Evaluation of Oxidative Stress and DNA Damage in Acromegaly Patients in a Follow-up Study at a Public Tertiary Health Service

Main Article Content

A. C. M. Bonini
C. D. L. Oliveira
L. C. Talon
D. T. Pierine
F. V. Francisqueti
C. R. Correa
V. S. Nunes-Nogueira

Abstract

We evaluated oxidative stress (OS) and DNA damage in acromegaly patients in a follow-up study at a public tertiary health service. Acromegaly patients in follow up at a public tertiary health service from 2012 to 2013 were enrolled in this study. Healthy volunteers were selected as control group. OS was evaluated in plasma and peripheral lymphocytes by determining total antioxidant capacity (TAP), lipophilic antioxidant levels and lipid peroxidation through malondialdehyde (MDA) levels. DNA damage was determined using the comet test. Fifteen acromegaly patients and 19 healthy individuals were included. Considering IGF1 levels<1.3´ the upper limit of the normal range as disease under control, 20% of individuals were uncontrolled for the disease. No significant difference in total carotenoid levels, TAP, or DNA damage was found between groups (respectively, 62.8 and 46, p=0.13; 51.3 and 43.5, p=0.093; 41.4.0 and 47.2, p=0.15). On the other hand, median MDA levels in the acromegaly group was significantly lower than that in the control group (0.44 and 0.977, respectively; p<0.001, Mann-Whitney test). A subgroup comparison within acromegaly patients revealed no statistically significant difference (p>0.05) between those with normal or increased IGF1 levels, with or without metabolic syndrome, or with or without use of statin (0.4 vs. 0.436, 0.42 vs. 0.5 and 0.533 vs, 0.413, respectively). Acromegaly patients when compared with a healthy control group did not present significantly higher levels of OS, antioxidants and DNA damage. However, most patients included in our study achieved disease control.

Keywords:
Acromegaly, oxidative stress, antioxidant, DNA damage, comet test

Article Details

How to Cite
Bonini, A. C. M., Oliveira, C. D. L., Talon, L. C., Pierine, D. T., Francisqueti, F. V., Correa, C. R., & Nunes-Nogueira, V. S. (2020). Evaluation of Oxidative Stress and DNA Damage in Acromegaly Patients in a Follow-up Study at a Public Tertiary Health Service. Asian Journal of Research and Reports in Endocrinology, 3(1), 12-20. Retrieved from https://journalajrre.com/index.php/AJRRE/article/view/30107
Section
Original Research Article

References

Dekkers OM, Biermasz NR, Pereira AM, Romijn JA, Vandenbroucke JP. Mortality in acromegaly: A metaanalysis. The Journal of Clinical Endocrinology and Metabolism. 2008;93(1):61-7.

Orme SM, McNally RJ, Cartwright RA, Belchetz PE. Mortality and cancer incidence in acromegaly: A retrospective cohort study. United Kingdom Acromegaly Study Group. The Journal of Clinical Endocrinology and Metabolism. 1998;83 (8):2730-4.

Kondo T, Hirose M, Kageyama K. Roles of oxidative stress and redox regulation in atherosclerosis. J Atheroscler Thromb. 2009;16(5):532-8.

Ferreira AL, Salvadori DM, Nascimento MC, Rocha NS, Correa CR, Pereira EJ, et al. Tomato-oleoresin supplement prevents doxorubicin-induced cardiac myocyte oxidative DNA damage in rats. Mutation research. 2007;631(1):26-35.

Yeum KJ, Russell RM, Krinsky NI, Aldini G. Biomarkers of antioxidant capacity in the hydrophilic and lipophilic compart-ments of human plasma. Arch Biochem Biophys. 2004;430(1):97-103.

Ralser M, Wamelink MM, Kowald A, Gerisch B, Heeren G, Struys EA, et al. Dynamic rerouting of the carbohydrate flux is key to counteracting oxidative stress. J Biol. 2007;6(4):10.

Aldini G, Dalle-Donne I, Facino RM, Milzani A, Carini M. Intervention strategies to inhibit protein carbonylation by lipoxidation-derived reactive carbonyls. Medicinal Research Reviews. 2007;27(6): 817-68.

Bierhaus A, Hofmann MA, Ziegler R, Nawroth PP. AGEs and their interaction with AGE-receptors in vascular disease and diabetes mellitus. I. The AGE concept. Cardiovasc Res. 1998;37(3):586-600.

Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001;414(6865):813-20.

Bohlooly YM, Carlson L, Olsson B, Gustafsson H, Andersson IJ, Tornell J, et al. Vascular function and blood pressure in GH transgenic mice. Endocrinology. 2001; 142(8):3317-23.

Andersson IJ, Johansson ME, Wickman A, Bohlooly YM, Klintland N, Caidahl K, et al. Endothelial dysfunction in growth hormone transgenic mice. Clinical science (London, England: 1979). 2006;110(2):217-25.

Frick F, Bohlooly YM, Linden D, Olsson B, Tornell J, Eden S, et al. Long-term growth hormone excess induces marked alterations in lipoprotein metabolism in mice. Am J Physiol Endocrinol Metab. 2001;281(6):E1230-9.

Fukuoka H, Iida K, Nishizawa H, Imanaka M, Takeno R, Iguchi G, et al. IGF-I stimulates reactive oxygen species (ROS) production and inhibits insulin-dependent glucose uptake via ROS in 3T3-L1 adipocytes. Growth hormone & IGF research: Official Journal of the Growth Hormone Research Society and the International IGF Research Society. 2010; 20(3):212-9.

Anagnostis P, Efstathiadou ZA, Gougoura S, Polyzos SA, Karathanasi E, Dritsa P, et al. Oxidative stress and reduced antioxidative status, along with endothelial dysfunction in acromegaly. Hormone and metabolic research = Hormon - und Stoffwechselforschung = Hormones et Metabolisme. 2013;45(4):314-8.

Ozkan C, Altinova AE, Cerit ET, Yayla C, Sahinarslan A, Sahin D, et al. Markers of early atherosclerosis, oxidative stress and inflammation in patients with acromegaly. Pituitary. 2015;18(5):621-9.

Aldini G, Yeum KJ, Russell RM, Krinsky NI. A method to measure the oxidizability of both the aqueous and lipid compartments of plasma. Free Radical Biology & Medicine. 2001;31(9):1043-50.

Beretta G, Aldini G, Facino RM, Russell RM, Krinsky NI, Yeum KJ. Total antioxidant performance: A validated fluorescence assay for the measurement of plasma oxidizability. Analytical Biochemistry. 2006;354(2):290-8.

Pierine DT, Navarro ME, Minatel IO, Luvizotto RA, Nascimento AF, Ferreira AL, et al. Lycopene supplementation reduces TNF-alpha via RAGE in the kidney of obese rats. Nutr Diabetes. 2014;4:e142.

Singh NP, McCoy MT, Tice RR, Schneider EL. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res. 1988;175(1):184- 91.

Tice RR, Agurell E, Anderson D, Burlinson B, Hartmann A, Kobayashi H, et al. Single cell gel/comet assay: Guidelines for in vitro and in vivo genetic toxicology testing. Environmental and Molecular Mutagenesis. 2000;35(3):206-21.

Yeum KJ, Taylor A, Tang G, Russell RM. Measurement of carotenoids, retinoids, and tocopherols in human lenses. Invest Ophthalmol Vis Sci. 1995;36(13):2756-61.

Kacmaz A, Polat A, User Y, Tilki M, Ozkan S, Sener G. Octreotide improves reperfusion-induced oxidative injury in acute abdominal hypertension in rats. J Gastrointest Surg. 2004;8(1):113-9.

Nishizawa H, Handayaningsih AE, Iguchi G, Cho Y, Takahashi M, Yamamoto M, et al. Enhanced oxidative stress in GH-transgenic rat and acromegaly in humans. Growth Horm IGF Res. 2012;22(2):64-8.

Bayram F, Bitgen N, Donmez-Altuntas H, Cakir I, Hamurcu Z, Sahin F, et al. Increased genome instability and oxidative DNA damage and their association with IGF-1 levels in patients with active acromegaly. Growth hormone & IGF research: Official Journal of the Growth Hormone Research Society and the International IGF Research Society. 2014; 24(1):29-34.

Bolfi F, Neves AF, Boguszewski CL, Nunes-Nogueira VS. Mortality in acromegaly decreased in the last decade: A systematic review and meta-analysis. European Journal of Endocrinology. 2018; 179(1):59-71.