Platelet-rich plasma as a potential therapeutic approach against lead nitrate- and/or gamma radiation-induced hepatotoxicity
- 259 Downloads
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.
KeywordsPlatelet-rich plasma (PRP) Lead nitrate Gamma radiation Hepatotoxicity Oxidative stress Extracellular signal-regulated kinase (ERK) Akt
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.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Beutler E, Duron O, Kelly B (1963) Improved method for the determination of blood glutathione. J Lab Clin Med 61:882–888Google Scholar
- Cantrell DA (2001) Phosphoinositide 3-kinase signalling pathways. J Cell Sci 114:1439–1445Google Scholar
- Cromheecke M, Konings AW, Szabo BG, Hoekstra HJ (2000) Liver tissue tolerance for irradiation: experimental and clinical investigations. Hepatogastroenterology 47:1732–1740Google 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 427–435Google 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–OL551Google Scholar
- Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione S-transferases: the first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130–7139Google 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 17:855–864CrossRefGoogle Scholar
- Mudipalli A (2007) Lead hepatotoxicity and potential health effects. Indian J Med Res 126:518–527Google 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 23:490–492Google 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 61:5396–5401Google 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 51:1345–1353CrossRefGoogle Scholar