Abstract
Malathion is a potent organophosphate insecticide that inhibits acetylcholinesterase (AChE) enzyme. Our experimental objective was to investigate the beneficial effects of diallyl sulphide (DAS) and thymoquinone (TQ) against malathion-induced oxidative stress in rat cerebral, hepatic, and renal tissues. For 30 days, rats received corn oil alone (negative control) or malathion by intragastric gavage (200 mg/kg daily), either alone (positive control) or combined with oral DAS (200 mg/kg daily) or TQ (10 mg/kg daily) (treatment groups). Later, blood samples were collected via direct cardiac puncture and tissue samples were obtained for biochemical analysis. Malathion administration was associated with significant increases (p < 0.05) in the serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, γ-glutamyl transferase, cholesterol, urea, creatinine, and 8-OHdG (DNA damage biomarker), as well as significant (p < 0.05) decreases in the serum levels of total proteins, albumin, triglycerides, and AChE. Moreover, it significantly increased the tissue concentrations of malondialdehyde and nitric oxide and reduced tissue glutathione concentration and activities of antioxidant enzymes (glutathione peroxidase, superoxide dismutase, and catalase). Treatment of malathion-intoxicated rats with DAS or TQ significantly minimized these biochemical and oxidative effects with more frequent reversal to normal ranges of serum biomarkers, tissue oxidative markers, and antioxidant enzymes in the TQ group. In conclusion, treatment with DAS or TQ ameliorated the biochemical and oxidative effects of malathion, probably through reducing the generation of reactive oxygen and nitrogen radicals, as well as enhancing the antioxidant defense mechanisms.
Similar content being viewed by others
Abbreviations
- AChE:
-
Acetylcholine esterase
- ALT:
-
Alanine aminotransferase
- ALP:
-
Alkaline phosphatase
- AST:
-
Aspartate aminotransferase
- CAT:
-
Catalase
- DAS:
-
Diallyl sulphide
- γ-GT:
-
Gamma-glutamyl transferase
- GSH:
-
Glutathione
- GPx:
-
Glutathione peroxidase
- LDH:
-
Lactate dehydrogenase
- MDA:
-
Malondialdehyde
- NO:
-
Nitric oxide
- 8-OHdG:
-
8-Hydroxy-2′-deoxyguanosine
- OP:
-
Organophosphate
- SOD:
-
Superoxide dismutase
- TQ:
-
Thymoquinone
References
Abdel-Daim MM, Abdou RH (2015) Protective effects of diallyl sulfide and curcumin separately against thallium-induced toxicity in rats. Cell J 17:379–388
Abdel-Daim MM, Shaheen HM, Abushouk AI, Toraih EA, Fawzy MS, Alansari WS, Aleya L, Bungau S (2018) Thymoquinone and diallyl sulfide protect against fipronil-induced oxidative injury in rats. Environ Sci Pollut Res 25:23909–23916
Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126
Ahlatci A, Kuzhan A, Taysi S, Demirtas OC, Alkis HE, Tarakcioglu M, Demirci A, Caglayan D, Saricicek E, Cinar K (2014) Radiation-modifying abilities of Nigella sativa and thymoquinone on radiation-induced nitrosative stress in the brain tissue. Phytomedicine 21:740–744
Al-Shdefat RI, Abd-ElAziz MA, Al-Saikhan FI (2014) Genoprotective and genotoxic effects of thymoquinone on doxorubicin-induced damage in isolated human leukocytes. Trop J Pharm Res 13:2015–2020
Alavinia SJ, Mirvaghefi A, Farahmand H, Rafiee G, Alavinia SJ, Shiry N, Moodi S (2019) DNA damage, acetylcholinesterase activity, and hematological responses in rainbow trout exposed to the organophosphate malathion. Ecotoxicol Environ Saf 182:109311
Allain CC, Poon LS, Chan CS, Richmond W, Fu PC (1974) Enzymatic determination of total serum cholesterol. Clin Chem 20:470–475
Amin B, Hosseinzadeh H (2016) Black cumin (Nigella sativa) and its active constituent, thymoquinone: an overview on the analgesic and anti-inflammatory effects. Planta Med 82:8–16
Ansar S, Iqbal M (2016) Amelioration of ferric nitrilotriacetate-induced hepatotoxicity in Wistar rats by diallylsulfide. Hum Exp Toxicol 35:259–266
Armutcu F, Akyol S, Akyol O (2018) The interaction of glutathione and thymoquinone and their antioxidant properties. Electr J Gen Med 15:em59
Atteya M, Ahmed AM, AlRabiah A, Al-Matrafi TA, Arafah MM, Al-Saggaf S, Shereef SH, Ahmed AH, Alqahtani HM, Mohammad RAT (2019) Thymoquinone and curcumin modify iNOS, caspase-3, and thioredoxin immunohistochemical expression in acetaminophen (APAP) hepatotoxicity. Folia Morphol (Warsz) 78:773–788
Babson AL, Babson SR (1973) Kinetic colorimetric measurement of serum lactate dehydrogenase activity. Clin Chem 19:766–769
Ballantyne B, Marrs TC (1992) Clinical and experimental toxicology of organophosphates and carbamates. Elsevier
Basarslan F, Yilmaz N, Ates S, Ozgur T, Tutanc M, Motor VK, Arica V, Yilmaz C, Inci M, Buyukbas S (2012) Protective effects of thymoquinone on vancomycin-induced nephrotoxicity in rats. Hum Exp Toxicol 31:726–733
Beutler E, Duron O, Kelly BM (1963) Improved method for the determination of blood glutathione. J Lab Clin Med 61:882–888
Blasiak J, Stańkowska D (2001) Genotoxicity of malaoxon: induction of oxidized and methylated bases and protective effect of α-tocopherol. Pestic Biochem Physiol 71:88–96
Bucolo G, David H (1973) Quantitative determination of serum triglycerides by the use of enzymes. Clin Chem 19:476–482
Buratti FM, D'aniello A, Volpe MT, Meneguz A, Testai E (2005) Malathion bioactivation in the human liver: the contribution of different cytochrome p450 isoforms. Drug Metab Dispos 33:295–302
Coban FK, Ince S, Kucukkurt I, Demirel HH, Hazman O (2015) Boron attenuates malathion-induced oxidative stress and acetylcholinesterase inhibition in rats. Drug Chem Toxicol 38:391–399
Coulombe JJ, Favreau L (1963) A new simple semimicro method for colorimetric determination of urea. Clin Chem 9:102–108
Darakhshan S, Pour AB, Colagar AH, Sisakhtnezhad S (2015) Thymoquinone and its therapeutic potentials. Pharmacol Res 95:138–158
El-Sheikh AA, Morsy MA, Hamouda AH (2016) Protective mechanisms of thymoquinone on methotrexate-induced intestinal toxicity in rats. Pharmacogn Mag 12:S76
Ellman GL, Courtney KD, Andres V Jr, Feather-Stone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95
Farooqui Z, Shahid F, Khan AA, Khan F (2017) Oral administration of Nigella sativa oil and thymoquinone attenuates long term cisplatin treatment induced toxicity and oxidative damage in rat kidney. Biomed Pharmacother 96:912–923
Findikli HA, Bilge Z, Aydin H, Yuceer MM, Algin A, Aydin B (2018) The combination of acute pancreatitis and toxic hepatitis developing secondary to exposure to malathion : a case report. Acta Gastro-Enterol Belg 81:333–335
Flehi-Slim I, Chargui I, Boughattas S, El Mabrouk A, Belaid-Nouira Y, Neffati F, Najjar MF, Haouas Z, Ben Cheikh H (2015) Malathion-induced hepatotoxicity in male Wistar rats: biochemical and histopathological studies. Environ Sci Pollut Res Int 22:17828–17838
Gong P, Hu B, Cederbaum AI (2004) Diallyl sulfide induces heme oxygenase-1 through MAPK pathway. Arch Biochem Biophys 432:252–260
Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem 126:131–138
Ho C-Y, Lu C-C, Jhang J-J, Yen G-C (2017) Diallyl sulfide attenuates transforming growth factor-β-stimulated pulmonary fibrosis through Nrf2 activation in lung MRC-5 fibroblast. J Funct Foods 28:314–320
Ibrahim SS, Nassar NN (2008) Diallyl sulfide protects against N-nitrosodiethylamine-induced liver tumorigenesis: role of aldose reductase. World J Gastroenterol 14:6145–6153
Ince S, Kucukkurt I, Demirel HH, Turkmen R, Sever E (2012) Thymoquinone attenuates cypermethrin induced oxidative stress in Swiss albino mice. Pestic Biochem Physiol 104:229–235
Ince S, Kucukkurt I, Demirel HH, Turkmen R, Zemheri F, Akbel E (2013) The role of thymoquinone as antioxidant protection on oxidative stress induced by imidacloprid in male and female Swiss albino mice. Toxicol Environ Chem 95:318–329
Ince S, Arslan-Acaroz D, Demirel HH, Varol N, Ozyurek HA, Zemheri F, Kucukkurt I (2017) Taurine alleviates malathion induced lipid peroxidation, oxidative stress, and proinflammatory cytokine gene expressions in rats. Biomed Pharmacother 96:263–268
Ismail M, Al-Naqeep G, Chan KW (2010) Nigella sativa thymoquinone-rich fraction greatly improves plasma antioxidant capacity and expression of antioxidant genes in hypercholesterolemic rats. Free Radic Biol Med 48:664–672
Jadhav RK, Sharma VK, Rao GJ, Saraf AK, Chandra H (1992) Distribution of malathion in body tissues and fluids. Forensic Sci Int 52:223–229
Jagadeesan A, Vinayagam MM, Dharmalingam P (2014) Diallyl sulfide attenuates renal injury by altering the expressions of COX-2 and NF-κB during cisplatin-induced nephrotoxicity in male wistar rats. Biomed Prev Nutr 4:291–297
Kalayarasan S, Prabhu PN, Sriram N, Manikandan R, Arumugam M, Sudhandiran G (2009) Diallyl sulfide enhances antioxidants and inhibits inflammation through the activation of Nrf2 against gentamicin-induced nephrotoxicity in Wistar rats. Eur J Pharmacol 606:162–171
Larsen K (1972) Creatinine assay in the presence of protein with LKB 8600 Reaction Rate Analyser. Clin Chim Acta 38:475–476
Laskar AA, Khan MA, Rahmani AH, Fatima S, Younus H (2016) Thymoquinone, an active constituent of Nigella sativa seeds, binds with bilirubin and protects mice from hyperbilirubinemia and cyclophosphamide-induced hepatotoxicity. Biochimie 127:205–213
Lasram MM, Lamine AJ, Dhouib IB, Bouzid K, Annabi A, Belhadjhmida N, Ahmed MB, El Fazaa S, Abdelmoula J, Gharbi N (2014) Antioxidant and anti-inflammatory effects of N-acetylcysteine against malathion-induced liver damages and immunotoxicity in rats. Life Sci 107:50–58
Lin X, Yu S, Chen Y, Wu J, Zhao J, Zhao Y (2012) Neuroprotective effects of diallyl sulfide against transient focal cerebral ischemia via anti-apoptosis in rats. Neurol Res 34:32–37
Mansour M, Tornhamre S (2004) Inhibition of 5-lipoxygenase and leukotriene C4 synthase in human blood cells by thymoquinone. J Enzyme Inhib Med Chem 19:431–436
Mihara M, Uchiyama M (1978) Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem 86:271–278
Mnif W, Hassine AIH, Bouaziz A, Bartegi A, Thomas O, Roig B (2011) Effect of endocrine disruptor pesticides: a review. Int J Environ Res Public Health 8:2265–2303
Mohamed A, Shoker A, Bendjelloul F, Mare A, Alzrigh M, Benghuzzi H, Desin T (2003) Improvement of experimental allergic encephalomyelitis (EAE) by thymoquinone; an oxidative stress inhibitor. Biomed Sci Instrum 39:440–445
Nishikimi M, Appaji N, Yagi K (1972) The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen. Biochem Biophys Res Commun 46:849–854
Ojha A, Srivastava N (2014) In vitro studies on organophosphate pesticides induced oxidative DNA damage in rat lymphocytes. Mutat Res Genet Toxicol Environ Mutagen 761:10–17
Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70:158–169
Radad K, Hassanein K, Al-Shraim M, Moldzio R, Rausch WD (2014) Thymoquinone ameliorates lead-induced brain damage in Sprague Dawley rats. Exp Toxicol Pathol 66:13–17
Rao PSS, Midde NM, Miller DD, Chauhan S, Kumar A, Kumar S (2015) Diallyl sulfide: potential use in novel therapeutic interventions in alcohol, drugs, and disease mediated cellular toxicity by targeting cytochrome P450 2E1. Curr Drug Metab 16:486–503
Reitman S, Frankel S (1957) A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol 28:56–63
Richmond W (1973) Preparation and properties of a cholesterol oxidase from Nocardia sp. and its application to the enzymatic assay of total cholesterol in serum. Clin Chem 19:1350–1356
Sapbamrer R, Hongsibsong S (2014) Organophosphorus pesticide residues in vegetables from farms, markets, and a supermarket around Kwan Phayao Lake of Northern Thailand. Arch Environ Contam Toxicol 67:60–67
Savory J, Heintges MG, Sonowane M, Cross RE (1976) Measurement of total protein and albumin in serum with a centrifugal analyzer. Clin Chem 22:1102–1104
Sheen LY, Wu CC, Lii CK, Tsai SJ (2001) Effect of diallyl sulfide and diallyl disulfide, the active principles of garlic, on the aflatoxin B(1)-induced DNA damage in primary rat hepatocytes. Toxicol Lett 122:45–52
Suleria HAR, Butt MS, Khalid N, Sultan S, Raza A, Aleem M, Abbas M (2015) Garlic (Allium sativum): diet based therapy of 21st century–a review. Asian Pac J Trop Dis 5:271–278
Suratman S, Edwards JW, Babina K (2015) Organophosphate pesticides exposure among farmworkers: pathways and risk of adverse health effects. Rev Environ Health 30:65–79
Szasz G (1969) A kinetic photometric method for serum gamma-glutamyl transpeptidase. Clin Chem 15:124–136
Taubert D, Glockner R, Muller D, Schomig E (2006) The garlic ingredient diallyl sulfide inhibits cytochrome P450 2E1 dependent bioactivation of acrylamide to glycidamide. Toxicol Lett 164:1–5
Tchounwou PB, Patlolla AK, Yedjou CG, Moore PD (2015) Environmental exposure and health effects associated with malathion toxicity. Tox Haz Agrochem 51:2145–2149
Tietz NW, Burtis CA, Duncan P, Ervin K, Petitclerc CJ, Rinker AD, Shuey D, Zygowicz ER (1983) A reference method for measurement of alkaline phosphatase activity in human serum. Clin Chem 29:751–761
Whitehead TP, Bevan EA, Miano L, Leonardi A (1991) Defects in diagnostic kits for determination of urate in serum. Clin Chem 37:879–881
Yokota K, Fukuda M, Katafuchi R, Okamoto T (2017) Nephrotic syndrome and acute kidney injury induced by malathion toxicity. BMJ Case Rep. https://doi.org/10.1136/bcr-2017-220733
Zidan AA, El-Ashmawy NE, Khedr EG, Ebeid EM, Salem ML, Mosalam EM (2018) Loading of doxorubicin and thymoquinone with F2 gel nanofibers improves the antitumor activity and ameliorates doxorubicin-associated nephrotoxicity. Life Sci 207:461–470
Acknowledgements
This research was funded by the Deanship of Scientific Research at Princess Nourah bint Abdulrahman University through the Fast-track Research Funding Program. The authors extend their appreciation to the Deanship of Scientific Research at King Khalid University, Abha, KSA, for funding this work under grant number (G.R.P.-248-39).
Funding
This research was funded by the Deanship of Scientific Research at Princess Nourah bint Abdulrahman University through the Fast-track Research Funding Program. The authors extend their appreciation to the Deanship of Scientific Research at King Khalid University, Abha, KSA, for funding this work under grant number (G.R.P.-248-39).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare that they have no competing interests.
Additional information
Responsible Editor: Philippe Garrigues
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Abdel-Daim, M.M., Abushouk, A.I., Bungău, S.G. et al. Protective effects of thymoquinone and diallyl sulphide against malathion-induced toxicity in rats. Environ Sci Pollut Res 27, 10228–10235 (2020). https://doi.org/10.1007/s11356-019-07580-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11356-019-07580-y