D-Ribose-L-Cysteine Attenuated Polychlorinated Biphenyls Mediated Neuroendocrine-Transmembrane Ionic Pump ATPase Disruption and Peroxynitrite Formation in a Rat Model: A Possible Role of Testicular Antioxidant and Androgenic Enzymes

Authors

  • Oyovwi Mega Obukohwo Department of Hunan Physiology, Achievers University, Owo, Ondo341104, Nigeria https://orcid.org/0000-0002-8892-0770
  • Tesi Prince Edesiri Department of Science Laboratory Technology, Delta State Polytechnic, Ogwashi-Uku, Delta State 320001, Nigeria
  • Ben-Azu Benneth Department of Pharmacology, Faculty of Basic Medical Science, College of Health Sciences, Delta State University, Abraka, Delta State 330106, Nigeria
  • Emojevwe Victor Department of Physiology, University of Medical Sciences, Ondo, Ondo State 351104, Nigeria
  • Ojetola Abodunrin Adebayo Department of Physiology, Adeleke University, Ede Osun State, Nigeria
  • Joseph G. Uchechukwu Department of Medical Laboratory Science, Adeleke University, Ede Osun, State, Nigeria
  • Onome Bright Oghenetega Department of Physiology, School of Basic Medical Science, Babcock University Ilishan Remo, Ikenne 121103, Nigeria
  • Rotu Arientare Rume Department of Physiology, University of Ibadan, Ibadan,Oyo State, Nigeria
  • Ovuakporaye Irikefe Simon Department of Physiology, Faculty of Basic Medical Science, College of Health Sciences, Delta State University, Abraka, Delta State 330106, Nigeria
  • Ejime Agbonifo-Chijiokwu Department of Physiology, Faculty of Basic Medical Science, College of Health Sciences, Delta State University, Abraka, Delta State 330106, Nigeria
  • Nwangwa Eze Kingsley Department of Physiology, Faculty of Basic Medical Science, College of Health Sciences, Delta State University, Abraka, Delta State 330106, Nigeria
  • Falajiki Yewande Faith Department of Physiology, Adeleke University, Ede Osun State, Nigeria
  • Okwute Patrick Godwin Department of Physiology, School of Basic Medical Science, Babcock University Ilishan Remo, Ikenne 121103, Nigeria

DOI:

https://doi.org/10.48048/tis.2023.5879

Keywords:

DRLC, PCBs, Ionic pump, Peroxynitrite, Sulphyldryl, HOST, Peroxiredoxin-4, Neuroendocrine

Abstract

The very hazardous and persistent aquatic pollutants known as polychlorinated biphenyls (PCBs) are known to bioaccumulate in a range of marine mammals. Human and animal studies have shown that exposure to PCBs affects the male reproductive system. This study was conducted to investigate the therapeutic effects of D-ribose-L-cysteine (DRLC) on PCB-mediated ATPase disruption of the neuroendocrine transmembrane ion pump and peroxynitrite formation in rat models. After the first 15 days of PCB treatment, DRLC (50 mg/kg) was administered orally for 15 days, beginning on day 16 and continuing through day 30. PCB (2 mg/kg) was administered for 30 days. All tests were performed in accordance with accepted procedures. Kisspeptin (kissp), gonadotropin-releasing hormone alkaline phosphatase (ALP), lactate dehydrogenase (LDH), glutathione peroxidase (GSH-Px), and total antioxidant capacity (TAOC) were all analyzed in blood on day 31. The testes were also removed and sent for testosterone, testicular antioxidant enzymes (L-C and PrDx-4), androgenic enzymes (3β-HSD and 17β-HSD), sulfhydryl content, and transmembrane ion pump (Na+, K+, Ca2+, Mg2+, and H+ ions) The results of the study showed that Kisspeptin, GnRH, Testosterone, L-C, PrDx-4, 3-HSD, 17-HSD, HOST, Na+, K+, Ca2+, Mg2+, and H+-ATPase levels were significantly increased by DRLC. In addition, DRLC therapy dramatically reduced levels of ONOO-, H2O2, 8-OHdG, ALP, and LDH, while increasing TAOC to restore GSH-Px levels. The results of the present study suggest that DRLC is a potentially effective therapeutic approach to reduce PCB-induced neuroendocrine transmembrane ion pump disruption in an experimental rat model. The primary mechanism underlying this effect may be its antioxidant activities against the formation of peroxynitrite and elevated levels of hydrogen peroxide.

HIGHLIGHTS

  • DRLC abates PCBs-induced peroxynitrite stress in rats’ testes
  • DRLC abates PCBs-induced sulphydryl depletion in rats’ testes
  • DRLC ameliorated PCB-induced alteration in testicular ionic ATPase pumps
  • DRLC enhances testicular antioxidant enzymes in rats treated with PCBs
  • DRLC reversed PCB-induced decreased spermatogenesis in rats’ testes


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References

WR Folland, JL Newsted, SD Fitzgerald, PC Fuchsman, PW Bradley, J Kern, K Kannan, RE Remington and MJ Zwiernik. Growth and reproductive effects from dietary exposure to Aroclor 1268 in mink (Neovison vison), a surrogate model for marine mammals. Environ. Toxicol. Chem. 2016; 35, 604-18.

S Liu, S Li and Y Du. Polychlorinated biphenyls (PCBs) enhance metastatic properties of breast cancer cells by activating rho-associated kinase (ROCK). PLos One 2010; 5, 11272.

SJ Stuart-Smith and PD Jepson. Persistent threats need persistent counteraction: Responding to PCB pollution in marine mammals. Mar. Pol. 2017; 84, 69-75.

PD Jepson, R Deaville, JL Barber, L AguilarL, A Borrell, S Murphy, J Barry, A Brownlow, J Barnett, S Berrow, AA Cunningham, NJ Davison, MTDoeschate, R Esteban, M Ferreira, AD Foote, T Genov, J Giménez, J Loveridge and RJ Law. PCB pollution continues to impact populations of orcas and other dolphins in European waters. Sci. Rep. 2016; 6, 18573.

S Murphy, JL Barber, JA Learmonth, FL Read, R Deaville, MW Perkins, A Brownlow, N Davison, R Penrose, GJ Pierce, RJ Law and PD Jepson. Reproductive failure in UK Harbourporpoises phocoenaphocoena: Legacy of pollutant exposure? PLos One 2015; 10, e0131085.

R Williams, MT Doeschate, DJ Curnick, A Brownlow, JL Barber, NJ Davison, R Deaville, M Perkins, PD Jepson and S Jobling. Levels of polychlorinated biphenyls are still associated with toxic effects in harbor porpoises (Phocoenaphocoena) despite having fallen below proposed toxicity thresholds. Environ. Sci. Tech. 2020; 54, 2277-86.

LH Schwacke, EO Voit, LJ Hansen, RS Wells, GB Mitchum, AA Hohn and PA Fair. Probabilistic risk assessment of reproductive effects of polychlorinated biphenyls on bottlenose dolphins (Tursiops truncatus) from the Southeast United States coast. Environ. Toxicol. Chem. 2002; 21, 2752-64.

A Goncharov, R Rej, S Negoita, M Schymura, A Santiago-Rivera, G Morse,ATF Environment and DO Carpenter.Lower serum testosterone associated with elevated polychlorinated biphenyl concentrations in native American men. Environ. Health Perspect. 2009; 117, 1454-60.

JD Meeker and R Hauser. Exposure to polychlorinated biphenyls (PCBs) and male reproduction. Syst. Biol. Reprod. Med. 2010; 56, 122-31.

ZA Ahmed, AN Abtar, HH Othman and TA Aziz. Effects of quercetin, sitagliptin alone or in combination in testicular toxicity induced by doxorubicin in rats. Drug Des. Dev. Ther. 2019; 13, 3321-9.

SNKuriyama and IChahoud. In utero exposure to low-dose 2,3',4,4',5-pentachlorobiphenyl (PCB 118) impairs male fertility and alters neurobehavior in rat offspring. Toxicology 2004; 202, 185-97.

O Emokpae, B Ben-Azu, AM Ajayi and S Umukoro. D-Ribose-l-cysteine attenuates lipopolysaccharide-induced memory deficits through inhibition of oxidative stress, release of proinflammatory cytokines, and nuclear factor-kappa B expression in mice. N. Schmied. Arch. Pharmacol. 2020; 393, 909-25.

B Falana, O Adeleke, M Orenolu, A Osinubiand A Oyewopo. Effect of D-ribose-L-cysteine on aluminum induced testicular damage in male sprague-dawleyrats. JBRA Assist. Reprod. 2017; 21, 94-100.

VO Ukwenya, TS Olawuyi, AM Adam and MU Ukwenya. Hormonal changes and redox imbalance in nicotine-induced testicular toxicity: The mitigating influence of D-ribose-l-cysteine. J. Basic Appl. Zool. 2020; 81, 1-11.

LJ Medubi, NC Nwosu, RO Lawal, OO Medubi, C Ama, OT Kusemijuand AA Osinubi. Increased de novo glutathione production enhances sexual dysfunctions in rats subjected to paradoxical sleep deprivation. JBRA Assist. Reprod. 2021; 25, 215-22.

AA Sunday, O Babatunde, PF Obinna and AA Adewale. Nutritional supplementation of D-ribose-L-cysteine suppresses oxidative stress, spermatogenesis and steroidogenesis recovery in rats exposed to mercury chloride: histomorphometry and biochemical evidence. Endocrinol. Metabol. 2021; 4, 100105.

T Kader, CM Porteous, GT Jones, N Dickerhof, VK Narayana, D Tull, S Taraknathand McCormick. S. P. A. (. Ribose-cysteine protects against the development of atherosclerosis in apoE-deficient mice. PLos One 2020; 15, e0228415.

GO Oludare, GO Afolayan and GG Semidara. Potential anti-toxic effect of D-ribose-l-cysteine supplement on the reproductive functions of male rats administered cyclophosphamide. J. Basic Clin. Physiol. Pharmacol. 2021; 32, 925-33.

MO Oyovwi, B Ben-Azu, TP Edesiri, E VictoE, RA Rotu, QE Ozegbe, EK Nwangwa, V Atuadu and OG Adebayo. Kolaviron abates busulfan-induced episodic memory deficit and testicular dysfunction in rats: The implications for neuroendopathobiological changes during chemotherapy. Biomed. Pharmacother. 2021; 142, 112022.

MO Oyovwi, B Ben-Azu, EP Tesi, AA Oyeleke, CI Uruaka, RA Rotu and EO Aya-Ebi. Repeated endosulfan exposure induces changes in neurochemicals, decreases ATPase transmembrane ionic-pumps, and increased oxidative/nitrosative stress in the brains of rats: Reversal by quercetin. Pestic. Biochem. Physiol. 2021; 175, 104833.

P Venkataraman, M Sridhar, S Dhanammal, M Vijayababu, N Srinivasan and J Arunakaran. Antioxidant role of zinc in PCB (Aroclor 1254) exposed ventral prostate of albino rats.J. Nutr. Biochem. 2004; 15, 608-13.

MO Oyovwi, EK Nwangwa, B Ben-Azu, RA Rotue, TP Edesiri, V Emojevwe, JC Igweh and CL Uruaka. Prevention and reversal of chlorpromazine induced testicular dysfunction in rats by synergistic testicle-active flavonoids, taurine and coenzyme-10. Reprod. Toxicol. 2021; 101, 50-62.

S Hjerténand H Pan. Purification and characterization of two forms of a low-affinity Ca2+−ATPase from erythrocyte membranes. Biochim. Biophys. Acta 1983; 728, 281-8.

R Jeyendran, H Ven, S Rachagan, M Perez-Peiea and L Zaneveld. Semen quality and in-vitro fertilization. Aust. New Zeal. J. Obstet. Gynaecol. 1989; 29, 168-72.

MH Fourie, MS Bornman and E Viljoen. Epididymal markers in rats exposed to the xenoestrogen p-nonylphenol: No biochemical effects at low dosages. Andrologia 2001; 33, 305-10.

J Sedlak and RH Lindsay. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal. Biochem. 1968; 25, 192-205.

MJ Olusoji, OM Oyeyemi, ER Asenuga, TO Omobowale, OL Ajayi and AA Oyagbemi. Protective effect of Gallic acid on doxorubicin‐induced testicular and epididymal toxicity. Andrologia 2017; 49, e12635.

MS Chang, WN Kim, WM Yang, HY Kim, JH Oh and SK Park. Cytoprotective effects of Morinda officinalis against hydrogen peroxide‐induced oxidative stress in Leydig TM3 cells. Asian J. Androl.2008; 10, 667-74.

GM Raso, R Meli, O Gualillo, M Pacilio and RD Carlo. Prolactin induction of nitric oxide synthase in rat c6 glioma cells. J. Neurochem. 2021; 73, 2272-7.

SA Adelakun, B Ogunlade, OP Fidelis and AA Ajao. Nutritional supplementation of D-Ribose-L-cysteine suppresses oxidative stress, spermatogenesis and steroidogenesis recovery in rats exposed to mercury chloride: Histomorphometry and biochemical evidence. Endocrinol. Metabol. 2021; 4, 100105.

V Emojevwe, AO Naiho, EK Nwangwa, MO Oyovwi, KKAnachuna, E Agbanifo-Chijiokwu and TME Daubry. Duration-dependent effects of high dose of phthalate exposure on semen quality in adult male rats. JBRA Assist. Reprod. 2022; 26, 53.

MO Oyovwi, EK Nwangwa, AR Rotu and V Emojevwe. The concept of male reproductive anatomy. In: W Wu (Ed.). Male Reproductive Anatomy. IntechOpen, London, 2021.

KJ Darney and L Ewing. Autoregulation of testosterone secretion in perfused rat testes. Endocrinology 1981; 109, 993-5.

S Roychoudhury, S Chakraborty, AP Choudhury, A Das, NK Jha, P Slama, M Nath, P Massanyi, J Ruokolainen and KK Kesari. Environmental factors-induced oxidative stress: Hormonal and molecular pathway disruptions in hypogonadism and erectile dysfunction. Antioxidants 2021; 10, 837.

MS Malo, SN Alam, G Mostafa, SJ Zeller, PV Johnson, N Mohammad, KT Chen, AK Moss, S Ramasamy, A Faruqui, S Hodin, PS Malo, F Ebrahimi, B Biswas, S Narisawa, JL Millan, HS Warren, JB Kaplan, CL Kitts andRA Hodin. Intestinal alkaline phosphatase preserves the normal homeostasis of gut microbiota. Gut 2010; 59, 1476-84.

L Bessueille, A Briolay, J Como,SMebarek, C Mansouri, M Gleizes, AE Jamal, R Buchet, C Dumontet, E Matera, E Mornet, J Millan, C Fonta and D Magne. Tissue-nonspecific alkaline phosphatase is an anti-inflammatory nucleotidase. Bone 2020; 133, 115262.

S Cocco, A Secondo, ADViscovo, C Procaccini, L Formisano, C Franco, A Esposito, A Scorziello, G Matarese, GD Renzo and LMT Canzoniero. Polychlorinated biphenyls induce mitochondrial dysfunction in SH-SY5Y neuroblastoma cells. PLos One 2015; 10, e0129481.

AM Kabel. Zinc/alogliptin combination attenuates testicular toxicity induced by doxorubicin in rats: Role of oxidative stress, apoptosis and TGF-β1/NF-κB signaling. Biomed. Pharmacother. 2018; 97, 439-49.

A Chattopadhyay, R Sengupta and SParveen. Antigonadaleffects of terminalia arjuna in male albino rats. Res. J. Med. Plant 2014; 8, 82-91.

S Bavithra, K Selvakumar, R Pratheepa Kumari, G Krishnamoorthy, PVenkataraman and J Arunakaran. Polychlorinated biphenyl (PCBs)-induced oxidative stress plays a critical role on cerebellar dopaminergic receptor expression: Ameliorative role of quercetin. Neurotoxicity Res. 2011; 21, 149-59.

RA Loiola, FMD Anjos, AL Shimada, WS Cruz, CC Drewes, SF Rodrigues, KHM Cardozo, VM Carvalho, E Pinto and SH Farsky. Long-term in vivo polychlorinated biphenyl 126 exposure induces oxidative stress and alters proteomic profile on islets of Langerhans. Sci. Rep. 2016; 6, 27882.

MR Pillai, KT Keylock, HC Cromwell and LA Meserve. Exercise influences the impact of polychlorinated biphenyl exposure on immune function. PLos One 2020; 15, e0237705.

P Murugesan, J Senthilkumar, K Balasubramanian, MM Aruldhasand J Arunakaran. Impact of polychlorinated biphenyl Aroclor 1254 on testicular antioxidant system in adult rats. Hum. Exp. Toxicol. 2005; 24, 61-6.

T Kader, CM Porteous, GT Jones, N Dickerhof, VK Narayana, D Tull, S Taraknath and SPA McCormick.Ribose-cysteine protects against the development of atherosclerosis in apoE-deficient mice. PLos One 2020; 15, e0228415.

A Agarwal, G Virk, C Ong and SSD Plessis. Effect of oxidative stress on male reproduction. World J. Mens Health 2014; 32, 1-17.

CR Franci, JA Anselmo-Franc and SM McCann. The role of endogenous atrial natriuretic peptide in resting and stress-induced release of corticotropin, prolactin, growth hormone, and thyroid-stimulating hormone. Proc. Natl. Acad. Sci. Unit. States Am. 1992; 89, 11391-5.

P Kaur and MP BansaL. Effect of selenium-induced oxidative stress on the cell kinetics in testis and reproductive ability of male mice. Nutrition 2005; 21, 351-7.

G Sanchez, ANT Nguyen, B Timmerberg, JS Tash and G Blanco. The Na,K-ATPase α4 isoform from humans has distinct enzymatic properties and is important for sperm motility. Mol. Hum. Reprod. 2006; 12, 565-76.

M Murali, MS CarvalhoL and T Shivanandappa. Oxidative stress-mediated cytotoxicity of Endosulfan is causally linked to the inhibition of NADH dehydrogenase and Na+, K+ATPase in Ehrlich ascites tumor cells.Mol. Cell. Biochem. 2020; 468, 59-6.

S Sinha, G Kumar and M Laloraya. Abnormal physical architecture of the lipophilic domains of human sperm membrane in oligospermia: A logical cause for low fertility profiles. Biochem. Biophys. Res. Comm. 1994; 198, 266-73.

PE Visconti.Understanding the molecular basis of sperm capacitation through kinase design. Proc. Natl. Acad. Sci. 2009; 106, 667-8.

MO Oyovwi, BO Oghenetega, V Emojevwe, YF Falajiki and GJ Uchechukwu. Quercetin protects against levetiracetam induced gonadotoxicity in rats. Toxicology 2023; 491, 153518.

MT Yakubu, MA Akanji and AT Oladiji. Evaluation of antiandrogenic potentials of aqueous extract of Chromolaena odoratum (L.) K. R. leaves in male rats. Andrologia 2007; 39, 235-43.

J Yang, C Pi and G Wang. Inhibition of PI3K/Akt/mTOR pathway by apigenin induces apoptosis and autophagy in hepatocellular carcinoma cells. Biomed. Pharmacother. 2018; 103, 699-707.

A Hisatomi, S Sakuma, M Fujiwara and J Seki. Effect of tacrolimus on the cauda epididymis in rats: Analysis of epididymal biochemical markers or antioxidant defense enzymes. Toxicology 2008; 243, 23-30.

Y Iuchi, F Okada, S Tsunoda, N Kibe, N Shirasawa, M Ikawa, M Okabe, Y Ikeda and J Fujii. Peroxiredoxin 4 knockout results in elevated spermatogenic cell death via oxidative stress. Biochem. J. 2009; 419, 149-58.

MO Oyovwi, TP Edesiri, E Victor, NE Kingsley, RA Rume, FY Faith, OI Simon, BO Oghenetega and E Agbonifo‐Chijiokwu. D‐ribose‐L‐cysteine abrogates testicular maladaptive responses induced by polychlorinated bisphenol intoxication in rats via activation of the mTOR signaling pathway mediating inhibition of apoptosis, inflammation, and oxidonitrergic flux. J.Biochem. Mol. Toxicol. 2022; 36, e23161.

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2023-08-15

How to Cite

Obukohwo, O. M. ., Edesiri, T. P. ., Benneth, B.-A. ., Victor, E. ., Adebayo, O. A. ., Uchechukwu, J. G. ., Oghenetega, O. B. ., Rume, R. A. ., Simon, O. I. ., Agbonifo-Chijiokwu, E. ., Kingsley, N. E. ., Faith, F. Y. ., & Godwin, O. P. . (2023). D-Ribose-L-Cysteine Attenuated Polychlorinated Biphenyls Mediated Neuroendocrine-Transmembrane Ionic Pump ATPase Disruption and Peroxynitrite Formation in a Rat Model: A Possible Role of Testicular Antioxidant and Androgenic Enzymes. Trends in Sciences, 20(10), 5879. https://doi.org/10.48048/tis.2023.5879

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Vol. 20 No. 10 (2023): Trends in Sciences, Volume 20, Number 10, October 2023

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Research Articles

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