Effects of aspartame on hsp70, bcl-2 and bax expression in immune organs of Wistar albino rats
Arbind Kumar Choudhary, Rathinasamy Sheela Devi
Effects of aspartame on hsp70, bcl-2 and bax expression in immune organs of Wistar albino rats
Aspartame, a ‘first generation sweetener’, is widely used in a variety of foods, beverages, and medicine. The FDA has determined the acceptable daily intake (ADI) value of aspartame to be 50 mg/kg of body weight/day, while the JECFA (Joint FAO/WHO Expert Committee on Food Additives) has set this value at 40 mg/kg of body weight/day. Safety issues have been raised about aspartame due to its metabolites, specifically toxicity from methanol and/or its systemic metabolites formaldehyde and formic acid. The immune system is now recognized as a target organ for many xenobiotics, such as drugs and chemicals, which are able to trigger unwanted apoptosis or to alter the regulation of apoptosis. Our previous studies has shown that oral administration of aspartame (40 mg/kg.bw/day) or its metabolites for 90 days increased oxidative stress in immune organs of Wistar albino rats. In this present study, we aimed to clarify whether aspartame consumption over a longer period (90-days) has any effect on the expression of hsp70, bcl-2 and bax at both mRNA transcript and protein expression levels in immune organs. We observed that oral administration of aspartame for 90 days did not cause any apparent DNA fragmentation in immune organs of aspartame treated animals; however, there was a significant increase in hsp70 expression, apart from significant alteration in bcl-2 and bax at both mRNA transcript and protein expression level in the immune organs of aspartame treated animals compared to controls. Hence, the results indicated that hsp70 levels increased in response to oxidative injury induced by aspartame metabolites; however, these metabolites did not induce apoptosis in the immune organs. Furthermore, detailed analyses are needed to elucidate the precise molecular mechanisms involved in these changes.
aspartame / immune organs / hsp70 / bcl2 / bax
[1] |
Hertelendy ZI, Mendenhall CL, Rouster SD,
Pubmed
|
[2] |
Pohannish RP. Sittig’s handbook of toxic and hazardous chemicals and carcinogens, Noyes/William Andrew, Norwich, NY 2002.
|
[3] |
Tang X, Bai Y, Duong A,
Pubmed
|
[4] |
European Food Safety Authority (EFSA). Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in contact with Food (AFC) on a request from the Commission related to a new long-term carcinogenicity study on aspartame[J]. EFSA J, 2006, 356: 1–44.
|
[5] |
Kotsonis FN, Hjelle JJ. The safety assessment of aspartame:Scientific and regulatory considerations[A], In: Tschanz, C, Butchko HH, Stargel WW. Kotsonis FN (eds), The Clinical Evaluation of a Food Aditive Assessment of Aspartame[M]. CRC Press, Boca Raton FL, 1996; 23–41.
|
[6] |
Stegink LD, Filer LJ Jr, Baker GL. Repeated ingestion of aspartame-sweetened beverage: effect on plasma amino acid concentrations in normal adults[J]. Metabolism, 1988, 37(3): 246–251
Pubmed
|
[7] |
Chew BP, Park JS. Carotenoids Against Disease: Part C: The Immune System and Disease[A]. In: Britton G, Liaanen-Jensen S, Pfander H 9 (eds) Carotenoids: Nutrition and Health[M]. 2009, Germany: Birkhauser Press, 5: 363–382.
|
[8] |
Tortorella D, Gewurz BE, Furman MH,
Pubmed
|
[9] |
Rot A, von Andrian UH. Chemokines in innate and adaptive host defense: basic chemokinese grammar for immune cells[J]. Annu Rev Immunol, 2004, 22: 891–928
Pubmed
|
[10] |
Ogi S, Tanji N, Iseda T,
Pubmed
|
[11] |
Kültz D. Molecular and evolutionary basis of the cellular stress response[J]. Annu Rev Physiol, 2005, 67: 225–257
Pubmed
|
[12] |
DeBiasi RL, Robinson BA, Leser JS,
Pubmed
|
[13] |
Cheng WC, Leach KM, Hardwick JM. Mitochondrial death pathways in yeast and mammalian cells[J]. Biochim Biophys Acta, 2008, 1783(7): 1272–1279
Pubmed
|
[14] |
Adams JM, Cory S. Life-or-death decisions by the Bcl-2 protein family[J]. Trends Biochem Sci, 2001, 26(1): 61–66
Pubmed
|
[15] |
Win-Shwe TT, Yoshida Y, Kunugita N,
Pubmed
|
[16] |
Choudhary AK, Devi RS. Imbalance of the oxidant-antioxidant status by aspartame in the organs of immune system of Wistar albino rats[J]. Afr J Pharm Pharmacol, 2014, 8: 220–230.
|
[17] |
Choudhary AK, Sheela Devi R. Longer period of oral administration of aspartame on cytokine response in Wistar albino rats[J]. Endocrinol Nutr, 2015, 62(3): 114–122
Pubmed
|
[18] |
Choudhary AK, Rathinasamy SD. Aspartame induces alteration in electrolytes homeostasis of immune organs in wistar albino rats[J]. Biomedicine and Preventive Nutrition, 2014, 4: 181–187.
|
[19] |
Choudhary AK, Rathinasamy SD. Effect of long intake of aspartame on ionic imbalance in immune organs of immunized wistar albino rats[J]. Biomedicine and Aging Pathology, 2014, 4: 243–249.
|
[20] |
Gombos K, Varjas T, Orsós Z,
Pubmed
|
[21] |
Makar AB, Tephly TR. Methanol poisoning in the folate-deficient rat[J]. Nature, 1976, 261(5562): 715–716
Pubmed
|
[22] |
Ming H, Wang SY, Craig A. Meadows, Shirley W. Thenen Methotrexate effects on folate status and the deoxyuridine suppression test in rats[J]. Nut Res, 1989, 9: 431–444.
|
[23] |
Rabinowitz JC, Pricer WE. Formiminotetrahydrofolic acid and methenyltetrahydrofolic acid as intermediates in the formation of N10-formyltetrahydrofolic acid[J]. J Am Chem Soc, 1956, 78(21): 5702–5704.
|
[24] |
Feldman S, Conforti N. Participation of the dorsal hippocampus in the glucocorticoid feedback effect on adrenocortical activity[J]. Neuroendocrinology, 1980, 30(1): 52–55
Pubmed
|
[25] |
Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction[J]. Anal Biochem, 1987, 162(1): 156–159
Pubmed
|
[26] |
Pockley AG. Heat shock proteins as regulators of the immune response[J]. Lancet, 2003, 362(9382): 469–476
Pubmed
|
[27] |
Sun L, Chang J, Kirchhoff SR,
Pubmed
|
[28] |
Beere HM, Green DR. Stress management- heat shock protein-70 and the regulation of apoptosis[J]. Trends Cell Biol, 2001, 11(1): 6–10
Pubmed
|
[29] |
Robertson JD, Orrenius S. Molecular mechanisms of apoptosis induced by cytotoxic chemicals[J]. Crit Rev Toxicol, 2000, 30(5): 609–627
Pubmed
|
[30] |
Hunot S, Flavell RA. Apoptosis. Death of a monopoly[J]? Science, 2001, 292(5518): 865–866
Pubmed
|
[31] |
Chipuk JE, Green DR. How do BCL-2 proteins induce mitochondrial outer membrane permeabilization[J]? Trends Cell Biol, 2008, 18(4): 157–164
Pubmed
|
[32] |
Gerl R, Vaux DL. Apoptosis in the development and treatment of cancer[J]. Carcinogenesis, 2005, 26(2): 263–270
Pubmed
|
/
〈 | 〉 |