Platelet dopamine receptors and oxidative stress parameters as markers of manganese toxicity

Abstract

The present study has been undertaken to investigate whether neurotoxic effects of manganese (Mn) are reflected in platelets in rats to monitor the usefulness of platelet as peripheral model. Exposure of rats to Mn (10 or 15 mg/kg bw, i.p.) for 45 days caused a significant increase in membrane fluidity as evidenced by decrease in fluorescence polarisation in platelets (11% and 14%) and striatum (9% and 13%). These rats exhibited a significant increase in superoxide dismutase activity both in platelets (24% and 37%) and striatum (31% and 42%), respectively, in comparison to controls. Exposure of rats to Mn for 45 days (15 mg/kg bw, i.p.) caused a significant decrease in reduced glutathione content (platelets 20%, striatum 24%) and catalase activity (platelets 35%, striatum 44%) compared to control rats. Rats exposed to Mn (10 or 15 mg/ kg bw, i.p.) for 15 days exhibited a significant increase in dopamine receptors both in platelets (55% and 40%) and striatum (38% and 31%). The results suggest that exposure to Mn may alter the membrane functions and impair the anti-oxidant defense mechanism both in platelets and brain. The study also suggests that dopaminergic mechanisms are impaired following Mn exposure and such changes are reflected in platelets. Interestingly, parallel changes both in striatum and platelets, as observed in the present study, strengthen the usefulness of platelets as a peripheral neuronal model.

Keywords

manganese brain platelets dopamine receptors oxidative stress

References

Pal PK , Samii A , Calne DB . Manganese neurotoxicity: a review of clinical features, imaging and pathology . Neurotoxicology 1999; 20: 227–238 .

Wenberg A , Iregren A , Struwe G , Cizinsky G , Hagman MM , Johnsson L . Manganese exposure in steel smelters a health hazard to the nervous system . Scand J Work Environ Health 1999; 17: 255–272 .

Zayed J , Vyskocil A , Kennedy G . Environmental contamination and human exposure to manganese contribution of methylcyclopentadienyl manganese tricarbonylin unleaded gasoline . Int Arch Occup Environ Health 1999; 72: 7–13 .

Prohaska JR . Functions of trace elements in brain metabolism . Physiol Rev 1987; 67: 858–901 .

Wedler FC . Biological significance of manganese in mammalian systems. In Ellis GP , Luscombe DK (Eds). Progress in medicinal chemistry, Volume 30. Amsterdam: Elsevier ,1993, pp. 89–133.

Calne DB , Chu NS , Huang CC , Lu CS , Olanow W . Manganism and idiopathic parkinsonism: similarity and differences . Neurology 1994; 44: 1583–1586 .

Chia SE , Foo SC , Gan SL , Jeyaratnam J , Tian CS . Neurobehavioural functions among workers exposed to manganese ore . Scand J Work 1993; 19: 264–270 .

Hudnell HK . Effect from environmental Mn exposure: a review of the evidence from non occupational exposure studies . Neurotoxicology 1999; 20: 379–398 .

Smargiassi A , Mutti A . Peripheral markers and exposure to manganese . Neurotoxicology 1999; 20: 401–406 .

10.

Seth PK , Hong JS , Kilts CD , Bondy SC . Alteration in cerebral neurotransmitter receptor function by exposure of rats to manganese . Toxicol Lett 1981; 9: 247–254 .

11.

Aschner M . Manganese neurotoxicity and oxidative stress. In Connor JR (Ed). Metals and oxidative damage in neurological disorders. New York: Plenum , 1997, pp. 77–93.

12.

Rehavi M , Weizman R , Wiezman A . Platelet as a neuronal model in neuropsychiatric disorders. In Jamieson GA (Ed). Platelet membrane receptors: molecular biology, immunology, biochemistry and pathology, Volume 100. New York: AR Liss , 1988, pp. 569–583.

13.

Da Prada M , Cesura AM , Launay JM , Richards JG . Platelets as a model for neurons? Experientia 1988; 44: 115–126 .

14.

Seth PK , Khanna VK , Sah R . Can blood platelet neurotransmitters serve as a neuronal model? In Dhawan BN , Raghubir R , Rapaka RS (Eds). Recent advances in the study of neurotransmitter receptors. Drug research perspectives: a CDRI series, Volume 17. Lucknow: Hindustani Book Depot , 1994, pp. 138–156.

15.

Khanna AS , Agarwal AK , Seth PK . Interactions of selected neurotoxicants on specific [3H]-5-hydroxytryptamine and [3H]-spiperone binding sites in rat blood platelets . Biochem Arch 1987; 3: 307–316 .

16.

Srivastava S , Joshi CS , Sethi PPS , Agrawal AK , Srivastava SK , Seth PK . Altered platelet functions in non-insulin dependent diabetes mellitus (NIDDM) . Thromb Res 1994; 76: 451–461 .

17.

Saxena S , Kumar D , Srivastava P , Khanna VK , Seth PK . Low levels of platelet glutathione in Eales' disease . Med Sci Res 1999; 27: 625–628 .

18.

Srivastava P , Saxena S , Khanna VK , Kumar D , Nath R , Seth PK . Raised platelet thiobarbituric acid reacting substances in proliferative Eales' disease . Indian J Ophthalmol 2000; 48: 307–309 .

19.

Buchet JP , Magos C , Roels H , Ceulemans E , Lauwerys R . Urinary excretion of homovanillic acid in workers exposed to manganese . Int Arch Occup Environ Health 1993; 65: 131–133 .

20.

Mutti A , Bergamashi E , Alinovi R , Lucchini R , Vettori MV , Franchini I . Serum prolactin in subjects occupationally exposed to manganese . Ann Clin Lab Sci 1996; 26: 10–17 .

21.

Glowinski J , Iversion LL . Regional studies of catecholamines in rat brain; the disposition of [3H]-dopamine and [3H]-DOPA in various regions of the brain . J Neurochem 1966; 13: 655–659 .

22.

Khanna VK , Husain R , Seth PK . Effect of protein malnutrition on the neurobehavioural toxicity of styrene on young rats . J Appl Toxicol 1994; 14: 351–356 .

23.

Khanna AS , Agrawal AK , Seth PK . [3H]- Spiperone binding sites in blood platelets . Biochem Biophys Res Commun 1987; 146: 983–988 .

24.

Shinitzky M , Barenholz Y . Fluidity parameters of lipid regions determined by fluorescence polarisation . Biochim Biophys Acta 1978; 515: 367–394 .

25.

Hasan M , Haider SS . Acetyl-homocystein thiolactone protects against some neurotoxic effects of thallium . Neurotoxicology 1989; 10: 257–262 .

26.

Kakkar P , Das B , Viswanathan PN . A modified spectrophotometric assay of superoxide dismutase . Indian J Biochem Biophys 1984; 21: 130–132 .

27.

Sinha AK . Colorimetric assay of catalase . Anal Biochem 1972; 47: 389–394 .

28.

Lowry OH , Rosenberg MJ , Farr AL , Randall RJ . Protein measurement with the Folin phenol reagents . J Biol Chem 1951; 192: 265–275 .

29.

Liccione JJ , Maines DM . Selective vulnerability of glutathione metabolism and cellular defence mechanism in rat striatum to manganese . J Pharmacol Exp Ther 1988; 24: 156–161 .

30.

Desole MS , Esposito G , Migheli R , Fresu L , Sircana S , Miele M , De Natale G , Miele E . Allopurinol protects against manganese induced oxidative stress in striatum and in brain stem of rat . Neurosci Lett 1995; 182: 73–76 .

31.

Keen CL , Lonnerdal B , Hurley LS . Manganese. In Frieden E (Ed). Biochemistry of the essential ultratrace element. New York: Plenum , 1984, pp. 89–132.

32.

Hussain S , Lipe GW , Slikker Jr W , Ali SF . The effect of chronic exposure of manganese on antioxidant enzymes in different regions of rat brain . Neurosci Res Commun 1997; 21: 135–144 .

33.

Davis CD , Greger JL . Longitudinal changes of manganese dependent superoxide dismutase and other indexes of manganese and iron status in women . Am J Clin Nutr 1992; 55: 747–752 .

34.

Thompson KH , Godin DV , Lee M . Tissue antioxidant status in streptozotocin-induced diabetes in rats. Effect of dietary manganese deficiency . Biol Trace Elem Res 1992; 35: 213–224 .

35.

Thongphasuk J , Oberley LW , Oberleyl TD . Induction of superoxide dismutase and cytotoxicity and manganese in human breast cancer cells . Arch Biochem Biophys 1999; 365: 317–327 .

36.

Jones OP , Thor H , Anderson B , Orrenius S . Detoxification reactions in isolated hepatocytes, role of glutathione peroxidase, catalase and formaldehyde dehydrogenase in reactions relating to N-demethylation by the cytochrome P-450 . J Biol Chem 1987; 253: 6031–6037 .

37.

Kumar R , Srivastava S , Agrawal AK , Seth PK . Alteration in some membrane properties in rat brain following exposure to manganese . Pharmacol Toxicol 1996; 79: 47–48 .

38.

Chiueh CC , Murphy DL , Miyake H , Lang K , Tulsi PK , Huang SJ . Hydroxyl free radical (OH) formation reflected by salicylate hydroxylation and neuromelanin. In vivo markers for oxidant injury of nigral neurons . Ann NY Acad Sci 1993; 679: 370–382 .

39.

Zaidi NF , Agarwal AK , Srivastava SP , Seth PK . Effect of gestational and neonatal styrene exposure on dopamine receptors . Neurobehav Toxicol Teratol 1985; 7: 99–103 .

40.

Khanna VK , Husain R , Hanig JP , Seth PK . Increased neurobehavioral toxicity of styrene in protein malnourished rats . Neurotoxicol Teratol 1991; 13: 153–159 .

41.

Agrawal AK , Seth PK , Squibb RE , Tilson HA , Uphouse LL , Bondy SC . Neurotransmitter receptors in brain in acrylamide treated rats: I. Effect of single exposure to acrylamide . Physiol Biochem Behav 1981; 14: 527–534 .