Modulatory Effects of Aerobic Exercise and Saffron Stigma Extract on Methamphetamine-Induced Histopathological Alterations in the Adrenal Gland of Female Wistar Rats
Subject Areas : New studies in exercise metabolism and physical activityMostafa Mozaffari 1 , somaye rajabi 2 , Sayyed-Javad Ziaolhagh 3
1 - 1. MSc in Exercise Physiology, Islamic Azad University, Shahroud Branch, Shahroud, Iran
2 - Department of Sports Physiology, Islamic Azad University, Shahrood Branch,Shahrood , Iran.
3 -
Keywords: Methamphetamine, Aerobic Training, Saffron, Adrenal Cortex, Histopathology, Zona Fasciculata,
Abstract :
Background: The adrenal glands are key regulators of the stress response through the production of hormones such as cortisol. Methamphetamine (METH), a potent psychostimulant, has been shown to induce structural damage in adrenal tissues. Natural compounds like saffron (Crocus sativus L.) and lifestyle interventions such as aerobic exercise may offer protective or restorative effects. To investigate the impact of aerobic exercise and saffron stigma extract, alone or in combination, on methamphetamine-induced histopathological changes in the adrenal glands of female Wistar rats. Methods: Thirty female Wistar rats were randomly divided into five groups (n=6): (1) control, (2) METH-treated, (3) METH + aerobic exercise, (4) METH + saffron, and (5) METH + aerobic exercise + saffron. Methamphetamine was administered intraperitoneally at 10 mg/kg/day. Aerobic training consisted of treadmill running (25 m/min, 30 minutes/day, 6 days/week) for 4 weeks. Saffron extract (40 mg/kg) was also administered intraperitoneally. Adrenal glands were harvested and processed for histological analysis. Results: METH exposure resulted in significant histopathological damage in all adrenal regions, including zona glomerulosa, fasciculata, reticularis, and the medulla. Both aerobic exercise and saffron extract independently showed partial improvements, while their combination led to a more substantial recovery of adrenal structure. Conclusion: The combination of aerobic exercise and saffron stigma extract exerts synergistic protective effects against METH-induced adrenal damage. These findings suggest a potential therapeutic strategy for managing methamphetamine-related endocrine impairments.
1. Figurasin R, Maguire NJ. 3,4-Methylenedioxy-Methamphetamine Toxicity. StatPearls. Treasure Island (FL): StatPearls Publishing
Copyright © 2022, StatPearls Publishing LLC.; 2022.
2. Wang H, Chen Y, Li X, Wang J, Zhou Y, Zhou C. Moderate-Intensity Aerobic Exercise Restores Appetite and Prefrontal Brain Activity to Images of Food Among Persons Dependent on Methamphetamine: A Functional Near-Infrared Spectroscopy Study. Front Hum Neurosci. 2019;13:400.
3. Sapkota S, David S, Sharma S, Shrestha S, Kalla A. Adrenal infarction secondary to methamphetamine use: a case report and review of the literature. Journal of Medical Case Reports. 2022;16(1):379.
4. Huang J, Zhang R, Wang S, Leung C-K, Yang G, Lin S, et al. Methamphetamine and HIV-tat protein synergistically induce oxidative stress and blood-brain barrier damage via transient receptor potential melastatin 2 channel. Frontiers in Pharmacology. 2021;12:619436.
5. Choromańska B, Myśliwiec P, Kozłowski T, Łuba M, Wojskowicz P, Dadan J, et al. Antioxidant barrier and oxidative damage to proteins, lipids, and DNA/RNA in adrenal tumor patients. Oxidative Medicine and Cellular Longevity. 2021;2021.
6. Tata DA, Yamamoto BK. Interactions between methamphetamine and environmental stress: role of oxidative stress, glutamate and mitochondrial dysfunction. Addiction. 2007;102:49-60.
7. Zhao Y-L, Zhao W, Liu M, Liu L, Wang Y. TBHQ-overview of multiple mechanisms against oxidative stress for attenuating methamphetamine-induced neurotoxicity. Oxidative Medicine and Cellular Longevity. 2020;2020.
8. Kim B, Yun J, Park B. Methamphetamine-induced neuronal damage: neurotoxicity and neuroinflammation. Biomolecules & therapeutics. 2020;28(5):381.
9. Chen L, Ru Q, Xiong Q, Yang J, Xu G, Wu Y. Potential effects of Nrf2 in exercise intervention of neurotoxicity caused by methamphetamine oxidative stress. Oxidative Medicine and Cellular Longevity. 2022;2022.
10. Veisi A, Akbari G, Mard SA, Badfar G, Zarezade V, Mirshekar MA. Role of crocin in several cancer cell lines: An updated review. Iranian journal of basic medical sciences. 2020;23(1):3.
11. Mozaffari S, Yasuj SR, Motaghinejad M, Motevalian M, Kheiri R. Crocin acting as a neuroprotective agent against methamphetamine-induced neurodegeneration via CREB-BDNF signaling pathway. Iranian Journal of Pharmaceutical Research: IJPR. 2019;18(2):745.
12. Joseph DK, Mat Ludin AF, Ibrahim FW, Ahmadazam A, Che Roos NA, Rajab NF. Corrigendum: Effects of aerobic exercise and dietary flavonoids on cognition: a systematic review and meta-analysis. Frontiers in Physiology. 2023;14:1287170.
13. Tokunaga I, Kubo S-i, Ishigami A, Gotohda T, Kitamura O. Changes in renal function and oxidative damage in methamphetamine-treated rat. Legal medicine. 2006;8(1):16-21.
14. Sajadi A, Amiri I, Gharebaghi A, Komaki A, Asadbeigi M, Shahidi S, et al. Treadmill exercise alters ecstasy-induced long-term potentiation disruption in the hippocampus of male rats. Metabolic Brain Disease. 2017;32:1603-7.
15. Panenka WJ, Procyshyn RM, Lecomte T, MacEwan GW, Flynn SW, Honer WG, Barr AM. Methamphetamine use: a comprehensive review of molecular, preclinical and clinical findings. Drug and alcohol dependence. 2013;129(3):167-79.
16. Yamamoto BK, Moszczynska A, Gudelsky GA. Amphetamine toxicities: classical and emerging mechanisms. Annals of the New York Academy of Sciences. 2010;1187(1):101-21.
17. Kita T, Wagner GC, Nakashima T. Current research on methamphetamine-induced neurotoxicity: animal models of monoamine disruption. Journal of pharmacological sciences. 2003;92(3):178-95.
18. Williams MT, Schaefer TL, Furay AR, Ehrman LA, Vorhees CV. Ontogeny of the adrenal response to (+)-methamphetamine in neonatal rats: the effect of prior drug exposure. Stress. 2006;9(3):153-63.
19. Zuloaga DG, Jacobskind JS, Raber J. Methamphetamine and the hypothalamic-pituitary-adrenal axis. Frontiers in neuroscience. 2015;9:178.
20. Zuloaga DG, Johnson LA, Agam M, Raber J. Sex differences in activation of the hypothalamic–pituitary–adrenal axis by methamphetamine. Journal of neurochemistry. 2014;129(3):495-508.
21. Asalgoo S, Tat M, Sahraei H, Pirzad Jahromi G. The psychoactive agent crocin can regulate hypothalamic-pituitary-adrenal axis activity. Frontiers in neuroscience. 2017;11:668.
22. Hashemzaei M, Mamoulakis C, Tsarouhas K, Georgiadis G, Lazopoulos G, Tsatsakis A, et al. Crocin: A fighter against inflammation and pain. Food and Chemical Toxicology. 2020;143:111521.
23. de Araújo FHS, de Barros Primo RB, Olimpio MYM, da Silva NO, Yoshikawa CA, Tanaka LHVB, et al. Changes In Hormonal Response Caused By Different Types Of Physical Exercise: A Literature Review. 2020.
24. Hood DA. Mechanisms of exercise-induced mitochondrial biogenesis in skeletal muscle. Applied Physiology, Nutrition, and Metabolism. 2009;34(3):465-72.
25. Shadegan PA, Khajehlandi A, Mohammadi A. Effect of Aerobic Training and Crocin Consumption on Bax Gene Expression in the Hippocampal Tissue of Ovariectomized Rats. Gene, Cell and Tissue. 2020;7(3).
