The effects of eight weeks of high-intensity interval training and gallic acid supplementation on mTORC1 and ULK1 gene expression in the kidney tissue of cadmium-exposed rats

Zarei, Maryam; Hematfar, Ahmad; Hosseini, Seyed Ali; Sameni, Arash

doi:10.48307/FMSJ.2025.29.4.303

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Volume 29, Issue 4 (Bimonthly 2025)

Feyz Med Sci J 2025, 29(4): 303-315

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The effects of eight weeks of high-intensity interval training and gallic acid supplementation on mTORC1 and ULK1 gene expression in the kidney tissue of cadmium-exposed rats

Maryam Zarei

, Ahmad Hematfar ^*

, Seyed Ali Hosseini

, Arash Sameni

Department of Physical Education and Exercise Science, Bo. C., Islamic Azad University, Borujerd, Iran , ahematfar@yahoo.com

Abstract: (508 Views)

Background and Aim: Cadmium (Cd), a toxic heavy metal, accumulates in the kidney and induces nephrotoxicity by disrupting cellular signaling pathways. The mTORC1 and ULK1 pathways play key roles in balancing protein synthesis and autophagy. This study aimed to evaluate the combined effects of eight weeks of high-intensity interval training (HIIT) and gallic acid (GA) supplementation on the expression of mTORC1 and ULK1 genes in the kidney tissue of rats exposed to cadmium toxicity.
Methods: In this experimental study, 42 male Sprague-Dawley rats were randomly assigned to seven groups (n = 6 per group): healthy control (HC), Cd-exposed (5 mg/kg/day), sham, Cd + GA, Cd + HIIT, Cd + HIIT + GA. GA supplementation groups received 20 mg/kg/day orally for eight weeks. HIIT groups underwent an eight-week training protocol, three sessions per week, at 80–110% VO₂max. At the end of the intervention, mTORC1 and ULK1 gene expression in kidney tissue was measured using real-time PCR.

Results: In the Cd group, mTORC1 expression was significantly decreased (P = 0.001) and ULK1 expression was significantly increased (P = 0.001) compared to the HC group. All intervention groups (Cd + GA, Cd + HIIT, Cd + HIIT + GA) showed significant increases in mTORC1 expression and decreases in ULK1 expression compared to the Cd group (P = 0.001). Moreover, the Cd + HIIT + GA group showed significantly greater mTORC1 expression and lower ULK1 expression compared with both the Cd + GA and Cd + HIIT groups (P = 0.001). In addition, ULK1 expression was significantly lower in the Cd + GA group compared to the Cd + HIIT group (P = 0.004).
Conclusion: The findings indicate that although HIIT and gallic acid supplementation individually mitigate cadmium-induced disruptions in mTORC1 and ULK1 signaling, their combination exerts a stronger synergistic effect. This combination may represent a promising therapeutic strategy to reduce cadmium-induced renal toxicity.

Keywords: High-Intensity Interval Training (HIIT), Gallic acid, Cadmium, Renal toxicity, mTORC1, ULK1, Autophagy admium

Full-Text [PDF 511 kb] (79 Downloads)

Type of Study: Research | Subject: General
Received: 2024/12/9 | Revised: 2025/10/8 | Accepted: 2025/07/30 | Published: 2025/09/29

References

1. Satarug S. Is Chronic Kidney Disease Due to Cadmium Exposure Inevitable and Can It Be Reversed? Biomedicines. 2024; 12(4):718. doi.10.3390/biomedicines12040718 PMid:38672074 PMCid:PMC11048639

2. Abbaszadeh M, Pakdel H, Barakeh S, Pakdel A, et al. Association between cadmium exposure and risk of chronic kidney disease; a systematic review and meta-analysis. J Ren Inj Prev. 2024. doi.10.34172/jrip.2024.32254

3. Liu Y, Lin X, Hao Z, Yu M, Tang Y, Teng X, et al. Cadmium exposure caused cardiotoxicity in common carps (Cyprinus carpio L.): miR-9-5p, oxidative stress, energetic impairment, mitochondrial division/fusion imbalance, inflammation, and autophagy. Fish Shellfish Immunol. 2023;138:108853. doi.10.1016/j.fsi.2023.108853 PMid:37245677

4. Shao Y, Zheng L, Jiang Y. Cadmium toxicity and autophagy: a review. Biometals. 2024; 1-21. doi.10.1007/s10534-023-00581-y PMid:38277035

5. Maskanati F, Ghasemian SO, Khanmohammadi R, Salehi O, et al. Interactive effects of aerobic training and Crocin supplementation on some apoptosis markers in kidney tissue of rats exposed to doxorubicin. Feyz Med Sci J. 2022;26(6):683-90.

6. Kanbay M, Copur S, Yildiz AB, Tanriover C, Mallamaci F, Zoccali C. Physical exercise in kidney disease: A commonly undervalued treatment modality. Eur J Clin Invest. 2024;54(2):e14105. doi.10.1111/eci.14105 PMid:37814427

7. Jafari M, Motamedi P, Khaledi N. The Effect of Chronic Kidney Disease Induction Upon Affective Factors on Muscle Apoptosis in Rats and the Role of Aerobic Training in Its Modulation. Jundishapur Sci Med J. 2021; 20(4): 382-9. doi.10.32598/JSMJ.20.4.2475

8. Azadbakht A, Saremi A. Evaluation of P53 and Nrf2 protein levels in kidney tissue after 8 weeks of endurance training in diabetic rats with morphine withdrawal syndrome. Koomesh. 25(6):647-53.

9. Jokar M, Moghadam MS, Daryanoosh F. The effect of a period of high-intensity interval training on the content of AMPK and PGC-1α proteins in the heart muscle tissue of rats with type 2 diabetes. Daneshvar Med. 2021; 29(1):23-34.

10. Delshad S, Yaghoubi A, Rezaeian N. The Effect of Moderate Intensity Continuous Training on Skeletal Muscle Autophagy Biomarkers in Elderly Male Rats. J North Khorasan Univ Med Sci. 2021;12(4):94-9. doi.10.52547/nkums.12.4.94

11. Roshanfekr H, Edalatmanesh MA, Aghababa H. The effect of gallic acid on oxidative stress parameters and hippocampal cell density in ischemia-renal reperfusion model. Med Sci J Islam Azad Univ Tehran Med Branch. 2022; 32(4):379-88. doi.10.52547/iau.32.4.379

12. Alhazmi AI, El-Refaei MF, Abdallah EAA. Protective effects of gallic acid against nickel-induced kidney injury: impact of antioxidants and transcription factor on the incidence of nephrotoxicity. Ren Fail. 2024; 46(1):2344656. doi.10.1080/0886022X.2024.2344656 PMid:38685608 PMCid:PMC11062283

13. Zhang T, Zhang X, Fei Y, Lu J, Zhou D, Zhang L, et al. Gallic acid suppresses the progression of clear cell renal cell carcinoma through inducing autophagy via the PI3K/Akt/Atg16L1 signaling pathway. Int J Oncol. 2024; 65(1):1-14. doi.10.3892/ijo.2024.5658 PMid:38818827 PMCid:PMC11173374

14. Ojo OA, Rotimi DE, Ojo AB, Ogunlakin AD, Ajiboye BO, et al. Gallic acid abates cadmium chloride toxicity via alteration of neurotransmitters and modulation of inflammatory markers in Wistar rats. Sci Rep. 2023; 13(1):1577. doi.10.1038/s41598-023-28893-6 PMid:36709339 PMCid:PMC9884205

15. Bedford TG, Tipton CM, Wilson NC, Oppliger RA, Gisolfi CV, et al. Maximum oxygen consumption of rats and its changes with various experimental procedures. J Appl Physiol. 1979; 47(6): 1278-83. doi.10.1152/jappl.1979.47.6.1278 PMid:536299

16. Momeni L, Moghadam HF, Hosseini SA, Nikbakht M. Interactive Effects of Endurance Training and Selenium Consumption on the Intrinsic Apoptosis Pathway in the Liver Tissue of Cadmium-Exposed Rats. J Nutr Sci Diet. 2020; 5(3-4):1-9.

17. Ma Y, Su Q, Yue C, Zou H, Zhu J, Zhao H, et al. The effect of oxidative stress-induced autophagy by cadmium exposure in kidney, liver, and bone damage, and neurotoxicity. Int J Mol Sci. 2022; 23(21):13491. doi.10.3390/ijms232113491 PMid:36362277 PMCid:PMC9659299

18. Jung CH, Seo M, Otto NM, Kim DH. ULK1 inhibits the kinase activity of mTORC1 and cell proliferation. Autophagy. 2011; 7(10):1212-21. doi.10.4161/auto.7.10.16660 PMid:21795849 PMCid:PMC3210307

19. Lira VA, Okutsu M, Zhang M, Greene NP, Laker RC, Breen DS, et al. Autophagy is required for exercise training-induced skeletal muscle adaptation and improvement of physical performance. FASEB J. 2013; 27(10):4184. doi.10.1096/fj.13-228486 PMid:23825228 PMCid:PMC4046188

20. Pinto AP, da Rocha AL, Marafon BB, Rovina RL, Muñoz VR, da Silva LECM, et al. Impact of different physical exercises on the expression of autophagy markers in mice. Int J Mol Sci. 2021;22(5):2635. doi.10.3390/ijms22052635 PMid:33807902 PMCid:PMC7962017

21. Guan Y, Zhang M, Lacy C, Shah S, Epstein FH, Yan Z. Endurance Exercise Training Mitigates Diastolic Dysfunction in Diabetic Mice Independent of Phosphorylation of Ulk1 at S555. Int J Mol Sci. 2024;25(1):633. doi.10.3390/ijms25010633 PMid:38203804 PMCid:PMC10779281

22. Hosseinpour Delavar S, Safikhani H, Azizi M. The Effect of Eight Weeks of Continuous and Interval Training with Citrus Aurantium Consumption on Autophagy Markers and MyoD Activation in the Muscle Tissue of Elderly Rats. Elder Health J. 2021; 7(2):71-8.

23. Ahmadvand H, Yalameha B, Adibhesami G, Nasri M, Naderi N, Babaeenezhad E, et al. The protective role of gallic acid pretreatment on renal ischemia-reperfusion injury in rats. Rep Biochem Mol Biol. 2019;8(1):42.

24. Moradi A, Abolfathi M, Javadian M, Heidarian E, Roshanmehr H, Khaledi M, et al. Gallic acid exerts nephroprotective, anti-oxidative stress, and anti-inflammatory effects against diclofenac-induced renal injury in male rats. Arch Med Res. 2021;52(4):380-8. doi.10.1016/j.arcmed.2020.12.005 PMid:33358172

25. Zhou D, Wu Y, Yan H, Shen T, Li S, Gong J, et al. Gallic acid ameliorates calcium oxalate crystal-induced renal injury via upregulation of Nrf2/HO-1 in the mouse model of stone formation. Phytomedicine. 2022;106:154429. doi.10.1016/j.phymed.2022.154429 PMid:36099652

26. Rafiei S, Edalatmanesh MA. The effect of swimming training, Gallic acid and high-fat diet on the serum levels of sex hormones in rats with polycystic ovary syndrome. Feyz Med Sci J. 2018;22(6):564-72.

27. Ranjbar K, Homaie HM, Azarbayjani MA, Piri M. The Effect of Gallic Acid Supplement and Resistance Exercise on the Bio-markers of Liver in Intoxicated Male Rats of Anabolic Steroid. Med Lab J. 2020;14(1):44-9. doi.10.29252/mlj.14.1.44

28. Katoli M, Daloii AA. The effect of boldenone and aerobic training with jujube extract and gallic acid on glutathione peroxidase and catalase in heart tissue of male wistar rats. Tradit Integr Med. 2017;15-23.

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Zarei M, Hematfar A, Hosseini S A, Sameni A. The effects of eight weeks of high-intensity interval training and gallic acid supplementation on mTORC1 and ULK1 gene expression in the kidney tissue of cadmium-exposed rats. Feyz Med Sci J 2025; 29 (4) :303-315
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