RESEARCH PAPER
Protective effects of molecular hydrogen on hepatotoxicity induced by sub-chronic exposure to chlorpyrifos in rats
,
 
,
 
,
 
,
 
,
 
,
 
,
 
 
 
More details
Hide details
1
Chao-Yang Hospital, Capital Medical University, Beijing, China
 
2
College of Life Science and Bioengineering, University of Technology, Beijing, China
 
3
Commission for Science and Technology, Miyun District, Beijing, China
 
 
Corresponding author
Xiao-yang Li   

Beijing Chao-Yang Hospital, Capital Medical University, China
 
 
Ann Agric Environ Med. 2020;27(3):368-373
 
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Chlorpyrifos (CPF) is a organophosphate insecticide widely used in agriculture with attendant adverse health outcomes. Chronic exposure to CPF induces oxidative stress and elicits harmful effects, including hepatic dysfunction. Molecular hydrogen has been identified as a novel antioxidant which could selectively scavenge hydroxyl radicals.

Objective:
The aim of this study was to determine whether the intake of hydrogen-rich water (HRW) could protect rats from hepatotoxicity caused by sub-chronic exposure to CPF.

Material and methods:
Rats were treated with hydrogen-rich water by oral intake for 8 weeks. Biochemical indicators of liver function, SOD and CAT activity, GSH and MDA levels were determined by the spectrophotometric method. Liver cell damage induced by CPF was evaluated by histopathological and electron microscopy analysis. PCR array analysis was performed to investigated the effects of molecular hydrogen on the regulation of oxidative stress related genes.

Results:
Both the hepatic function tests and histopathological analysis showed that the liver damage induced by CPF could be ameliorated by HRW intake. HRW intake also attenuated CPF induced oxidative stress, as evidenced by restored SOD activities and MDA levels. The results of PCR Array identified 12 oxidative stress-related genes differentially expressed after CPF exposure, 8 of chich, including the mitochondrial Sod2 gene, were significantly attenuated by HRW intake. The electron microscopy results indicated that the mitochondrial damage caused by CPF was alleviated after HRW treatment.

Conclusions:
The results obtained suggest that HRW intake can protect rats from CPF induced hepatotoxicity, and the oxidative stress signaling and the mitochondrial pathway may be involved in the protection of molecular hydrogen.

 
REFERENCES (30)
1.
Costa LG. Current issues in organophosphate toxicology. Clinica Chimica Acta. 2006; 366(1–2): 1–13.
 
2.
Murray A, Rathbone AJ, Ray DE. Novel protein targets for organo-phosphorus pesticides in rat brain. Environ Toxicol Pharmacol. 2005; 19(3): 451–454.
 
3.
Betancourt AM, Carr R L. The effect of chlorpyrifos and chlorpyrifos-oxon on brain cholinesterase, muscarinic receptor binding, and neurotrophin levels in rats following early postnatal exposure. Toxicoll Sci. 2004; 77(1): 63–71.
 
4.
Mehta A, Verma RS, Srivas N. Chlorpyrifos induced alterations in the levels of hydrogen peroxide, nitrate and nitrite in rat brain and liver. Pesticide Biochem Physiol. 2009; 94(2–3): 55–59.
 
5.
Uchendu C, Ambali SF, Ayo JO. The organophosphate, chlorpyrifos, oxidative stress and the role of some antioxidants: a review. African J Agric Res. 2012; 7(18): 2720–2728.
 
6.
Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K, et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nature Med. 2007; 13(6): 688–694.
 
7.
Fukuda KI, Asoh S, Ishikawa M, Yamamoto Y, Ohsawa I, Ohta S. Inhalation of hydrogen gas suppresses hepatic injury caused by ischemia/reperfusion through reducing oxidative stress. Biochem Biophysic Res Communic. 2007; 361(3): 670–674.
 
8.
Ohsawa I, Nishimaki K, Yamagata K, Ishikawa M, Ohta S. Consumption of hydrogen water prevents atherosclerosis in apolipoprotein E knockout mice. Biochem Biophysic Res Communic. 2008; 377(4): 1195–1198.
 
9.
Kajiyama S, Hasegawa G, Asano M, Hosoda H, Fukui M, Nakamura N, et al. Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance. Nutr Res. 2008; 28(3): 137–143.
 
10.
Nakao A, Toyoda Y, Sharma P, Evans M, Guthrie N. Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome-an open label pilot study. J Clin Biochem Nutr. 2010; 46(2): 140–149.
 
11.
Fu Y, Ito M, Fujita Y, et al. Molecular hydrogen is protective against 6-hydroxydopamine-induced nigrostriatal degeneration in a rat model of Parkinson’s disease. Neurosci Lett. 2009; 453(2): 81–85.
 
12.
Wang TT, Zhao L, Liu MY, Xie F, Mei XM, et al. Oral intake of hydrogen-rich water ameliorated chlorpyrifos-induced neurotoxicity in rats. Toxicol Applied Pharmacol. 2014; 280(1): 169–176.
 
13.
Goth L. A simple method for determination of serum catalase activity and revision of reference range. Clinica Chimica Acta 1991; 196(2–3): 143–151.
 
14.
Eaton DL, Daroff RB, Autrup H, Bridges J, Buffler P, Costa LG, et al. Review of the toxicology of chlorpyrifos with an emphasis on human exposure and neuro-development. Critical Rev Toxicol. 2008; 38(1): 1–125.
 
15.
Mansour SA, Mossa ATH. Oxidative damage, biochemical and histopathological alterations in rats exposed to chlorpyrifos and the antioxidant role of zinc. Pesticide Biochem Physiol. 2010; 96(1): 14–23.
 
16.
Raina R, Baba NA, Verma PK, Sultana M, Singh M. Hepatotoxicity induced by subchronic exposure of fluoride and chlorpyrifos in wistar rats: mitigating effect of ascorbic acid. Biol Trace Element Res. 2015; 166(2): 157–162.
 
17.
Khan SM, Sobti RC, Kataria L. Pesticide-induced alteration in mice hepato-oxidative status and protective effects of black tea extract. Clinica Chimica Acta. 2005; 358(1–2): 131–138.
 
18.
Abdollahi M, Ranjbar A, Shadnia S, Nikfar S, Rezaie A. Pesticides and oxidative stress: a review. Med Sci Monitor. 2004; 10(6): 141–147.
 
19.
Bebe FN, Panemangalore M. Exposure to low doses of endosulfan and chlorpyrifos modifies endogenous antioxidants in tissues of rats. J Environ Sci Health Part B 2003; 38(3): 349–363.
 
20.
Zelko IN, Mariani TJ, Folz RJ. Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression. Free Radical Biol Med. 2002; 33(3): 337–349.
 
21.
Cui Y, Zhang H, Ji M, Jia M, et al. Hydrogen-rich saline attenuates neuronal ischemia-reperfusion injury by protecting mitochondrial function in rats. J Surg Res. 2014; 192(2): 564–572.
 
22.
Yoshida A, Asanuma H, Sasaki H, Sanda S, Yamazaki S, Asano Y, et al. H(2) mediates cardioprotection via involvements of k(atp) channels and permeability transition pores of mitochondria in dogs. Cardiovasc Drugs Ther. 2012; 26(3): 217–226.
 
23.
Tarmure S, Alexescu TG, Orasan O, Negrean V, Sitar-Taut AV, Coste SC, et al. Influence of pesticides on respiratory pathology-a literature review. Ann Agric Environ Med. 2020; 27(2): 194–200.
 
24.
Sak ZHA, Kurtuluş Ş, Ocakli B, Töreyin ZN, Bayhan I, Yeşilnacar MI, et al. Respiratory symptoms and pulmonary functions before and after pesticide application in cotton farming. Ann Agric Environ Med. 2018; 25(4): 701–707.
 
25.
Huang P, Wei S, Huang W, Wu P, Chen S, Tao A, et al. Hydrogen gas inhalation enhances alveolar macrophage phagocytosis in an ovalbumin-induced asthma model. Int Immunopharmacol. 2019; 74(105646): 1–10.
 
26.
Liu X, Ma C, Wang X, Wang W, Li Z, Wang X, et al. Hydrogen coadministration slows the development of COPD-like lung disease in a cigarette smoke-induced rat model. Int J Chron Obstruct Pulmon Dis. 2017; 12: 1309–1324.
 
27.
Liu Z, Geng W, Jiang C, Zhao S, Liu Y, Zhang Y, et al. Hydrogen-rich saline inhibits tobacco smoke-induced chronic obstructive pulmonary disease by alleviating airway inflammation and mucus hypersecretion in rats. Exp Biol Med. 2017; 242(15): 1534–1541.
 
28.
Lu W, Li D, Hu J, Mei H, Shu J, Long Z, et al. Hydrogen gas inhalation protects against cigarette smoke-induced COPD development in mice. J Thorac Dis. 2018; 10(6): 3232–3243.
 
29.
Wang D, Wang L, Zhang Y, Zhao Y, Chen G. Hydrogen gas inhibits lung cancer progression through targeting SMC3. Biomed Pharmacother. 2018; 104: 788–797.
 
30.
Chen J, Kong X, Mu F, Lu T, Lu Y, Xu K. Hydrogen therapy can be used to control tumor progression and alleviate the adverse events of medications in patients with advanced non-small cell lung cancer. Med Gas Res. 2020; 10(2): 75–80.
 
eISSN:1898-2263
ISSN:1232-1966
Journals System - logo
Scroll to top