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Platelet-rich plasma as a potential therapeutic approach against lead nitrate- and/or gamma radiation-induced hepatotoxicity

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A Correction to this article was published on 05 November 2018

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Abstract

Because of the potential regenerative and cytoprotective effects of its content of numerous bioactive growth factors and cytokines, platelet-rich plasma (PRP) became an attractive biomaterial for therapeutic purposes. Therefore, the current study was designed to investigate the potential therapeutic effect of PRP against lead nitrate- and/or γ-radiation-induced hepatotoxicity. To do so, hepatotoxicity was induced in rats by intraperitoneal administration of lead nitrate (7.5 mg/kg) thrice weekly for two consecutive weeks and/or a whole-body γ-irradiation at a single dose of 6 Gy. Activated PRP (0.5 ml/kg) was injected subcutaneously 24 h after the last dose of lead nitrate and/or γ-irradiation and continued twice weekly for three successive weeks. Lead nitrate intoxication and/or γ-irradiation resulted in a significant elevation of serum alanine transaminase and aspartate transaminase activities accompanied with a significant decrease in serum levels of total protein and albumin. Further, a significant increase in malondialdehyde level and nitric oxide content accompanied with a significant decrease in the reduced glutathione content and the enzyme activities of glutathione-S-transferase, superoxide dismutase, and catalase were observed. Additionally, hepatic extracellular signal-regulated kinase (ERK) and Akt signaling pathways were stimulated. PRP treatment notably ameliorated the induced cell injury, reduced the intracellular oxidative and interestingly increased the upregulation of phosphorylated ERK1/2 and Akt. Moreover, PRP treatment relieved lead nitrate and/or γ-radiation-induced hepatic histological damages. In conclusion, this study sheds the light on a probable therapeutic role of PRP against lead nitrate- and/or γ-radiation-induced hepatotoxicity which might attribute to its ability to activate ERK and Akt signaling pathways.

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Change history

  • 05 November 2018

    The original publication of this paper contains adjustment errors.

  • 11 April 2024

    Editor's Note: Readers are alerted that the concerns have been raised with this article. Editorial action will be taken as appropriate once this matter is resolved and all parties have been given an opportunity to respond in full.

References

  • Adanaylo VN, Oteiza PI (1999) Lead intoxication: antioxidant defenses and oxidative damage in rat brain. Toxicology 135:77–85

    Article  Google Scholar 

  • Alves R, Grimalt R (2016) Randomized placebo-controlled, double-blind, half-head study to assess the efficacy of platelet-rich plasma on the treatment of androgenetic alopecia. Dermatol Surg 42:491–497

    Article  CAS  Google Scholar 

  • Antebi U, Mathor MB, da Silva AF, Guimarães RP, Honda EK (2016) Effects of ionizing radiation on proteins in lyophilized or frozen demineralized human bone. Rev Bras Ortop 5:224–230

    Article  Google Scholar 

  • Bakacak M, Bostanci MS, İnanc F, Yaylali A, Serin S, Attar R, Yildirim G, Yildirim OK (2016) Protective effect of platelet rich plasma on experimental ischemia/reperfusion injury in rat ovary. Gynecol Obstet Investig 81:225–231

    Article  CAS  Google Scholar 

  • Beutler E, Duron O, Kelly B (1963) Improved method for the determination of blood glutathione. J Lab Clin Med 61:882–888

    CAS  Google Scholar 

  • Brzezianska E, Pastuszak-Lewandoska D (2011) A minireview: the role of MAPK/ERK and PI3K/Akt pathways in thyroid follicular cell-derived neoplasm. Front Biosci 16:422–439

    Article  CAS  Google Scholar 

  • Cantrell DA (2001) Phosphoinositide 3-kinase signalling pathways. J Cell Sci 114:1439–1445

    Article  CAS  Google Scholar 

  • Chang F, Lee JT, Navolanic PM, Steelman LS, Shelton JG, Blalock WL, Franklin RA, McCubrey JA (2003) Involvement of PI3K/Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation: a target for cancer chemotherapy. Leukemia 17:590–603

    Article  CAS  Google Scholar 

  • Chang L, Karin M (2001) Mammalian MAP kinase signalling cascades. Nature 410:37–40

    Article  CAS  Google Scholar 

  • Courtois E, Marques M, Barrientos A (2003) Lead-induced downregulation of soluble guanylate cyclase in isolated rat aortic segments mediated by reactive oxygen species and cyclooxygenase-2. J Am Soc Nephrol 14:1464–1470

    Article  CAS  Google Scholar 

  • Coutant A, Rescan C, Gilot D, Loyer P, Guguen-Guillouzo C, Baffet G (2002) PI3K-FRAP/mTOR pathway is critical for hepatocyte proliferation whereas MEK/ERK supports both proliferation and survival. Hepatology 36:1079–1088

    Article  CAS  Google Scholar 

  • Cromheecke M, Konings AW, Szabo BG, Hoekstra HJ (2000) Liver tissue tolerance for irradiation: experimental and clinical investigations. Hepatogastroenterology 47:1732–1740

    CAS  Google Scholar 

  • Cubero FJ, Trautwein C (2010) Oxidative stress and liver injury. In: Monga SPS (ed) Molecular pathology of liver diseases. Springer Science+Business Media, NY, USA, pp 427–435

    Google Scholar 

  • Cullinan SB, Diehl JA (2004) PERK-dependent activation of Nrf2 contributes to redox homeostasis and cell survival following endoplasmic reticulum stress. J Biol Chem 279:20108–20117

    Article  CAS  Google Scholar 

  • De Mos M, van der Windt AE, Jahr H, van Schie HT, Weinans H, Verhaar JA et al (2008) Can platelet-rich plasma enhance tendon repair? A cell culture study. Am J Sports Med 36:1171–1178

    Article  Google Scholar 

  • Einor D, Bonisoli-Alquati A, Costantini D, Mousseau TA, Møller AP (2016) Ionizing radiation, antioxidant response and oxidative damage: a meta-analysis. Sci Total Environ 548-549:463–471

    Article  CAS  Google Scholar 

  • Flora G, Gupta D, Tiwari A (2012) Toxicity of lead: a review with recent updates. Interdiscip Toxicol 5:47–58

    Article  CAS  Google Scholar 

  • Flora SJ, Pande M, Kannan GM, Mehta A (2004) Lead induced oxidative stress and its recovery following co-administration of merlatonin or N-acetylcysteine during chelation with succimer in male rats. Cell Mol Biol 50:OL543–OL551

    Google Scholar 

  • Franco D, Franco T, Schettino AM, Filho JM, Vendramin FS (2012) Protocol for obtaining platelet-rich plasma (PRP), platelet-poor plasma (PPP), and thrombin for autologous use. Aesthet Plast Surg 36:1254–1259

    Article  Google Scholar 

  • Franke TF, Hornik CP, Segev L, Shostak GA, Sugimoto C (2003) PI3K/Akt and apoptosis: size matters. Oncogene 22:8983–8998

    Article  CAS  Google Scholar 

  • Friedman SL (2008) Mechanisms of hepatic fibrogenesis. Gastroenterology 134:1655–1669

    Article  CAS  Google Scholar 

  • Gäbele E, Brenner DA, Rippe RA (2003) Liver fibrosis: signals leading to the amplification of the fibrogenic hepatic stellate cell. Front Biosci 8:d69–d77

    Article  Google Scholar 

  • García-Niño WR, Pedraza-Chaverrí J (2014) Protective effect of curcumin against heavy metals induced liver damage. Food Chem Toxicol 69:182–201

    Article  Google Scholar 

  • Guimaraes D, Carvalho ML, Geraldes V, Rocha I, Alves LC, Santos JP (2012) Lead in liver and kidney of exposed rats: aging accumulation study. J Trace Elem Med Biol 26:285–290

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Han PZ, Couvillon AD, Exton JH (2004) Critical role of endogenous Akt/IAPs and MEK1/ERK pathways in counteracting endoplasmic reticulum stress-induced cell death. J Biol Chem 279:49420–49429

    Article  Google Scholar 

  • Hemmann S, Graf J, Roderfeld M, Roeb E (2007) Expression of MMPs and TIMPs in liver fibrosis - a systematic review with special emphasis on anti-fibrotic strategies. J Hepatol 46:955–975

    Article  CAS  Google Scholar 

  • Hesami Z, Jamshidzadeh A, Ayatollahi M, Geramizadeh B, Farshad O, Vahdati A (2014) Effect of platelet-rich plasma on CCl4-induced chronic liver injury in male rats. Int J Hepatol 2014:932930

    Article  Google Scholar 

  • Hisakura K, Murata S, Fukunaga K, Myronovych A, Tadano S, Kawasaki T, Kohno K, Ikeda O, Pak S, Ikeda N, Nakano Y, Matsuo R, Konno K, Kobayashi E, Saito T, Yasue H, Ohkohchi N (2010) Platelets prevent acute liver damage after extended hepatectomy in pigs. J Hepatobiliary Pancreat Sci 17:855–864

    Article  Google Scholar 

  • Hwang YP, Jeong HG (2010) Ginsenoside Rb1 protects against 6-hydroxydopamine-induced oxidative stress by increasing heme oxygenase-1 expression through an estrogen receptor-related PI3K/Akt/Nrf2-dependent pathway in human dopaminergic cell. Toxicol Appl Pharmacol 242:18–28

    Article  CAS  Google Scholar 

  • Kim J, Yi NJ, Shin WY, Kim T, Lee KU, Suh KS (2010) Platelet transfusion can be related to liver regeneration after living donor liver transplantation. World J Surg 34:1052–1058

    Article  Google Scholar 

  • Kodama T, Takehara T, Hikita H, Shimizu S, Li W, Miyagi T et al (2010) Thrombocytopenia exacerbates cholestasis-induced liver fibrosis in mice. Gastroenterology 138:2487–2498 2498.e1-e7

    Article  CAS  Google Scholar 

  • Kregel KC, Zhang HJ (2007) An integrated view of oxidative stress in aging: basic mechanisms, functional effects, and pathological considerations. Am J Physiol Regul Integr Comp Physiol 292:R18–R36

    Article  CAS  Google Scholar 

  • Krishna A, Kumar A (2005) Evaluation of radioprotective effect of Rajira (Amaranthus paniculatus) extract in Swiss albino mice. J Rad Res 46:233–239. https://doi.org/10.1269/jrr.46.233

    Article  Google Scholar 

  • Lakshmi BV, Sudhakar M, Aparna M (2013) Protective potential of Black grapes against lead induced oxidative stress in rats. Environ Toxicol Pharmacol 35:361–368

    Article  CAS  Google Scholar 

  • Lang PA, Contaldo C, Georgiev P, El-Badry AM, Recher M, Kurrer M et al (2008) Aggravation of viral hepatitis by platelet-derived serotonin. Nat Med 14:756–761

    Article  CAS  Google Scholar 

  • Laschke MW, Dold S, Menger MD, Jeppsson B, Thorlacius H (2008) Platelet-dependent accumulation of leukocytes in sinusoids cholestasis. Br J Pharmacol 153:148–156

    Article  CAS  Google Scholar 

  • Le’on-Buitimea A, Rodr’ıguez-Fragoso L, Lauer FT, Bowles H, Thompson TA, Burchiel SW (2012) Ethanol-induced oxidative stress is associated with EGF receptor phosphorylation in MCF-10A cells overexpressing CYP2E1. Toxicol Lett 209:161–165

    Article  Google Scholar 

  • Lei H, Kazlauskas A (2009) Growth factors outside of the platelet-derived growth factor (PDGF) family employ reactive oxygen species/Src family kinases to activate PDGF receptor α and thereby promote proliferation and survival of cells. J Biol Chem 284:6329–6336

    Article  CAS  Google Scholar 

  • Leslie NR, Downes CP (2002) PTEN: the down side of PI3-kinase signalling. Cell Signal 14:285–295

    Article  CAS  Google Scholar 

  • Li ZJ, Choi HI, Choi DK, Sohn KC, Im M, Seo YJ, Lee YH, Lee JH, Lee Y (2012) Autologous platelet-rich plasma: a potential therapeutic tool for promoting hair growth. Dermatol Surg 38:1040–1046

    Article  CAS  Google Scholar 

  • Liu C, Ma J, Sun Y (2010) Quercetin protects the rat kidney against oxidative stress mediated DNA damage and apoptosis induced by lead. Environ Toxicol Pharmacol 30:264–271

    Article  CAS  Google Scholar 

  • Mansour HH (2006) Protective role of carnitine ester against radiation-induced oxidative stress in rats. Pharmacol Res 54:165–171

    Article  CAS  Google Scholar 

  • Martins RP, Hartmann DD, de Moraes JP, Soares FA, Puntel GO (2016) Platelet-rich plasma reduces the oxidative damage determined by a skeletal muscle contusion in rats. Platelets 27:784–790

    Article  CAS  Google Scholar 

  • Marx RE (2004) Platelet-rich plasma: evidence to support its use. J Oral Maxillofac Surg 62:489–496

    Article  Google Scholar 

  • Mauryaa DK, Adhikari S, Nair CKK, Devasagayam TPA (2007) DNA protective properties of vanillin against γ-radiation under different conditions: possible mechanisms. Mutat Res 634:69–80

    Article  Google Scholar 

  • McCubrey JA, Steelman LS, Abrams SL, Lee JT, Chang F, Bertrand FE et al (2006) Roles of the RAF/MEK/ERK and PI3K/PTEN/AKT pathways in malignant transformation and drug resistance. Adv Enzym Regul 46:249–279

    Article  CAS  Google Scholar 

  • Miranda KM, Espey MG, Wink DA (2001) A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 5:62–71

    Article  CAS  Google Scholar 

  • Mudipalli A (2007) Lead hepatotoxicity and potential health effects. Indian J Med Res 126:518–527

    CAS  Google Scholar 

  • Murata S, Hashimoto I, Nakano Y, Ikeda O, Aoyagi Y, Matsuo R et al (2009) Platelets contribute to the reduction of liver fibrosis in mice. J Gastroenterol Hepatol 24:78–89

    Article  Google Scholar 

  • Murata S, Takahashi K, Nozaki R, Ohshiro Y, Ikeda N, Pak S et al (2010) Activation of human liver sinusoidal endothelial cell by human platelets induces hepatocyte proliferation. J Hepatol 53:648–654

    Article  Google Scholar 

  • Myronovych A, Murata S, Chiba M, Matsuo R, Ikeda O, Watanabe M, Hisakura K, Nakano Y, Kohno K, Kawasaki T, Hashimoto I, Shibasaki Y, Yasue H, Ohkohchi N (2008) Role of platelets on liver regeneration after 90% hepatectomy in mice. J Hepatol 49:363–372

    Article  CAS  Google Scholar 

  • Nakano Y, Kondo T, Matsuo R, Hashimoto I, Kawasaki T, Kohno K, Myronovych A, Tadano S, Hisakura K, Ikeda O, Watanabe M, Murata S, Fukunaga K, Ohkohchi N (2008) Platelet dynamics in the early phase of postischemic liver in vivo. J Surg Res 149:192–198

    Article  CAS  Google Scholar 

  • Osburn WO, Kensler TW (2008) Nrf2 signaling: an adaptive response pathway for protection against environmental toxic insults. Mutat Res 659:31–39

    Article  CAS  Google Scholar 

  • Pak S, Kondo T, Nakano Y, Murata S, Fukunaga K, Oda T et al (2010) Platelet adhesion in the sinusoid caused hepatic injury by neutrophils after hepatic ischemia reperfusion. Platelets 21:282–288

    Article  CAS  Google Scholar 

  • Plotnikov A, Zehorai E, Procaccia S, Seger R (2011) The MAPK cascades: signaling components, nuclear roles and mechanisms of nuclear translocation. Biochimica et Biophysica Acta-Molecular Cell Res 1813:1619–1633

    Article  CAS  Google Scholar 

  • Reyes JL, Molina-Jijon E, Rodriguez-Munoz R, Bautista-Garcia P, Debray-Garcia Y, Namorado Mdel C (2013) Tight junction proteins and oxidative stress in heavy metals-induced nephrotoxicity. Biomed Res Int 2013:730789

    Article  Google Scholar 

  • Rosseland CM, Wierod L, Oksvold MP, Werner H, Ostvold AC, Thoresen GH et al (2005) Cytoplasmic retention of peroxide-activated ERK provides survival in primary cultures of rat hepatocytes. Hepatology 42:200–207

    Article  CAS  Google Scholar 

  • Saïdi S, Azaza M, Windmolders P, van Pelt J, El-Feki A (2013) Cytotoxicity evaluation and antioxidant enzyme expression related to heavy metals found in tuna by-products meal: an in vitro study in human and rat liver cell lines. Exp Toxicol Pathol 65:1025–1033

    Article  Google Scholar 

  • Sánchez-González DJ, Méndez-Bolaina E, Trejo-Bahena NI (2012) Platelet-rich plasma peptides: key for regeneration. Int J Pept 2012:532519

    Article  Google Scholar 

  • Sato M, Harasaki H (2002) Evaluation of platelet and coagulation function in different animal species using the xylum clot signature analyzer. ASAIO J 48:360–364

    Article  CAS  Google Scholar 

  • Shahid S, Masood K (2018) Assessing liver proteins and enzymes of medical workers exposed to ionizing radiation (IR). Clin Exp Med 18:89–99

    Article  CAS  Google Scholar 

  • Shalan MG, Mostafa MS, Hassouna MM, El-Nabi SE, El-Refaie A (2005) Amelioration of lead toxicity on rat liver with vitamin C and silymarin supplements. Toxicology 206:1–15

    Article  CAS  Google Scholar 

  • Sinha AK (1972) Colorimetric assay of catalase. Anal Biochem 47:389–394

    Article  CAS  Google Scholar 

  • Spitz DR, Azzam EI, Li JJ, Gius D (2004) Metabolic oxidation reduction reaction and cellular responses to ionizing radiation: a unifying concept in stress response biology. Cancer Metast Rev 23:311–322

    Article  CAS  Google Scholar 

  • Srinivasan MN, Basu SK, Shose A (1985) Effect of chemical radioprotectors on serum proteins of rats exposed to gamma irradiation. Ind J Exp Biol 23:490–492

    CAS  Google Scholar 

  • Suzuki K, Kodama S, Watanabe M (2001) Extremely low-dose ionizing radiation causes activation of mitogen-activated protein kinase pathway and enhances proliferation of normal human diploid cells. Cancer Res 61:5396–5401

    CAS  Google Scholar 

  • Tohidnezhand M, Wruck CJ, Slowik A, Kweider N, Beckmann R, Bayer A et al (2014) Role of platelet-released growth factors in detoxification of reactive oxygen species in osteoblasts. Bone 65:9–17

    Article  Google Scholar 

  • Tokara EJ, Diwanc BA, Waalkes MP (2010) Early life inorganic lead exposure induces testicular teratoma and renal and urinary bladder preneoplasia in adult metallothionein-knockout mice but not in wild type mice. Toxicology 276:5–10

    Article  Google Scholar 

  • Valverde M, Trejo C, Rojas E (2001) Is the capacity of lead acetate and cadmium chloride to induce genotoxic damage due to direct DNA–metal interaction? Mutagenesis 16:265–270

    Article  CAS  Google Scholar 

  • Weibrich G, Kleis WK, Hafner G, Hitzler WE (2002) Growth factor levels in platelet-rich plasma and correlations with donor age, sex, and platelet count. J Craniomaxillofac Surg 30:97–102

    Article  Google Scholar 

  • Xiang JJ, Zhai YF, Tang Y, Wang H, Liu B, Guo CW (2010) A competitive indirect enzyme-linked immunoassay for lead ion measurement using mAbs against the lead–DTPA complex. Environ Pollut 158:1376–1380

    Article  CAS  Google Scholar 

  • Yao P, Nussler A, Liu L, Hao L, Song F, Schirmeier A, Nussler N (2007) Quercetin protects human hepatocytes from ethanol-derived oxidative stress by inducing heme oxygenase-1 via the MAPK/Nrf2 pathways. J Hepatol 47:253–261

    Article  CAS  Google Scholar 

  • Yoshioka T, Kawada K, Shimada T, Mori M (1979) Lipid peroxidation in maternal and cord blood and protective mechanism against activated- oxygen toxicity in the blood. Am J Obstet Gynecol 135:372–376

    Article  CAS  Google Scholar 

  • Zaldivar MM, Pauels K, von Hundelshausen P, Berres ML, Schmitz P, Bornemann J, Kowalska MA, Gassler N, Streetz KL, Weiskirchen R, Trautwein C, Weber C, Wasmuth HE (2010) CXC chemokine ligand 4 (Cxcl4) is a platelet-derived mediator of experimental liver fibrosis. Hepatology 51:1345–1353

    Article  CAS  Google Scholar 

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Acknowledgements

We thank Adel B. Kholoussy at the Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Egypt for his assistance in examining and interpreting the histopathology aspects of this work.

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Authors and Affiliations

  1. Drug Radiation Research Department, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Egypt

    Salma M. Abdel Fattah

  2. Health Radiation Research Department, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Egypt

    Mostafa Saif-Elnasr

  3. Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt

    Ahmed F. Soliman

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  1. Salma M. Abdel Fattah
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  2. Mostafa Saif-Elnasr
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Correspondence to Salma M. Abdel Fattah.

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Responsible editor: Philippe Garrigues

The original version of this article was revised: The original publication of this paper contains adjustment errors. The images for figures 1 and 2 were adjusted and shown in the original paper.

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Abdel Fattah, S.M., Saif-Elnasr, M. & Soliman, A.F. Platelet-rich plasma as a potential therapeutic approach against lead nitrate- and/or gamma radiation-induced hepatotoxicity. Environ Sci Pollut Res 25, 34460–34471 (2018). https://doi.org/10.1007/s11356-018-3366-3

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