Abstract
In this study, the protective effects of Ginkgo biloba leaf extract (GbE) against toxicity induced by hydrogen peroxide (H2O2) in Swiss albino mice were investigated. Abnormal metaphase number (AMn), mitotic index (MI), micronucleus (MN), and chromosomal abnormalities (CAs) were analyzed for cytogenetic effects. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), blood urea nitrogen (BUN), creatinine, glutathione (GSH), and malondialdehyde (MDA) levels in liver and kidney organs were investigated as indicators of biochemical toxicity. Six experimental groups were formed as a control and treatment group, each containing six animals. The mice in the control group were given tap water, while the mice in the administration group received two different doses of GbE and H2O2 for 45 consecutive days. It was observed that H2O2 administration caused a significant decrease in MI compared to the control group and caused a significant decrease in the frequency of AMn, MN, and CAs. Chromatid break was the most common type of CAs induced by H2O2, and the other CAs types observed in this study were chromosome break, fragment, dicentric, gap, and ring. It has been determined that GbE treatment decreases the clastogenic effects of H2O2 and reduces the MN and CAs frequency and causes a re-increase in mitotic cell numbers. It was determined that H2O2 administration caused changes in biochemical parameters and resulted in significant increases in serum AST, ALP, ALT, BUN, and creatinine levels. However, the level of MDA, which is an indicator of oxidative damage, increased, and GSH level decreased in liver and kidney tissues. Oxidative damage caused by H2O2 in liver and kidney tissues was improved, and all biochemical parameters tested were found to be ameliorated after GbE treatment. This improvement was dependent on the dose of GbE, and improvement in 150 mg/kg bw GbE was found to be more prominent. As a result, the GbE can be used as an antioxidant nutritional supplement to protect against the toxic effects of environmental agents such as H2O2.
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References
Abdul-Hamid M, Galaly SR, Mahmoud H, Mostafa F (2018) The protective effect of grape seed and Ginkgo biloba against hepatotoxicity induced by the antidysrhythmic drug “amiodarone” in male albino rats. Beni-Seuf Univ J Appl Sci 7:223–230. https://doi.org/10.1016/j.bjbas.2017.12.001
Abed TS, Ismael SH, Abdulnabi H (2015) Multiple protective effects of Ginkgo biloba against hepatic and cardiac toxicity induced by cisplatin in rats. Pharmacie Globale 6:1–6
Beutler E, Duran O, Kelley BM (1963) Improved method for determination of blood glutathione. J Lab Clin Med 28:882–888
Bridi R, Crossetti FP, Steffen VM, Henriques AT (2001) The antioxidant activity of standardized extract of Ginkgo biloba (EGb 761) in rats. Phytother Res 15:449–451
Brooks JE, Rowe FP (1987) Rodents: training and information guide (no. WHO/VBC/87.949). World Health Organization, Geneva
Cavusoglu K, Yapar K, Yalçın E (2009) The royal jelly (honey bee) has a potential antioxidant against cadmium-induced genotoxicity and oxidative stress in albino mice. J Med Food 12:1286–1292. https://doi.org/10.1089/jmf.2008.0203
Celik I, Cihangiroglu M, Ilhan N, Akpolat N, Akbulut HH (2005) Protective effects of different antioxidants and amrinone on vancomycin-induced nephrotoxicity. Basic Clin Pharmacol Toxicol 97:325–332. https://doi.org/10.1111/j.1742-7843.2005.pto_153.x
Chandrasekaran K, Mehrabian Z, Spinnewyn B, Chinopoulos C, Drieu K, Fiskum G (2002) Bilobalide, a component of the Ginkgo biloba extract (EGb 761), protects against neuronal death in global brain ischemia and in glutamate-induced excitotoxicity. Cell Mol Biol 48:663–669
Chang YH, Chen YG, Yang GY (2011) Effects of Ginkgo biloba extract on the expression of eNOS and the release of NO in mesenteric arterioles of senile rats. Zhonghua Yi Xue Za Zhi 91:2501–2505
Cholbi MR, Paya M, Alcaraz MJ (1991) Inhibitory effects of phenolic compounds on CCl4-induced microsomal lipid peroxidation. Experientia 47:195–199
Christen Y (2004) Ginkgo biloba and neurodegenerative disorders. Front Biosci 9:3091–3104. https://doi.org/10.2741/1462
Clarkson MR, Brenner BM, Magee C (2011) Clinical assessment of the patient with kidney disease. In: Pocket companion to brenner and rector's the kidney. Elsevier, Saunders, pp 3–20. https://doi.org/10.1016/B978-1-4160-6640-8.00001-4
El-Maksoud EMA, Lebda MA, Hashem AE, Taha NM, Kamel MA (2019) Ginkgo biloba mitigates silver nanoparticles-induced hepatotoxicity in Wistar rats via improvement of mitochondrial biogenesis and antioxidant status. Environ Sci Pollut Res 26:25844–25854. https://doi.org/10.1007/s11356-019-05835-2
El-Shenawy SM, Hassan NS (2008) Comparative evaluation of the protective effect of selenium and garlic against liver and kidney damage induced by mercury chloride in the rats. Pharmacol Rep 60:199–208
Ganie SA, Haq E, Hamid A, Masood A, Zargar MA (2011) Long dose exposure of hydrogen peroxide (H2O2) in albino rats and effect of Podophyllum hexandrum on oxidative stress. Eur Rev Med Pharmacol Sci 15:906–915
Guan R, ZhaoY, Zhang H, Fan G, Liu X, Zhou W et al (2016) Draft genome of the living fossil Ginkgo biloba. Gigascience 5:49–62. https://doi.org/10.1186/s13742-016-0154-1
Guidetti C, Paracchini S, Lucchini S, Cambieri M, Marzatico F (2001) Prevention of neuronal cell damage induced by oxidative stress in-vitro: effect of different Ginkgo biloba extracts. J Pharm Pharmacol 53:387–392. https://doi.org/10.1211/0022357011775442
He YT, Xing SS, Gao L, Wang J, Xing QC, Zhang W (2014) Ginkgo biloba attenuates oxidative DNA damage of human umbilical vein endothelial cells induced by intermittent high glucose. Pharmazie 69:203–207
Hsu JY, Chu JJ, Chou MC, Chen YW (2013) Dioscorin pre-treatment protects A549 human airway epithelial cells from hydrogen peroxide-induced oxidative stress. Inflammation 36:1013–1019. https://doi.org/10.1007/s10753-013-9633-z
Hyder MA, Hasan M, Mohieldein AH (2013) Comparative levels of ALT, AST, ALP and GGT in liver associated diseases. Euro J Exp Bio 3:280–284
Li M, Zhao L, Liu J, Liu AL, Zeng WS, Luo SQ, Bai XC (2009) Hydrogen peroxide induces G2 cell cycle arrest and inhibits cell proliferation in osteoblasts. Anat Rec 292:1107–1113. https://doi.org/10.1002/ar.20925
Lin SY, Chang HP (1997) Induction of superoxide dismutase and catalase activity in different rat tissues and protection from UVB irradiation after topical application of Ginkgo biloba extracts. Methods Find Exp Clin Pharmacol 19:367–371
Ma S, Liu H, Jiao H, Wang L, Chen L, Liang J, Zhao M, Zhang X (2012) Neuroprotective effect of ginkgolide K on glutamate-induced cytotoxicity in PC 12 cells via inhibition of ROS generation and Ca2+ influx. Neurotoxicology 33:59–69. https://doi.org/10.1016/j.neuro.2011.11.003
Mahaseth T, Kuzminov A (2017) Potentiation of hydrogen peroxide toxicity: from catalase inhibition to stable DNA-iron complexes. Mutat Res 773:274–281. https://doi.org/10.1016/j.mrrev.2016.08.006
Mahesh T, Menon VP (2004) Quercetin allievates oxidative stress in streptozotocin-induced diabetic rats. Phytother Res 18:123–127. https://doi.org/10.1002/ptr.1374
Marques F, Azevedo F, Johansson B, Oliveira R (2011) Stimulation of DNA repair in Saccharomyces cerevisiae by Ginkgo biloba leaf extract. Food Chem Toxicol 49:1361–1366. https://doi.org/10.1016/j.fct.2011.03.020
Naz S, Irshad F, Mawani H (2017) CCl4 induced liver injury; aqueous extract of Ginkgo biloba (gkbe) ameliorates cytoplasmic and mitochondrial enzymes. Professional Med J 24:739–744. https://doi.org/10.17957/TPMJ/17.3762
Parimoo HA, Sharma R, Patil RD, Sharma OP, Kumar P, Kumar N (2014) Hepatoprotective effect of Ginkgo biloba leaf extract on lantadenes-induced hepatotoxicity in guinea pigs. Toxicon 81:1–12. https://doi.org/10.1016/j.toxicon.2014.01.013
Riley MV, Giblin FJ (1982) Toxic effects of hydrogen peroxide on corneal endothelium. Curr Eye Res 2:451–458. https://doi.org/10.3109/02713688208996348
Romeo C, Eaton S, Quant PA, Spitz L, Pierro A (1999) Neonatal oxidative liver metabolism: effects of hydrogen peroxide, a putative mediator of spetic damage. J Pediatr Surg 34:1107–1111. https://doi.org/10.1016/S0022-3468(99)90577-8
Salahudeen AK, Clark EC, Nath KA (1991) Hydrogen peroxide-induced renal injury. A protective role for pyruvate in vitro and in vivo. J Clin Invest 88:1886–1893. https://doi.org/10.1172/JCI115511
Santoro A, Lioi MB, Monfregola J, Salzano S, Barbieri R, Ursini MV (2005) L-carnitine protects mammalian cells from chromosome aberrations but not from inhibition of cell proliferation induced by hydrogen peroxide. Mutat Res 587:16–25. https://doi.org/10.1016/j.mrgentox.2005.07.005
Savage JR (1976) Classification and relationships of induced chromosomal structural changes. J Med Genet 13:103–122. https://doi.org/10.1136/jmg.13.2.103
Sharma Y, Bashir S, Rshad M, Gupta SD, Dogra TD (2005) Effects of acute dimethoate administration on antioxidant status of liver and brain of experimental rats. Toxicology 206:49–57. https://doi.org/10.1016/j.tox.2004.06.062
Singh B, Kaur P, Singh RD, Ahuja PS (2008) Biology and chemistry of Ginkgo biloba. Fitoterapia 79:401–418. https://doi.org/10.1016/j.fitote.2008.05.007
Singh SK, Srivastav S, Castellani RJ, Plascencia-Villa G, Perry G (2019) Neuroprotective and antioxidant effect of Ginkgo biloba extract against AD and other neurological disorders. Neurotherapeutics 16:666–674. https://doi.org/10.1007/s13311-019-00767-8
Te-Hsiu MA, Zhou X, Loarco GF, Arreola GG, Lecona SU (1995) Mouse–erythrocyte micronucleus (Mus-EMN) assay on the clastogenicity of industrial wastewater. Rev Int Contam Ambient 11:95–98
Titenko-Holland N, Windham G, Kolachana P, Reinisch F, Parvatham S, Osorio AM, Smith MT (1997) Genotoxicity of malathion in human lymphocytes assessed using the micronucleus assay in vitro and in vivo: a study of malathion-exposed workers. Mutat Res 388:85–95. https://doi.org/10.1016/S1383-5718(96)00140-4
Tosaki A, Engelman DT, Pali T, Engelman RM, Droy-Lefaix MT (1994) Ginkgo biloba extract (EGb 761) improves postischemic function in isolated preconditioned working rat hearts. Coron Artery Dis 5:443–450. https://doi.org/10.1097/00019501-199405000-00011
Wagner C, Fachinetto R, Dalla Corte CL, Brito VB, Severo D, Dias GDOC et al (2006) Quercitrin, a glycoside form of quercetin, prevents lipid peroxidation in vitro. Brain Res 1107(1):192–198. https://doi.org/10.1016/j.brainres.2006.05.084
Wahby MM, Abdallah ZM, Abdou HM, Yousef MI, Newairy ASA (2017) Mitigating potential of Ginkgo biloba extract and melatonin against hepatic and nephrotoxicity induced by bisphenol a in male rats. Egyptian J Basic Appl Sci 4:350–357. https://doi.org/10.1016/j.ejbas.2017.04.004
Wiles M, Williams J, Ahmad K (2010) Essentials of dermatology for chiropractors. Minnesota, Bloomington, pp 160–161
Wu WR, Zhu XZ (1999) Involvement of monoamine oxidase inhibition in neuroprotective and neurorestorative effects of Ginkgo biloba extract against MPTP-induced nigrostriatal dopaminergic toxicity in C57 mice. Life Sci 65:157–164. https://doi.org/10.1016/S0024-3205(99)00232-5
Xue Y, Daniels LB, Maisel AS, Iqbal N (2014) Cardiac biomarkers. In: Reference Module in Biomedical Sciences , Elsevier. https://doi.org/10.1016/B978-0-12-801238-3.00022-2
Yoshioka T, Kawada K, Shimada T (1979) Lipid peroxidation in maternal and cord blood and protective mechanism against active-oxygen toxicity in the blood. Am J Obstet Gynecol 135:372–376. https://doi.org/10.1016/0002-9378(79)90708-7
Zhu G, Wang Q, Lu S, Niu Y (2017) Hydrogen peroxide: a potential wound therapeutic target. Med Princ Pract 26:301–308. https://doi.org/10.1159/000475501
Zunino A, Degan P, Vigo T, Abbondandolo A (2001) Hydrogen peroxide: effects on DNA, chromosomes, cell cycle and apoptosis induction in Fanconi's anemia cell lines. Mutagenesis 16:283–288. https://doi.org/10.1093/mutage/16.3.283
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This study is supported by Giresun University Scientific Research Projects Department (FEN-BAP-A-140411-26).
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Yalçın, E., Çavuşoğlu, K., Acar, A. et al. In vivo protective effects of Ginkgo biloba L. leaf extract against hydrogen peroxide toxicity: cytogenetic and biochemical evaluation. Environ Sci Pollut Res 27, 3156–3164 (2020). https://doi.org/10.1007/s11356-019-07156-w
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DOI: https://doi.org/10.1007/s11356-019-07156-w