively once daily for a period of 17 days. Blood glucose concentration, reproductive hormonal assays, seminal fluid analysis, testicular anti-oxidant enzymes, tissue protein, and histopathological investigations were done to determine the effects of D-ribose-L-cysteine in streptozotocin-diabetic rats. Treatment with D-ribose-L-cysteine was associated with reduction in blood glucose concentration, increased body weight, increased tissue protein, reduced lipid peroxidation, and increase in anti-oxidant enzymes compared with the diabetic control. D-ribose-L-cysteine-treated rats also showed improved tubular cellularity and cytoarchitectural integrity relative to the diabetic control. In this study, D-ribose-L-cysteine, a synthetic pro-drug, proved to be able to reverse endocrine imbalance and spermatogenic alterations associated with diabetes by eliminating oxidative stress.
Literatur
Zurück zum Zitat Adaramoye OA, Lawal SO (2014) Effect of kolaviron, a biflavonoid complex from G arcinia kola seeds, on the antioxidant, hormonal and spermatogenic indices of diabetic male rats. Androl. 46(8):878–886CrossRef Adaramoye OA, Lawal SO (2014) Effect of kolaviron, a biflavonoid complex from G arcinia kola seeds, on the antioxidant, hormonal and spermatogenic indices of diabetic male rats. Androl. 46(8):878–886CrossRef
Zurück zum Zitat Adedara IA, Awogbindin IO, Anamelechi JP, Farombi EO (2015) Garcinia kola seed ameliorates renal, hepatic, and testicular oxidative damage in streptozotocin-induced diabetic rats. Pharm Biol 53(5):695–704CrossRef Adedara IA, Awogbindin IO, Anamelechi JP, Farombi EO (2015) Garcinia kola seed ameliorates renal, hepatic, and testicular oxidative damage in streptozotocin-induced diabetic rats. Pharm Biol 53(5):695–704CrossRef
Zurück zum Zitat Adedara IA, Okpara ES, Busari EO, Omole O, Owumi SE, Farombi EO (2019) Dietary protocatechuic acid abrogates male reproductive dysfunction in streptozotocin-induced diabetic rats via suppression of oxidative damage, inflammation and caspase-3 activity. Eur J Pharmacol 849:30–42CrossRef Adedara IA, Okpara ES, Busari EO, Omole O, Owumi SE, Farombi EO (2019) Dietary protocatechuic acid abrogates male reproductive dysfunction in streptozotocin-induced diabetic rats via suppression of oxidative damage, inflammation and caspase-3 activity. Eur J Pharmacol 849:30–42CrossRef
Zurück zum Zitat Artimani T, Amiri I, Soleimani Asl S, Saidijam M, Hasanvand D, Afshar S (2018) Amelioration of diabetes-induced testicular and sperm damage in rats by cerium oxide nanoparticle treatment. Androl. 50(9):e13089CrossRef Artimani T, Amiri I, Soleimani Asl S, Saidijam M, Hasanvand D, Afshar S (2018) Amelioration of diabetes-induced testicular and sperm damage in rats by cerium oxide nanoparticle treatment. Androl. 50(9):e13089CrossRef
Zurück zum Zitat Asadi N, Kheradmand A, Gholami M, Moradi FH (2018) Effect of ghrelin on the biochemical and histopathology parameters and spermatogenesis cycle following experimental varicocele in rat. Androl. 50(10):e13106CrossRef Asadi N, Kheradmand A, Gholami M, Moradi FH (2018) Effect of ghrelin on the biochemical and histopathology parameters and spermatogenesis cycle following experimental varicocele in rat. Androl. 50(10):e13106CrossRef
Zurück zum Zitat Badr MO, Edrees NM, Abdallah AA, El-Deen NA, Neamat-Allah AN, Ismail HT (2011) Anti-tumour effects of Egyptian propolis on Ehrlich ascites carcinoma. Vet Ital 47(3):341–350PubMed Badr MO, Edrees NM, Abdallah AA, El-Deen NA, Neamat-Allah AN, Ismail HT (2011) Anti-tumour effects of Egyptian propolis on Ehrlich ascites carcinoma. Vet Ital 47(3):341–350PubMed
Zurück zum Zitat Beutler E, Duron O, Kelly BM (1963) Improved method for the determination of blood glutathione. J Lab Clin Med 61:882–888PubMed Beutler E, Duron O, Kelly BM (1963) Improved method for the determination of blood glutathione. J Lab Clin Med 61:882–888PubMed
Zurück zum Zitat Couto N, Malys N, Gaskell SJ, Barber J (2013) Partition and turnover of glutathione reductase from Saccharomyces cerevisiae: a proteomic approach. J Proteome Res 12(6):2885–2894CrossRef Couto N, Malys N, Gaskell SJ, Barber J (2013) Partition and turnover of glutathione reductase from Saccharomyces cerevisiae: a proteomic approach. J Proteome Res 12(6):2885–2894CrossRef
Zurück zum Zitat Dalle-Donne I, Rossi R, Colombo G, Giustarini D, Milzani A (2009) Protein S-glutathionylation: a regulatory device from bacteria to humans. Trends Biochem Sci 34(2):85–96CrossRef Dalle-Donne I, Rossi R, Colombo G, Giustarini D, Milzani A (2009) Protein S-glutathionylation: a regulatory device from bacteria to humans. Trends Biochem Sci 34(2):85–96CrossRef
Zurück zum Zitat Dalvi SM, Patil VW, Ramraje NN (2012) The roles of glutathione, glutathione peroxidase, glutathione reductase and the carbonyl protein in pulmonary and extra pulmonary tuberculosis. J Clin Diagn Res: JCDR 6(9):1462–1465PubMed Dalvi SM, Patil VW, Ramraje NN (2012) The roles of glutathione, glutathione peroxidase, glutathione reductase and the carbonyl protein in pulmonary and extra pulmonary tuberculosis. J Clin Diagn Res: JCDR 6(9):1462–1465PubMed
Zurück zum Zitat Dröge W (2005) Oxidative stress and ageing: is ageing a cysteine deficiency syndrome? Philosophical Transactions of the Royal Society B: Biological Sciences 360(1464):2355–2372CrossRef Dröge W (2005) Oxidative stress and ageing: is ageing a cysteine deficiency syndrome? Philosophical Transactions of the Royal Society B: Biological Sciences 360(1464):2355–2372CrossRef
Zurück zum Zitat Ekerbicer N, Gurpinar T, Sisman AR, Guvendi G, Camsari UM, Uysal N (2018) Statins reduce testicular and ocular VEGF: a potential compromise to microcirculation. Microvasc Res 119:60–63CrossRef Ekerbicer N, Gurpinar T, Sisman AR, Guvendi G, Camsari UM, Uysal N (2018) Statins reduce testicular and ocular VEGF: a potential compromise to microcirculation. Microvasc Res 119:60–63CrossRef
Zurück zum Zitat Falana B, Adelek O, Orenolu M, Osinubi A, Oyewopo A (2017) Effect of D-ribose-L-cysteine on aluminum induced testicular damage in male Sprague-Dawley rats. JBRA Assist. Reprod 21(2):94PubMedPubMedCentral Falana B, Adelek O, Orenolu M, Osinubi A, Oyewopo A (2017) Effect of D-ribose-L-cysteine on aluminum induced testicular damage in male Sprague-Dawley rats. JBRA Assist. Reprod 21(2):94PubMedPubMedCentral
Zurück zum Zitat Gumieniczek A, Hopkała H, Wojtowicz Z, Nieradko M (2001) Differences in antioxidant status in skeletal muscle tissue in experimental diabetes. Clin Chim Acta 314(1–2):39–45CrossRef Gumieniczek A, Hopkała H, Wojtowicz Z, Nieradko M (2001) Differences in antioxidant status in skeletal muscle tissue in experimental diabetes. Clin Chim Acta 314(1–2):39–45CrossRef
Zurück zum Zitat Ibrahim MN, Asalah AK, Abd-Alaleem DI, Moursi SMM (2013) Effect of ghrelin on testicular functions in streptozotocin induced type 1 diabetic rats. Int J Diabetes Res 2013(6):101–111 Ibrahim MN, Asalah AK, Abd-Alaleem DI, Moursi SMM (2013) Effect of ghrelin on testicular functions in streptozotocin induced type 1 diabetic rats. Int J Diabetes Res 2013(6):101–111
Zurück zum Zitat Ighodaro OM, Akinloye OA (2018) First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): their fundamental role in the entire antioxidant defence grid. Alexandria Med J 54(4):287–293CrossRef Ighodaro OM, Akinloye OA (2018) First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): their fundamental role in the entire antioxidant defence grid. Alexandria Med J 54(4):287–293CrossRef
Zurück zum Zitat Jaiswal YS, Tatke PA, Gabhe SY, Vaidya AB (2017) Antidiabetic activity of extracts of Anacardium occidentale Linn. Leaves on n-streptozotocin diabetic rats. J Tradit Complement Med 7(4):421–427CrossRef Jaiswal YS, Tatke PA, Gabhe SY, Vaidya AB (2017) Antidiabetic activity of extracts of Anacardium occidentale Linn. Leaves on n-streptozotocin diabetic rats. J Tradit Complement Med 7(4):421–427CrossRef
Zurück zum Zitat Kulkarni CP, Bodhankar SL, Ghule AE, Mohan V, Thakurdesai, PA (2012) Antidiabetic activity of Trigonella foenumgraecum L. seeds extract (IND01) in neonatal streptozotocin-induced (n-STZ) rats. Diabetol Croat 41(1) Kulkarni CP, Bodhankar SL, Ghule AE, Mohan V, Thakurdesai, PA (2012) Antidiabetic activity of Trigonella foenumgraecum L. seeds extract (IND01) in neonatal streptozotocin-induced (n-STZ) rats. Diabetol Croat 41(1)
Zurück zum Zitat Long L, Qiu H, Cai B, Chen N, Lu X, Zheng S, Ye X, Li Y (2018) Hyperglycemia induced testicular damage in type 2 diabetes mellitus rats exhibiting microcirculation impairments associated with vascular endothelial growth factor decreased via PI3K/Akt pathway. Oncotarget 9(4):5321–5336CrossRef Long L, Qiu H, Cai B, Chen N, Lu X, Zheng S, Ye X, Li Y (2018) Hyperglycemia induced testicular damage in type 2 diabetes mellitus rats exhibiting microcirculation impairments associated with vascular endothelial growth factor decreased via PI3K/Akt pathway. Oncotarget 9(4):5321–5336CrossRef
Zurück zum Zitat Misra HP, Fridovich I (1972) The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 247(10):3170–3175PubMed Misra HP, Fridovich I (1972) The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 247(10):3170–3175PubMed
Zurück zum Zitat Mohammed A, Pandey KB, Rizvi SI (2017) Effect of phytochemicals on diabetes-related neurological disorders. Neuroprotective effects of phytochemicals in neurological disorders. Wiley-Blackwell publishers, Hoboken 283–298 Mohammed A, Pandey KB, Rizvi SI (2017) Effect of phytochemicals on diabetes-related neurological disorders. Neuroprotective effects of phytochemicals in neurological disorders. Wiley-Blackwell publishers, Hoboken 283–298
Zurück zum Zitat Nagasawa HT (2015) inventor; Max International, Llc, assignee. Method to enhance delivery of glutathione and ATP levels in cells. United States patent application US 14/838,274; p. 27 Nagasawa HT (2015) inventor; Max International, Llc, assignee. Method to enhance delivery of glutathione and ATP levels in cells. United States patent application US 14/838,274; p. 27
Zurück zum Zitat Nguyen BP, Pham HN, Tran H, Nghiem N, Nguyen QH, Do TTT, Tran CT, Simpson CR (2019) Predicting the onset of type 2 diabetes using wide and deep learning with electronic health records. Comput Methods Prog Biomed 182:105055CrossRef Nguyen BP, Pham HN, Tran H, Nghiem N, Nguyen QH, Do TTT, Tran CT, Simpson CR (2019) Predicting the onset of type 2 diabetes using wide and deep learning with electronic health records. Comput Methods Prog Biomed 182:105055CrossRef
Zurück zum Zitat Osinubi AAA, Medubi LJ, Akang EN, Sodiq LK, Samuel TA, Kusemiju T, … Fasanmade O (2018) A comparison of the anti-diabetic potential of D-ribose-L-cysteine with insulin, and oral hypoglycaemic agents on pregnant rats. Toxicol. Rep 832–838. 1 Osinubi AAA, Medubi LJ, Akang EN, Sodiq LK, Samuel TA, Kusemiju T, … Fasanmade O (2018) A comparison of the anti-diabetic potential of D-ribose-L-cysteine with insulin, and oral hypoglycaemic agents on pregnant rats. Toxicol. Rep 832–838. 1
Zurück zum Zitat Rezaei N, Mardanshahi T, Shafaroudi MM, Abedian S, Mohammadi H, Zare Z (2018) Effects of L-carnitine on the follicle-stimulating hormone, luteinizing hormone, testosterone, and testicular tissue oxidative stress levels in streptozotocin-induced diabetic rats. J. Evid.-Based Integr. Med. 23: 2515690X18796053 Rezaei N, Mardanshahi T, Shafaroudi MM, Abedian S, Mohammadi H, Zare Z (2018) Effects of L-carnitine on the follicle-stimulating hormone, luteinizing hormone, testosterone, and testicular tissue oxidative stress levels in streptozotocin-induced diabetic rats. J. Evid.-Based Integr. Med. 23: 2515690X18796053
Zurück zum Zitat Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG (1973) Selenium: biochemical role as a component of glutathione peroxidase. Science 179(4073):588–590CrossRef Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG (1973) Selenium: biochemical role as a component of glutathione peroxidase. Science 179(4073):588–590CrossRef
Zurück zum Zitat Saleh RA, Agarwal A (2002) Oxidative stress and male infertility: from research bench to clinical practice. J Androl 23(6):737–752PubMed Saleh RA, Agarwal A (2002) Oxidative stress and male infertility: from research bench to clinical practice. J Androl 23(6):737–752PubMed
Zurück zum Zitat Salem FS, Badr MOT, Neemat-Allah ANF (2011) Biochemical and pathological studies on the effects of levamisole and chlorambucil on Ehrlich ascites carcinoma-bearing mice. Vet Ital 47(3):341–350 Salem FS, Badr MOT, Neemat-Allah ANF (2011) Biochemical and pathological studies on the effects of levamisole and chlorambucil on Ehrlich ascites carcinoma-bearing mice. Vet Ital 47(3):341–350
Zurück zum Zitat Salmani M, Aalizadeh A, Moghimi S, Tarverdizadeh B, Akbarzadeh S, Ashtiyani SC, Azarbayjani M (2015) Studying the effects aqueous extract of Urtica dioica and swimming training on the histochemical properties of liver in diabetic rats. J Chem Pharm Res 7(1):654–660 Salmani M, Aalizadeh A, Moghimi S, Tarverdizadeh B, Akbarzadeh S, Ashtiyani SC, Azarbayjani M (2015) Studying the effects aqueous extract of Urtica dioica and swimming training on the histochemical properties of liver in diabetic rats. J Chem Pharm Res 7(1):654–660
Zurück zum Zitat Sawiress FA, Ziada MS, Bebawy WS, Amer HA (2011) Effect of ginseng extract supplementation on testicular functions in diabetic rats. Endocr Regul 45(3):139–148CrossRef Sawiress FA, Ziada MS, Bebawy WS, Amer HA (2011) Effect of ginseng extract supplementation on testicular functions in diabetic rats. Endocr Regul 45(3):139–148CrossRef
Zurück zum Zitat Stefek M, Sonikova R, Okruhlicova L, Volkovova K, Kucharska J, Gajdosik A et al (2000) Effect of dietary supplementation with the pyridoindole antioxidant stobadine on antioxidant state and ultrastructure of diabetic rat myocardium. Acta Diabetol 37(3):111–117CrossRef Stefek M, Sonikova R, Okruhlicova L, Volkovova K, Kucharska J, Gajdosik A et al (2000) Effect of dietary supplementation with the pyridoindole antioxidant stobadine on antioxidant state and ultrastructure of diabetic rat myocardium. Acta Diabetol 37(3):111–117CrossRef
Zurück zum Zitat Ukwenya VO, Ashaolu JO, Adeyemi AO, Akinola OA, Caxton-Martins EA (2012) Antihyperglycemic activities of methanolic leaf extract of Anacardium occidentale (Linn.) on the pancreas of streptozotocin-induced diabetic rats. J Cell Anim Biol 6(11):169–174CrossRef Ukwenya VO, Ashaolu JO, Adeyemi AO, Akinola OA, Caxton-Martins EA (2012) Antihyperglycemic activities of methanolic leaf extract of Anacardium occidentale (Linn.) on the pancreas of streptozotocin-induced diabetic rats. J Cell Anim Biol 6(11):169–174CrossRef
Zurück zum Zitat Ukwenya V, Ashaolu O, Adeyemi D, Obuotor E, Tijani A, Biliaminu A, Caxton-Martins E (2013) Evaluation of antioxidant potential of methanolic leaf extract of Anacardium occidentale (Linn) on the testes of streptozotocin-induced diabetic Wistar rats. Eur J Anat 17(2):72–81 Ukwenya V, Ashaolu O, Adeyemi D, Obuotor E, Tijani A, Biliaminu A, Caxton-Martins E (2013) Evaluation of antioxidant potential of methanolic leaf extract of Anacardium occidentale (Linn) on the testes of streptozotocin-induced diabetic Wistar rats. Eur J Anat 17(2):72–81
Zurück zum Zitat Varshney R, Kale RK (1990) Effects of calmodulin antagonists on radiation-induced lipid peroxidation in microsomes. Int J Radiat Biol 58(5):733–743CrossRef Varshney R, Kale RK (1990) Effects of calmodulin antagonists on radiation-induced lipid peroxidation in microsomes. Int J Radiat Biol 58(5):733–743CrossRef
Zurück zum Zitat World Health Organization. WHO (2010) Laboratory manual for the examination of human semen and semen-cervical mucus interaction. Camb. Univ. Press. Cambridge, UK World Health Organization. WHO (2010) Laboratory manual for the examination of human semen and semen-cervical mucus interaction. Camb. Univ. Press. Cambridge, UK
Metadaten
Titel
D-ribose-L-cysteine improves hormonal imbalance, spermatogenic dysregulation, and redox status in streptozotocin-diabetic rats
verfasst von
Victor Okoliko Ukwenya
Toluwase Solomon Olawuyi
Sunday Aderemi Adelakun
Oluwole Israel Ogunsola
Moses Ugbede Ukwenya
Publikationsdatum
04.09.2020
Verlag
Springer London
Erschienen in
Comparative Clinical Pathology / Ausgabe 6/2020
Print ISSN: 1618-5641
Elektronische ISSN: 1618-565X
DOI
https://doi.org/10.1007/s00580-020-03155-3

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