Chronic consumption of cassava juice induces cellular stress in rat substantia nigra

Document Type: Original Article

Authors

1 Posgrado en Neuroetología, Instituto de Neuroetología, Universidad Veracruzana. Xalapa, Veracruz. Mexico

2 Facultad de Química Farmacéutica Biológica, Universidad Veracruzana. Xalapa, Veracruz. Mexico

3 Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla. Puebla, Puebla. Mexico

4 IIIT Srikakulam, Rajiv Gandhi University of Knowledge Technologies (RGUKT); International collaboration ID: 1840; India

5 Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suárez”. Ciudad de México. Mexico

6 Laboratorio de Neurofarmacología, Instituto de Neuroetología, Universidad Veracruzana, Xalapa, Veracruz. Mexico

7 CONACyT-Instituto de Neuroetología, Universidad Veracruzana. Xalapa, Veracruz. Mexico

Abstract

Objective(s): Cassava (Manihot esculenta Crantz) contains cyanogenic glycosides (linamarin and lotaustralin) that have been associated with neurological disorders in humans and rats. In basal ganglia, the dopaminergic neurons of substantia nigra pars compacta (SNpc) show high cytotoxic susceptibility; therefore, the chronic consumption of cassava (CCC) could induce neurodegeneration in SNpc.  In this study we examine the impact of CCC on the integrity of the nigrostriatal system, including apoptosis and microgliosis.
Materials and Methods: Male Wistar rats were administered cassava juice daily (3.57 g/kg and 28.56 g/kg, per os) or linamarin (0.15  mg/ml, IP), and its effects were evaluated in rota-rod and swim tests at days 7, 14, 21, 28, and 35 of administration. In SNpc, oxidative/nitrosative stress was determined by malondialdehyde/4-hydroxyalkenals (MDA-4-HAD) and nitrite contents. Tyrosine hydroxylase immunoreactivity (TH-IR) was evaluated in SNpc, neostriatum (NE), and nucleus accumbens (NA). Apoptosis and microgliosis were determined by active-caspase-3 (C3) and CD11b/c (OX42) expression in the medial region of SNpc.
Results: Chronic administration of cassava juice, or linamarin, increased motor impairment. The rats that received 28.56 g/kg cassava showed increased MDA-4-HAD content in SNpc and nitrite levels in NE with respect to controls. Significant loss of TH-IR in SNpc, NE, and NA was not found. The 28.56 g/kg cassava administration produced dopaminergic atrophy and microgliosis, whereas linamarin induced hypertrophy and C3-related apoptosis in SNpc.
Conclusion: CCC induces cellular stress on dopaminergic neurons, which could contribute to motor impairment in the rat.

Keywords


1. Rivadeneyra-Dominguez E, Vazquez-Luna A, Rodriguez-Landa JF, Diaz-Sobac R. Neurotoxic effect of linamarin in rats associated with cassava (Manihot esculenta Crantz) consumption. Food Chem Toxicol 2013; 59:230-235.
2. Li S, Cui Y, Zhou Y, Luo Z, Liu J, Zhao M. The industrial applications of cassava: current status, opportunities and prospects. J Sci Food Agric 2017; 97:2282-2290.
3. Morgan NK, Choct M. Cassava: Nutrient composition and nutritive value in poultry diets. Anim Nutr 2016; 2:253-261.
4. Talsma EF, Borgonjen-van den Berg KJ, Melse-Boonstra A, Mayer EV, Verhoef H, Demir AY, et al. The potential contribution of yellow cassava to dietary nutrient adequacy of primary-school children in Eastern Kenya; the use of linear programming. Public Health Nutr 2018; 21:365-376.
5. Mombo S, Dumat C, Shahid M, Schreck E. A socio-scientific analysis of the environmental and health benefits as well as potential risks of cassava production and consumption. Environ Sci Pollut Res Int 2017; 24:5207-5221.
6. De Moura FF, Moursi M, Lubowa A, Ha B, Boy E, Oguntona B, et al. Cassava intake and vitamin A status among women and preschool children in Akwa-Ibom, Nigeria. PLoS One 2015; 10:e0129436.
7. Padmaja G. Cyanide detoxification in cassava for food and feed uses. Crit Rev Food Sci Nutr 1995; 35:299-339.
8. Zidenga T, Siritunga D, Sayre RT. Cyanogen metabolism
in cassava roots: Impact on protein synthesis and root
development. Front Plant Sci 2017; 8:1-12.
9. Montagnac JA, Davis CR, Tanumihardjo SA. Nutritional value of cassava for use as a staple food and recent advances for improvement. Compr Rev Food Sci Food Saf 2009; 8:181-194.
10. Tshala-Katumbay DD, Ngombe NN, Okitundu D, David L, Westaway SK, Boivin MJ, et al. Cyanide and the human brain: perspectives from a model of food (cassava) poisoning. Ann N Y Acad Sci 2016; 1378:50-57.
11. Adamolekun B. Neurological disorders associated with cassava diet: a review of putative etiological mechanisms. Metab Brain Dis 2011; 26:79-85.
12. Njoh J. Tropical ataxic neuropathy in Liberians. Trop Geogr Med 1990; 42:92-94.
13. Cliff J, Muquingue H, Nhassico D, Nzwalo H, Bradbury JH. Konzo and continuing cyanide intoxication from cassava in Mozambique. Food Chem Toxicol 2011; 49:631-635.
14. Kambale KJ, Ali ER, Sadiki NH, Kayembe KP, Mvumbi LG, Yandju DL, et al. Lower sulfurtransferase detoxification rates of cyanide in konzo-A tropical spastic paralysis linked to cassava cyanogenic poisoning. Neurotoxicology 2017; 59:256-262.
15. Kashala-Abotnes E, Okitundu D, Mumba D, Boivin MJ, Tylleskar T, Tshala-Katumbay D. Konzo: a distinct neurological disease associated with food (cassava) cyanogenic poisoning. Brain Res Bull 2018; 2019; 145: 87-91.
16. Bumoko GM, Sombo MT, Okitundu LD, Mumba DN, Kazadi KT, Tamfum-Muyembe JJ, et al. Determinants of cognitive performance in children relying on cyanogenic cassava as staple food. Metab Brain Dis 2014; 29:359-366.
17. Llorens J, Soler-Martin C, Saldana-Ruiz S, Cutillas B, Ambrosio S, Boadas-Vaello P. A new unifying hypothesis for lathyrism, konzo and tropical ataxic neuropathy: nitriles are the causative agents. Food Chem Toxicol 2011; 49:563-570.
18. Tor-Agbidye J, Palmer VS, Lasarev MR, Craig AM, Blythe LL, Sabri MI, et al. Bioactivation of cyanide to cyanate in sulfur amino acid deficiency: relevance to neurological disease in humans subsisting on cassava. Toxicol Sci 1999; 50:228-235.
19. Rivadeneyra-Dominguez E, Rodriguez-Landa JF. Motor impairments induced by microinjection of linamarin in the dorsal hippocampus of Wistar rats. Neurologia 2016; 31:516-522.
20. Rivadeneyra-Dominguez E, Vazquez-Luna A, Diaz-Sobac R, Briones-Cespedes EE, Rodriguez-Landa JF. Contribution of hippocampal area CA1 to acetone cyanohydrin-induced loss of motor coordination in rats. Neurologia 2017; 32:230-235.
21. Rivadeneyra-Dominguez E, Vazquez-Luna A, Rodriguez-
Landa JF, Diaz-Sobac R. A standardized extract of Ginkgo biloba
prevents locomotion impairment induced by cassava juice in
Wistar rats. Front Pharmacol 2014; 5:1-6.
22. Soto-Blanco B, Gorniak SL. Toxic effects of prolonged administration of leaves of cassava (Manihot esculenta Crantz) to goats. Exp Toxicol Pathol 2010; 62:361-366.
23. Soler-Martin C, Riera J, Seoane A, Cutillas B, Ambrosio S, Boadas-Vaello P, et al. The targets of acetone cyanohydrin neurotoxicity in the rat are not the ones expected in an animal model of konzo. Neurotoxicol Teratol 2010; 32:289-294.
24. Udeme N, Okafor P, Eleazu C. The metabolic effects of consumption of yellow cassava (Manihot esculenta Crantz) on some biochemical parameters in experimental rats. Int J Toxicol 2015; 34:559-564.
25. Kassa RM, Kasensa NL, Monterroso VH, Kayton RJ, Klimek JE, David LL, et al. On the biomarkers and mechanisms of konzo, a distinct upper motor neuron disease associated with food (cassava) cyanogenic exposure. Food Chem Toxicol 2011; 49:571-578.
26. Cunha LA, Mota TC, Cardoso PC, Alcantara DD, Burbano RM, Guimaraes AC, et al. In vitro assessment of the genotoxic and cytotoxic effects of boiled juice (tucupi) from Manihot esculenta Crantz roots. Genet Mol Res 2016; 15-22.
27. Kirik D, Rosenblad C, Bjorklund A. Characterization of behavioral and neurodegenerative changes following partial lesions of the nigrostriatal dopamine system induced by intrastriatal 6-hydroxydopamine in the rat. Exp Neurol 1998; 152:259-277.
28 .Hernandez-Baltazar D, Zavala-Flores LM, Villanueva-Olivo A. The 6-hydroxydopamine model and parkinsonian pathophysiology: Novel findings in an older model. Neurologia 2017; 32:533-539.
29. Hirsch EC, Faucheux B, Damier P, Mouatt-Prigent A, Agid Y. Neuronal vulnerability in Parkinson’s disease. J Neural Transm Suppl 1997; 50:79-88.
30. Sotocinal SG, Sorge RE, Zaloum A, Tuttle AH, Martin LJ,
Wieskopf JS, et al. The Rat Grimace Scale: a partially automated
method for quantifying pain in the laboratory rat via facial
expressions. Mol Pain 2011; 7:1-10.
31. Tillmann S, Wegener G. Syringe-feeding as a novel delivery method for accurate individual dosing of probiotics in rats. Benef Microbes 2018; 9:311-315.
32. Dunham NW, Miya TS. A note on a simple apparatus for detecting neurological deficit in rats and mice. J Am Pharm Assoc Am Pharm Assoc 1957; 46:208-209.
33. Tomas-Sanchez C, Blanco-Alvarez VM, Gonzalez-Barrios JA, Martinez-Fong D, Garcia-Robles G, Soto-Rodriguez G, et al. Prophylactic chronic zinc administration increases neuroinflammation in a hypoxia-Ischemia model. J Immunol Res 2016; 2016:4039837.
34. Hernandez-Baltazar D, Mendoza-Garrido ME, Martinez-Fong D. Activation of GSK-3beta and caspase-3 occurs in Nigral dopamine neurons during the development of apoptosis activated by a striatal injection of 6-hydroxydopamine. PLoS One 2013; 8:e70951.
35. Nadella R, Voutilainen MH, Saarma M, Gonzalez-Barrios
JA, Leon-Chavez BA, Jimenez JM, et al. Transient transfection
of human CDNF gene reduces the 6-hydroxydopamineinduced
neuroinflammation in the rat substantia nigra. J
Neuroinflammation 2014; 11:1-18.
36. Gasbarri A, Pompili A, Pacitti C, Cicirata F. Comparative effects of lesions to the ponto-cerebellar and olivo-cerebellar pathways on motor and spatial learning in the rat. Neuroscience 2003; 116:1131-1140.
37. Silva NA, Sousa RA, Fraga JS, Fontes M, Leite-Almeida H, Cerqueira R, et al. Benefits of spine stabilization with biodegradable scaffolds in spinal cord injured rats. Tissue Eng Part C Methods 2013; 19:101-108.
38. Hernandez-Baltazar, R. N, Rovirosa-Hernandez MJ, Zavala-Flores LM, Rosas-Jarquin CJ. Animal model of Parkinson disease: Neuroinflammation and apoptosis in the 6-hydroxydopamine induced model.  Experimental Animal Models of Human Diseases- an Effective Therapeutic Strategy. London: Intechopen; 2018.
39. Song J, Kim J. Degeneration of dopaminergic neurons due
to metabolic alterations and Parkinson’s Disease. Front Aging
Neurosci 2016; 8:1-11.
40. Kumar H, Lim HW, More SV, Kim BW, Koppula S, Kim IS, et al. The role of free radicals in the aging brain and Parkinson’s Disease: convergence and parallelism. Int J Mol Sci 2012; 13:10478-10504.
41. Cheignon C, Tomas M, Bonnefont-Rousselot D, Faller P, Hureau C, Collin F. Oxidative stress and the amyloid beta peptide in Alzheimer’s disease. Redox Biol 2018; 14:450-464.
42. Filler K, Lyon D, Bennett J, McCain N, Elswick R, Lukkahatai N, et al. Association of mitochondrial dysfunction and fatigue: A review of the literature. BBA Clin 2014; 1:12-23.
43. Leavesley HB, Li L, Prabhakaran K, Borowitz JL, Isom GE. Interaction of cyanide and nitric oxide with cytochrome c oxidase: implications for acute cyanide toxicity. Toxicol Sci 2008; 101:101-111.
44. Cobb CA, Cole MP. Oxidative and nitrative stress in neurodegeneration. Neurobiol Dis 2015; 84:4-21.
45. Dorado-Martinez C, Paredes-Carbajal C, Mascher D, Borgonio-Perez G, Rivas-Arancibia S. Effects of different ozone doses on memory, motor activity and lipid peroxidation levels, in rats. Int J Neurosci 2001; 108:149-161.
46. Riudavets MA, Iacono D, Resnick SM, O’Brien R, Zonderman AB, Martin LJ, et al. Resistance to Alzheimer’s pathology is associated with nuclear hypertrophy in neurons. Neurobiol Aging 2007; 28:1484-1492.
47. Li S, Yang L, Selzer ME, Hu Y. Neuronal endoplasmic reticulum stress in axon injury and neurodegeneration. Ann Neurol 2013; 74:768-777.
48. Zhang X, Li L, Zhang L, Borowitz JL, Isom GE. Cyanide-induced death of dopaminergic cells is mediated by uncoupling protein-2 up-regulation and reduced Bcl-2 expression. Toxicol Appl Pharmacol 2009; 238:11-19.