Invulnerability of bromelain against oxidative degeneration and cholinergic deficits imposed by dichlorvos in mice brains

Abstract

BACKGROUND: The present study elucidates the protective potential of bromelain against dichlorvos intoxication in mice brains. Dichlorvos induces the oxidative stress by disproportionating the balance between free radicals generation and their scavenging in neurons which leads to neuronal degeneration.

METHODS: In this study, mice were divided into four groups- group I (control), group II (dichlorvos treated), group III (bromelain treated) and group IV (exposed to both bromelain and dichlorvos both).

RESULTS: Dichlorvos treatment increased the levels of thiobarbituric acid reactive substances (TBARS) and protein carbonyl content (PCC) which indicate the increased oxidative stress. Meanwhile, brain endogenous antioxidants and cholinesterases level was decreased after dichlorvos exposure. Levels of TBARS and PCC decreased whereas cholinesterases level was recorded to be elevated after bromelain exposure.

CONCLUSION: Bromelain offered neuroprotection by decreasing oxidative stress and augmenting cholinesterases in mice brains. This study highlights the invulnerability of bromelain against oxidative and cholinergic deficits in mice brains.

Key words： oxidative stress; dichlorvos; bromelain; neuroprotection; neurotransmitter

Acknowledgments

We thank Banasthali University and Department of Science and Technology (DST), India for providing the facilities for present investigation.

Compliance with ethics guidelines

Bharti Chaudhary, Sonam Agarwal and Renu Bist declare that they have no conflict of interest.

References

1 Abdelsalam E B (1999). Neurotoxic potential of six organophosphorus compounds in adult hens. Vet Hum Toxicol. 141(5): 290–292

2 Agency for Toxic Substances and Disease Registry (ATSDR) Richte P, Corcoran J (1997). Toxicological Profile for Dichlorvos. Agency for Toxic Substances and Disease Registry, Atlanta, USA

3 Assis C R, Amaral I P, Castro P F, Carvalho L B, Bezerra R S (2007). Effect of dichlorvos on the acetylcholinesterase from tambaqui (Colossoma macropomum) brain. Environ Toxicol Chem, 26(7): 1451–1453

PMID

4 Assis C R, Linhares A G, Oliveira V M, França R C, Carvalho E V, Bezerra R S, de Carvalho L B Jr (2012). Comparative effect of pesticides on brain acetylcholinesterase in tropical fish. Sci Total Environ, 441: 141–150

PMID

5 Atanasov V N, Petrova I, Dishovsky C (2013). In vitro investigation of efficacy of new reactivators on OPC inhibited rat brain acetylcholinesterase. Chem Biol Interact, 203(1): 139–143

PMID

6 Bhattacharyya B K (2008). Bromelain: an overview. Nat Prod Rad, 7(4): 359–363

7 Binukumar B K, Bal A, Kandimalla R J L, Gill K D (2010). Nigrostriatal neuronal death following chronic dichlorvos exposure: crosstalk between mitochondrial impairments, α synuclein aggregation, oxidative damage and behavioral changes. Mol Brain, 3(35): 35

PMID

8 Cankayali I, Demirag K, Eris O, Ersoz B, Moral A R (2005). The effects of N-acetylcysteine on oxidative stress in organophosphate poisoning model. Adv Ther, 22(2): 107–116

PMID

9 Carod-Artal F J, Speck-Martins C (1999). [Late onset polyneuropathy due to exposure to organophosphates]. Rev Neurol, 29(2): 123–127

PMID

10 Celik I, Yilmaz Z, Turkoglu V (2009). Hematotoxic and hepatotoxic effects of dichlorvos at sublethal dosages in rats. Environ Toxicol, 24(2): 128–132

PMID

11 Chandler D S, Mynott T L (1998). Bromelain protects piglets from diarrhoea caused by oral challenge with K88 positive enterotoxigenic Escherichia coli. Gut, 43(2): 196–202

PMID

12 Chaudhary B, Agrawal S, Bist R (2014). Obliteration in Oxidative Stress and Ca++ Uptake in Brain Mitochondria Leads to Impairment of Cholinergic System: A Possible Mechanism Underlying Neurotoxicity Induced by Dichlorvos. BBB, 2: 550–564

13 Choudhary S, Raheja G, Gupta V, Gill K D (2002). Possible involvement of dopaminergic neurotransmitter system in dichlorvos induced delayed neurotoxicity. J Biochem Mol Biol Biophys, 6(1): 29–36

PMID

14 Claiborne A (1985). Catalase Activity: In Greenwald RA (Ed.) CRC Handbook of Methods in Oxygen Radical Research. CRC Press, Boca Raton, FL. 283–284

15 Dhindsa R S, Plumb-Dhindsa P, Thorpe T A (1981). Leaf senescence: correlated with increased level of membrane permeability and lipid peroxidation and decreased levels of Superoxide dismutase and Catalase. J Exp Bot, 32(1): 93–101

16 Eckert K, Grabowska E, Stange R, Schneider U, Eschmann K, Maurer H R (1999). Effects of oral bromelain administration on the impaired immunocytotoxicity of mononuclear cells from mammary tumor patients. Oncol Rep, 6(6): 1191–1199

PMID

17 Ellman G L (1959). Tissue sulfhydryl groups. Arch Biochem Biophys, 82(1): 70–77

PMID

18 Ellman G L, Courtney K D, Andres V Jr, Feather-Stone R M (1961). A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol, 7(2): 88–95

PMID

19 Eroğlu H E (2009). Toxic nuclear effects of the organophosphorus insecticide Dichlorvos (DDVP) in human peripheral blood lymphocytes. Acta Biol Hung, 60(4): 409–416

PMID

20 Gallo M A, Lawryk N J (1991). Organic phosphorus pesticides. In Handbook of Pesticide Toxicology. Hayes W J Jr, and Laws E R Jr., Eds. New York: Acad Press, 5: 917–1123

21 Gaspari R J, Paydarfar D (2011). Dichlorvos-induced central apnea: effects of selective brainstem exposure in the rat. Neurotoxicology, 32(2): 206–214

PMID

41 HabigW H, Pabst M J, Jakoby W B (1974). Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem, 249(22): 7130–7139

22 Habashi S A, Moghimi A, Sabouni F, Majd S A (2012). Inhibition of NO production in LPS-stimulated primary rat microglial cells by Bromelain. J of Cell and Mol Res, 3(2): 57–65

23 Hale L P (2004). Proteolytic activity and immunogenicity of oral bromelain within the gastrointestinal tract of mice. Int Immunopharmacol, 4(2): 255–264

PMID

24 Hale L P, Greer P K, Sempowski G D (2002). Bromelain treatment alters leukocyte expression of cell surface molecules involved in cellular adhesion and activation. Clin Immunol, 104(2): 183–190

PMID

25 Hale L P, Greer P K, Trinh C T, Gottfried M R (2005). Treatment with oral bromelain decreases colonic inflammation in the IL-10-deficient murine model of inflammatory bowel disease. Clin Immunol, 116(2): 135–142

PMID

26 Hinz V, Grewig S, Schmidt B H (1996). Metrifonate and dichlorvos: effects of a single oral administration on cholinesterase activity in rat brain and blood. Neurochem Res, 21(3): 339–345

PMID

27 Jones D P (2006). Redefining oxidative stress. Antioxid Redox Signal, 8(9-10): 1865–1879

PMID

28 Kangralkar V A, Shivraj D, Patil , Bandivadekar R M (2010). Oxidative stress and diabetes: A review. International J of Pharmaceut App, 1(1): 38–45

42 Kaur P, Radotra B, Minz R W, Gill K D (2007). Impaired mitochondrial energy metabolism and neuronal apoptotic cell death after chronic dichlorvos (OP) exposure in rat brain. Neurotoxicol, 28(6): 1208–1219

29 Lauer D, Reichenbach A, Birkenmeier G (2001). Alpha 2-macroglobulin-mediated degradation of amyloid beta 1--42: a mechanism to enhance amyloid beta catabolism. Exp Neurol, 167(2): 385–392

PMID

30 Lotz-Winter H (1990). On the pharmacology of bromelain: an update with special regard to animal studies on dose-dependent effects. Planta Med, 56(3): 249–253

PMID

31 Maurer H R (2001). Bromelain: biochemistry, pharmacology and medical use. Cell Mol Life Sci, 58(9): 1234–1245

PMID

32 Mohandas J, Marshal J, Duggin G, Horvath J S, Tiller D (1984). Differential distribution of glutathione and glutathione related enzymes in rabbit kidney. Cancer Res, 44: 5086–5091

PMID

33 Ohkawa H, Ohishi N, Yagi K (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem, 95(2): 351–358

PMID

34 Peña-Llopis S, Ferrando M D, Peña J B (2003). Increased recovery of brain acetylcholinesterase activity in dichlorvos-intoxicated European eels Anguilla anguilla by bath treatment with N-acetylcysteine. Dis Aquat Organ, 55(3): 237–245

PMID

35 Raheja G, Gill K D (2002). Calcium homeostasis and dichlorvos induced neurotoxicity in rat brain. Mol Cell Biochem, 232(1-2): 13–18

PMID

43 Reznick A Z,Packer L (1994). Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Methods Enzymol, 233: 357–363

44 Roger A (2006). Bromelain. Plast Reconstr Surg, 118(7): 1640–1644

36 Sarin S, Gill K D (1999). Dichlorvos induced alterations in glucose homeostasis: possible implications on the state of neuronal function in rats. Mol Cell Biochem, 199(1-2): 87–92

PMID

45 Savolainen K (2001). Understanding the toxic action of organophosphates. In: Krieger R I, editor. Handbook of Pesticide Toxicology, 2:1013–1043

37 Schulz H, Nagymajtényi L, Dési I (1995). Life-time exposure to dichlorvos affects behaviour of mature rats. Hum Exp Toxicol, 14(9): 721–726

PMID

46 Sharma P, Singh R (2012). Dichlorvos and lindane induced oxidative stress in rat brain: Protective effects of ginger. Pharmacognosy Res, 4(1): 27–32

47 Shenouda J, Green P, Sultatos L (2009). An evaluation of the inhibition of human butyrylcholinesterase and acetylcholinesterase by the organophosphate chlorpyrifosoxon. Toxicol Appl Pharmacol, 241(2): 135–142

38 Silva K C, Assis C R, Oliveira V M, Carvalho L B Jr, Bezerra R S (2013). Kinetic and physicochemical properties of brain acetylcholinesterase from the peacock bass (Cichla ocellaris) and in vitro effect of pesticides and metal ions. Aquat Toxicol, 126: 191–197

PMID

39 U.S. Environmental Protection Agency (2006). Interim Reregistration Eligibility Decision for Dichlorvos (DDVP). Vet Hum Toxicol, 41(5): 290–292

48 Xing H, Wang X, Sun G, Gao X, Xu S, Wang X (2012). Effects of atrazine and chlorpyrifos on activity and transcription of glutathione S-transferase in common carp (Cyprinuscarpio L.). Environ Toxicol Pharmacol, 33(2): 233–244

40 Yadav P, Jadhav S E, Kumar V, Kaul K K, Pant S C, Flora S J S (2012). Protective efficacy of 2-PAMCl, atropine and curcumin against dichlorvos induced toxicity in rats. Interdiscip Toxicol, 5(1): 1–8

PMID

49 Yoshikawa T, Naito Y (2002). What Is Oxidative Stress? J of the Japan Med Association, 45(7): 271–276