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Kolaviron suppresses dysfunctional reproductive axis associated with multi-walled carbon nanotubes exposure in male rats

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Abstract

Reproductive toxicity associated with excessive exposure to multi-walled carbon nanotubes (MWCNTs), which are commonly used in medicine as valuable drug delivery systems, is well documented. Kolaviron, a bioflavonoid isolated from Garcinia kola seeds, elicits numerous health beneficial effects related to its anti-inflammatory, anti-genotoxic activities, anti-apoptotic, and antioxidant properties. However, information on the role of kolaviron in MWCNTs-induced reproductive toxicity is not available in the literature. Herein, we assessed the protective effects of kolaviron on MWCNTs-induced dysfunctional reproductive axis in rats following exposure to MWCNTs (1 mg/kg) and concurrent treatment with kolaviron (50 or 100 mg/kg body weight) for 15 successive days. Results showed that MWCNTs-induced dysfunctional reproductive axis as evidenced by deficits in pituitary and testicular hormones, marker enzymes of testicular function, and sperm functional characteristics were abrogated in rats co-administered with kolaviron. Moreover, co-administration of kolaviron-abated MWCNTs-induced inhibition of antioxidant enzyme activities increases in oxidative stress and inflammatory indices. This is evidenced by diminished levels of tumor necrosis factor-alpha, nitric oxide, lipid peroxidation, reactive oxygen, and nitrogen species as well as reduced activity of myeloperoxidase in testes, epididymis, and hypothalamus of the rats. Biochemical data on the chemoprotection of MWCNTs-induced reproductive toxicity were corroborated by histological findings. Taken together, kolaviron suppressed dysfunctional reproductive axis associated with MWCNTs exposure via abrogation of oxidative stress and inflammation in male rats.

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References

  • Adaramoye OA, Lawal SO (2014) Effect of kolaviron, a biflavonoid complex from Garcinia kola seeds, on the antioxidant, hormonal and spermatogenic indices of diabetic male rats. Andrologia 46:878–886

    CAS  Google Scholar 

  • Adedara IA, Vaithinathan S, Jubendradass R, Mathur PP, Farombi EO (2013) Kolaviron prevents carbendazim-induced steroidogenic dysfunction and apoptosis in testes of rats. Environ Toxicol Pharmacol 35:444–453

    CAS  Google Scholar 

  • Adedara IA, Ebokaiwe AP, Mathur PP, Farombi EO (2014) Nigerian bonny light crude oil induces endocrine disruption in male rats. Drug Chem Toxicol 37:198–203

    CAS  Google Scholar 

  • Adedara IA, Owoeye O, Aiyegbusi MA, Dagunduro JO, Daramola YM, Farombi EO (2015) Kolaviron protects against benzo[a]pyrene-induced functional alterations along the brain-pituitary-gonadal axis in male rats. Environ Toxicol Pharmacol 40:459–470

    CAS  Google Scholar 

  • Adedara IA, Abolaji AO, Rocha JBT, Farombi EO (2016) Diphenyl diselenide protects against mortality, locomotor deficits and oxidative stress in Drosophila melanogaster model of manganese-induced neurotoxicity. Neurochem Res 41:1430–1438

    CAS  Google Scholar 

  • Adedara IA, Anao OO, Forcados GE, Awogbindin IO, Agbowo A, Ola-Davies OE, Patlolla AK, Tchounwou PB, Farombi EO (2018) Low doses of multi-walled carbon nanotubes elicit hepatotoxicity in rats with markers of oxidative stress and induction of pro-inflammatory cytokines. Biochem Biophys Res Commun 503(4):3167–3173

    CAS  Google Scholar 

  • 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 849:30–42

    CAS  Google Scholar 

  • Adedara IA, Awogbindin IO, Owoeye O, Maduako IC, Ajeleti AO, Owumi SE, Patlolla AK, Farombi EO (2020) Kolaviron via anti-inflammatory and redox regulatory mechanisms abates multi-walled carbon nanotubes-induced neurobehavioral deficits in rats. Psychopharmacology 237:1027–1040

    Google Scholar 

  • Akinmoladun AC, Akinrinola BL, Olaleye MT, Farombi EO (2015) Kolaviron, a Garcinia kola biflavonoid complex, protects against ischemia/reperfusion injury: pertinent mechanistic insights from biochemical and physical evaluations in rat brain. Neurochem Res 40:777–787

    CAS  Google Scholar 

  • Anatoliotakis N, Deftereos S, Bouras G, Giannopoulos G, Tsounis D, Angelidis C, Kaoukis A, Stefanadis C (2013) Myeloperoxidase: expressing inflammation and oxidative stress in cardiovascular disease. Curr Top Med Chem 13:115–1138

    CAS  Google Scholar 

  • Bancroft JD, Gamble M (2008) Theory and practice of histology techniques (6th ed.). Churchill Livingstone Elsevier, Philadelphia, pp 83–134

    Google Scholar 

  • Baskaran S, Finelli R, Agarwal A, Henkel R (2020) Reactive oxygen species in male reproduction: a boon or a bane? Andrologia:e13577. https://doi.org/10.1111/and.13577

  • Blazak WF, Trienen KA, Juniewicz PE (1993) Application of testicular sperm head counts in the assessment of male reproductive toxicity. In: Chapin RE, Heindel J. (eds), Methods in Toxiciology, vol 3A., Male reproductive toxicology Academic Press, San Diego, pp 86–94

  • Bradford MM (1976) Rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  CAS  Google Scholar 

  • Brunauer S, Emmett PH, Teller E (1938) Adsorption of gases in multi-molecular layers. J Am Chem Soc 60:309–319

    CAS  Google Scholar 

  • Chauhan A, Sillu D, Agnihotri S (2019) Removal of pharmaceutical contaminants in wastewater using nanomaterials: a comprehensive review. Curr Drug Metab 20:483–505

    CAS  Google Scholar 

  • Chowdhury M, Kabir SN, Pal AK, Pakrashi A (1983) Modulation of luteinizing hormone receptors: effect of an inhibitor of prolactin secretion, p-coumaric acid. J Endocrinol 98:307–311

    CAS  Google Scholar 

  • Claiborne A (1995) Catalase activity. In: Greewald AR (ed) Handbook of methods for oxygen radical research. CRC Press, Boca Raton, pp 237–242

    Google Scholar 

  • Clavijo RI, Hsiao W (2018) Update on male reproductive endocrinology. Transl Androl Urol 7(Suppl 3):S367–S372

    Google Scholar 

  • Ding T, Li W, Li J (2019) Influence of multi-walled carbon nanotubes on the toxicity and removal of carbamazepine in diatom Navicula sp. Sci Total Environ 697:134104. https://doi.org/10.1016/j.scitotenv.2019.134104

    Article  CAS  Google Scholar 

  • Ema M, Gamo M, Honda K (2016a) Developmental toxicity of engineered nanomaterials in rodents. Toxicol Appl Pharmacol 299:47–52

    CAS  Google Scholar 

  • Ema M, Hougaard KS, Kishimoto A, Honda K (2016b) Reproductive and developmental toxicity of carbon-based nanomaterials: a literature review. Nanotoxicology 10:391–412

    CAS  Google Scholar 

  • Farombi EO, Nwaokeafor IA (2005) Anti-oxidant mechanisms of kolaviron: studies on serum lipoprotein oxidation, metal chelation and oxidative membrane damage in rats. Clin Exp Pharmacol Physiol 32:667–674

    CAS  Google Scholar 

  • Farombi EO, Tahnteng JG, Agboola AO, Nwankwo JO, Emerole GO (2000) Chemoprevention of 2-acetylaminofluorene-induced hepatotoxicity and lipid peroxidation in rats by kolaviron-a Garcinia kola seed extract. Food Chem Toxicol 38:535–541

    CAS  Google Scholar 

  • Farombi EO, Adedara IA, Oyenihi AB, Ekakitie E, Kehinde S (2013) Hepatic, testicular and spermatozoa antioxidant status in rats chronically treated with Garcinia kola seed. J Ethnopharmacol 146:536–542

    CAS  Google Scholar 

  • Farombi EO, Adedara IA, Forcados GE, Anao OO, Agbowo A, Patlolla AK (2016) Responses of testis, epididymis, and sperm of pubertal rats exposed to functionalized multiwalled carbon nanotubes. Environ Toxicol 31:543–551

    CAS  Google Scholar 

  • Farombi EO, Awogbindin IO, Farombi TH, Oladele JO, Izomoh ER, Aladelokun OB, Ezekiel IO, Adebambo OI, Abah VO (2019) Neuroprotective role of kolaviron in striatal redo-inflammation associated with rotenone model of Parkinson’s disease. Neurotoxicology 73:132–141

    CAS  Google Scholar 

  • Fischer S, Ehlert U, Amiel CR (2019) Hormones of the hypothalamic-pituitary-gonadal (HPG) axis in male depressive disorders - a systematic review and meta-analysis. Front Neuroendocrinol 55:100792. https://doi.org/10.1016/j.yfrne.2019.100792

    Article  CAS  Google Scholar 

  • Fukushima S, Kasai T, Umeda Y, Ohnishi M, Sasaki T, Matsumoto M (2018) Carcinogenicity of multi-walled carbon nanotubes: challenging issue on hazard assessment. J Occup Health 60:10–30

    CAS  Google Scholar 

  • Ganzoury MA, Chidiac C, Kurtz J, de Lannoy CF (2020) CNT-sorbents for heavy metals: electrochemical regeneration and closed-loop recycling. J Hazard Mater 393:122432. https://doi.org/10.1016/j.jhazmat.2020.122432

    Article  CAS  Google Scholar 

  • Ghanbari F, Nasarzadeh P, Seydi E, Ghasemi A, Taghi Joghataei M, Ashtari K, Akbari M (2017) Mitochondrial oxidative stress and dysfunction induced by single- and multiwall carbon nanotubes: a comparative study. J Biomed Mater Res A 105:2047–2055

    CAS  Google Scholar 

  • Granell S, Gironella M, Bulbena O, Panés J, Mauri M, Sabater L, Aparisi L, Gelpí E, Closa D (2003) Heparin mobilizes xanthine oxidase and induces lung inflammation in acute pancreatitis. Crit Care Med 31:525–530

    CAS  Google Scholar 

  • Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite and [15 N] nitrate in biological fluids. Anal Biochem 126:131–138

    CAS  Google Scholar 

  • Guerriero G, Trocchia S, Abdel-Gawad FK, Ciarcia G (2014) Roles of reactive oxygen species in the spermatogenesis regulation. Front Endocrinol (Lausanne) 5:56. https://doi.org/10.3389/fendo.2014.00056

    Article  Google Scholar 

  • Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione S-transferase. The first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130–7139

    CAS  Google Scholar 

  • Han YG, Xu J, Li ZG, Ren GG, Yang Z (2012) In vitro toxicity of multiwalled carbon nanotubes in C6 rat glioma cells. Neurotoxicology 33:1128–1134

    CAS  Google Scholar 

  • Iwu MM (1985) Antihepatoxic constituents of Garcinia kola seeds. Experientia 41(5):699–700

    CAS  Google Scholar 

  • Jollow DJ, Mitchell JR, Zampaglione N, Gillette JR (1974) Bromobenzene induced liver necrosis: protective role of glutathione and evidence for 3,4 bromobenzene oxide as the hepatotoxic metabolite. Pharmacology 11:151–169

    CAS  Google Scholar 

  • Kamran U, Heo YJ, Lee JW, Park SJ (2019) Functionalized carbon materials for electronic devices: a review. Micromachines (Basel) 10(4). https://doi.org/10.3390/mi10040234

  • Kehinde A, Adefisan A, Adebayo O, Adaramoye O (2016) Biflavonoid fraction from Garcinia kola seed ameliorates hormonal imbalance and testicular oxidative damage by anti-tuberculosis drugs in Wistar rats. J Basic Clin Physiol Pharmacol 27:393–401

    CAS  Google Scholar 

  • Klumpp C, Kostarelos K, Prato M, Bianco A (2006) Functionalized carbon nanotubes as emerging nanovectors for the delivery of therapeutics. Biochim Biophys Acta 1758:404–412

    CAS  Google Scholar 

  • Kobayashi N, Izumi H, Morimoto Y (2017) Review of toxicity studies of carbon nanotubes. J Occup Health 59:394–407

    CAS  Google Scholar 

  • Kumar R, Dhanawat M, Kumar S, Singh BN, Pandit JK, Sinha VR (2014) Carbon nanotubes: a potential concept for drug delivery applications. Recent Patents Drug Deliv Formul 8:12–26

    CAS  Google Scholar 

  • Li J, Ying GG, Jones KC, Martin FL (2015) Real-world carbon nanoparticle exposures induce brain and gonadal alterations in zebrafish (Danio rerio) as determined by biospectroscopy techniques. Analyst. 140:2687–2695

    CAS  Google Scholar 

  • Malymy M, Horecker BL (1966) Alkaline phosphatase. In: Methods in Enzymology Volume IX. Academy Press, New York, pp 639–642

    Google Scholar 

  • Misra HP, Fridovich I (1972) The role of superoxide anion in the autooxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 247:3170–3175

    CAS  Google Scholar 

  • Morris PL, Saxena BB (1980) Dose- and age-dependent effects of prolactin (PRL) on luteinizing hormone- and PRL-binding sites in rat leydig cell homogenates. Endocrinology 107:1639–1645

    CAS  Google Scholar 

  • Ncibi MC, Sillanpää M (2017) Optimizing the removal of pharmaceutical drugs carbamazepine and dorzolamide from aqueous solutions using mesoporous activated carbons and multi-walled carbon nanotubes. J Mol Liq 238:379–388

    CAS  Google Scholar 

  • Negri V, Pacheco-Torres J, Calle D, López-Larrubia P (2020) Carbon nanotubes in biomedicine. Top Curr Chem (Cham) 378:15. https://doi.org/10.1007/s41061-019-0278-8

    Article  CAS  Google Scholar 

  • Nwankwo JO, Tahnteng JG, Emerole GO (2000) Inhibition of aflatoxin B1 genotoxicity in human liver-derived HepG2 cells by kolaviron biflavonoids and molecular mechanisms of action. Eur J Cancer Prev 9:351–361

    CAS  Google Scholar 

  • Olayinka ET, Ore A (2014) Kolaviron and L-ascorbic acid attenuate chlorambucil-induced testicular oxidative stress in rats. J Toxicol 2014:587015–587019. https://doi.org/10.1155/2014/587015

    Article  CAS  Google Scholar 

  • Patel DK, Kim HB, Dutta SD, Ganguly K, Lim KT (2020) Carbon nanotubes-based nanomaterials and their agricultural and biotechnological applications. Materials (Basel) 13(7):E1679. https://doi.org/10.3390/ma13071679

    Article  CAS  Google Scholar 

  • Patlolla AK, Berry A, Tchounwou PB (2011) Study of hepatotoxicity and oxidative stress in male Swiss-Webster mice exposed to functionalized multi-walled carbon nanotubes. Mol Cell Biochem 358(1–2):189–199

    CAS  Google Scholar 

  • Peruquetti RL, Taboga SR, Azeredo-Oliveira MT (2010) Expression of acid phosphatase in the seminiferous epithelium of vertebrates. Genet Mol Res 9:620–628

    CAS  Google Scholar 

  • Ralebona N, Sewani-Rusike CR, Nkeh-Chungag BN (2012) Effects of ethanolic extract of Garcinia kola on sexual behavior and sperm parameters in male Wistar rats. Afr J Pharm Pharmacol 6:1077–1082

    Google Scholar 

  • Rasras S, Kalantari H, Rezaei M, Dehghani MA, Zeidooni L, Alikarami K, Dehghani F, Alboghobeish S (2019) Single-walled and multiwalled carbon nanotubes induce oxidative stress in isolated rat brain mitochondria. Toxicol Ind Health 35:497–506

    CAS  Google Scholar 

  • Rode A, Sharma S, Mishra DK (2018) Carbon nanotubes: classification, method of preparation and pharmaceutical application. Curr Drug Deliv 15:620–629

    CAS  Google Scholar 

  • Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG (1973) Selenium: biochemical role as a component of glutathione peroxidase. Science 179:588–590

    CAS  Google Scholar 

  • Salihu M, Ajayi BO, Adedara IA, Farombi EO (2017) 6-Gingerol-rich fraction prevents disruption of histomorphometry and marker enzymes of testicular function in carbendazim-treated rats. Andrologia 49(10). https://doi.org/10.1111/and.12782

  • Sewani-Rusike CR, Ralebona N, Nkeh-Chungag BN (2016) Dose- and time-dependent effects of Garcinia kola seed extract on sexual behaviour and reproductive parameters in male Wistar rats. Andrologia. 48:300–307

    CAS  Google Scholar 

  • Shimada T, Nomura M, Yokogawa K, Endo Y, Sasaki T, Miyamoto K, Yonemura Y (2005) Pharmacokinetic advantage of intraperitoneal injection of docetaxel in the treatment for peritoneal dissemination of cancer in mice. J Pharm Pharmacol 57:177–181

    CAS  Google Scholar 

  • Vanha-Perttula T, Nikkanen V (1973) Acid phosphatases of the rat testis in experimental conditions. Acta Endocrinol 72:376–390

    CAS  Google Scholar 

  • Vassault A (1983) Lactate dehydrogenase. UV-method with pyruvate and NADH. In: Bergmeyer HU (ed) Methods of enzymatic analysis (3rd ed). Volume III. Plenum, New York, pp 118–125

    Google Scholar 

  • Wang R, Song B, Wu J, Zhang Y, Chen A, Shao L (2018) Potential adverse effects of nanoparticles on the reproductive system. Int J Nanomedicine 13:8487–8506

    CAS  Google Scholar 

  • Wells ME, Awa OA (1970) New technique for assessing acrosomal characteristics of spermatozoa. J Diary Sci 53:227–232

    CAS  Google Scholar 

  • World health organization (1999) Laboratory manual for the examination of human semen and sperm-cervical mucus interaction. 4th edn, vol 76. Cambridge University press, New York, pp 4–33

    Google Scholar 

  • Xu C, Liu Q, Liu H, Zhang C, Shao W, Gu A (2016) Toxicological assessment of multi-walled carbon nanotubes in vitro: potential mitochondria effects on male reproductive cells. Oncotarget. 7:39270–39278

    Google Scholar 

  • Zemjanis R (1970) Collection and evaluation of semen. In: Zemjanis R (ed) Diagnostic and therapeutic technique in animal reproduction, 2nd edn. William and Wilkins company, Waverly Press, Inc, Baltimore, pp 139–153

    Google Scholar 

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Correspondence to Ebenezer Olatunde Farombi.

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Adedara, I.A., Awogbindin, I.O., Maduako, I.C. et al. Kolaviron suppresses dysfunctional reproductive axis associated with multi-walled carbon nanotubes exposure in male rats. Environ Sci Pollut Res 28, 354–364 (2021). https://doi.org/10.1007/s11356-020-10324-y

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