Journal of Isfahan Medical School

Journal of Isfahan Medical School

The Effect of Eight Weeks of Aerobic Training Combined with Gallic Acid Consumption on Changes in Caspase 3 and miR-21 in Kidney Tissue of Rats Exposed to Cadmium

Document Type : Original Article (s)

Authors
1 Department of Sports Physiology, Maha.C., Islamic Azad University, Mahallat, Iran
2 Department of Physical Education, North Tehran Branch, Islamic Azad University, Tehran, Iran
3 Faculty of Physical Education, Tolo Mehr University of Qom, Qom, Iran
10.48305/jims.v44.i872.1375
Abstract
Background: Cadmium (Cd) is a toxic heavy metal that can cause irreversible tissue damage, particularly in the kidneys. Although exercise and antioxidants have been reported to exert protective effects against renal disorders, the combined effects of aerobic training (AT) and gallic acid (GA) remain unclear. Therefore, this study investigated the effects of eight weeks of AT combined with GA supplementation on caspase-3 and miR-21 expression in the kidney tissue of Cd-exposed rats.
Methods: Forty-two male Sprague–Dawley rats (8–9 months old, 250–270 g) were randomly assigned to healthy control (HC), Cd, sham, Cd+GA, Cd+AT, and Cd+AT+GA groups. GA was administered orally at 20 mg/kg/day. The exercise groups performed treadmill running for eight weeks, three sessions/week, at 15 m/min and a 15° incline, with session duration progressively increased from 15 to 60 min. Data were analyzed using One-way ANOVA with Tukey’s post hoc test and two-way ANOVA with Bonferroni correction.
Findings: Compared with HC, the Cd group showed higher caspase-3 and lower miR-21 expression (P = 0.001). Exercise and GA significantly reduced caspase-3 expression (P = 0.001), with a significant exercise×GA interaction (P = 0.001). Both exercise and GA significantly increased miR-21 expression (P = 0.001), with a significant interaction effect (P = 0.001).
Conclusion: Exercise and GA were associated with reduced caspase-3 and increased miR-21 expression in Cd-exposed rats, suggesting potential modulation of apoptotic responses.

Highlights

Bahram Abedi: Google Scholar

Keywords
Subjects

1.     Yan LJ, Allen DC. Cadmium-induced kidney injury: oxidative damage as a unifying mechanism. Biomolecules 2021; 11(11): 1575.
2.     Klaassen CD, Liu J, Choudhuri S. Metallothionein: an intracellular protein to protect against cadmium toxicity. Annu Rev Pharmacol Toxicol 1999; 39(1): 267–94.
3.     Thévenod F, Lee WK. Live and let die: roles of autophagy in cadmium nephrotoxicity. Toxics 2015; 3(2): 130–51.
4.     Song N, Zhang T, Xu X, Lu Z, Yu X, Fang Y, et al. miR-21 protects against ischemia/reperfusion-induced acute kidney injury by preventing epithelial cell apoptosis and inhibiting dendritic cell maturation. Front Physiol 2018; 9: 790.
5.     Huang R, Ding L, Ye Y, Wang K, Yu W, Yan B, et al. Protective effect of quercetin on cadmium-induced renal apoptosis through cyt-c/caspase-9/caspase-3 signaling pathway. Front Pharmacol 2022; 13: 990993.
6.     Davari F, Alimanesh Z, Alimanesh Z, Salehi O, Hosseini SA. Effect of training and crocin supplementation on mitochondrial biogenesis and redox-sensitive transcription factors in liver tissue of type 2 diabetic rats. Arch Physiol Biochem 2022; 128(5): 1215–20.
7.     Ghosh S, Khazaei M, Moien-Afshari F, Ang LS, Granville DJ, Verchere CB, et al. Moderate exercise attenuates caspase-3 activity, oxidative stress, and inhibits progression of diabetic renal disease in db/db mice. Am J Physiol Renal Physiol 2009; 296(4): F700–F708.
8.     Azizi S, Saghebjoo M, Mohiti- Ardakani J. Reducing effects of aerobic exercise training combined with berberine chloride supplementation on the apoptotic markers of kidney in streptozotocin-induced diabetic male rats. Middle East J Rehabil Health Stud 2019; 6(4): e96483. .
9.     Delshad A, Salimi F, Valipour S. The effect of physical activity along with the consumption of hydroalcoholic extract of date pollen on the expression of some microRNAs in cadmium-induced toxicity in rat kidney tissue [in Persian]. Med J Tabriz Uni Med Sci 2024; 46(2): 165-74.
10.  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 [in Persian]. Feyz Med Sci J 2025; 29(4): 303–15.
11.  Zahedi F, Kowsar R, Khodabandeh Z, Dara M, AlaeeS. Protective effects of gallic acid against lead acetate‐induced toxicity in mice ovary: focus on apoptosis, inflammation, and folliculogenesis. Food Sci Nutr 2025; 13(7): e70638.
12.  Gelen V, Sengul E, Yildirim S, Cinar I. The role of GRP78/ATF6/IRE1 and caspase-3/Bax/Bcl2 signaling pathways in the protective effects of gallic acid against cadmium-induced liver damage in rats. Iran J Basic Med Sci 2023; 26(11): 1326-33.
13.  Alhazmi AI, El-Refaei MF, Abdallah EA. 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.
14.  Lee AT, Yang MY, Tsai IN, Chang YC, Hung TW, Wang CJ. Gallic acid alleviates glucolipotoxicity-induced nephropathy by miR-709-NFE2L2 pathway in db/db mice on a high-fat diet. J Agric Food Chem 2024; 72(41): 22645–60.
15.  Moghtaderi H, Sepehri H, Delphi L, Attari F. Gallic acid and curcumin induce cytotoxicity and apoptosis in human breast cancer cell MDA-MB-231. Bioimpacts 2018; 8(3): 185-94.
16.  Momeni L, Fathi Moghadam H, Hosseini S, 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).
17.  Ojo AO, Rotimi DE, Ojo AB, Ogunlakin AD, Ajiboye BO. Gallic acid abates cadmium chloride toxicity via alteration of neurotransmitters and modulation of inflammatory markers in Wistar rats. Sci Rep 2023; 13(1): 1577.
18.  McCullough DJ, Nguyen LMD, Siemann DW, Behnke BJ. Effects of exercise training on tumor hypoxia and vascular function in the rodent preclinical orthotopic prostate cancer model. J Appl Physiol 2013; 115(12): 1846–54.
19.  Jiaxin S, Shengchen W, Yirong C, Shuting W, Shu L. Cadmium exposure induces apoptosis, inflammation and immunosuppression through CYPs activation and antioxidant dysfunction in common carp neutrophils. Fish Shellfish Immunol 2020; 99: 284–90.
20.  Mollajan E, Yazdani S, Ghasemzadeh M. miR-21 in cardiovascular disease: new insights and emerging therapeutic potential. Discov Appl Sci 2025; 7(5): 447.
21.  Alipour Ghazichaki N, Torabi Pelet Kale G, Hosseini SA, Noori F, Fallah M, Abdi A, et al. Curcumin and aerobic training mitigate cadmium-induced oxidative stress and apoptosis via miR-21 and miR-133 modulation in the rat hippocampus. Neurol Res 2026; 48(7): 941-56.
22.  de Lima WV, Visona I, Schor S, Almeida WS. Preconditioning by aerobic exercise reduces acute ischemic renal injury in rats. Physiol Rep 2019; 7(14): e14176.
23.  Improta Caria AC, Vasques Nonaka CK, Pereira CS, Pereira Soares MB, Macambira SG, de Freitas Souza BS. Exercise training-induced changes in microRNAs: beneficial regulatory effects in hypertension, type 2 diabetes, and obesity. Int J Mol Sci 2018; 19(11): 3608.
24.  Nazanin M, Tolouei‐Azar J, Razi M. Running exercise training‐induced impact on oxidative stress and mitochondria‐related apoptosis in rat's testicles. Andrologia 2022; 54(9): e14520.
25.  Afzal M, Greco F, Quinzi F, Scionti F, Maurotti S, Montalcini T, et al. The effect of physical activity/exercise on miRNA expression and function in non-communicable diseases—a systematic review. Int J Mol Sci 2024; 25(13): 6813.
26.  Agahi MRH, Mosallanejad Z, Salehi OR. The effects of resistance training and spirulina on the performance of the antioxidant system with emphasis on mir125b, mir146a and cognitive function in stanazolol-induced neurotoxicity in rats. Chem Biol Interact 2022; 366: 110112.
27.  Eslamifar Z, Moridnia A, Sabbagh S, Ghaffaripour R, Jafaripour L, Behzadifard M. Ameliorative effects of Gallic acid on cisplatin‐induced nephrotoxicity in rat variations of biochemistry, histopathology, and gene expression. Biomed Res Int 2021; 2021(1): 2195238.
28.  Obafemi TO. Ameliorate Electrolyte Imbalances in AlCl3‐Induced Nephrotoxicity in Wistar Rats. Biochem Res Int 2022; 2022(1): 6151684.
29.  Hussein RM, Anwar MM, Farghaly HS, Kandeil MA. Gallic acid and ferulic acid protect the liver from thioacetamide-induced fibrosis in rats via differential expression of miR-21, miR-30 and miR-200 and impact on TGF-β1/Smad3 signaling. Chem Biol Interact 2020; 324: 109098.
30.  Paolini A, Curti V, Pasi F, Mazzini G, Nano R, Capelli E. Gallic acid exerts a protective or an anti-proliferative effect on glioma T98G cells via dose-dependent epigenetic regulation mediated by miRNAs. Int J Oncol 2015; 46(4): 1491–7.
31.  Hajimoradi M, Fazilati M, Gharib-Naseri MK, Sarkaki A. Gallic acid and exercise training improve motor function, nerve conduction velocity but not pain sense reflex after experimental sciatic nerve crush in male rats. Avicenna J Phytomed 2015; 5(4): 288-97.
32.  Akbari M, Moradi L, Alizadeh R, Abbasi Daloii A. Investigating the effects of endurance training and gallic acid on Annexin-5 and caspase-3 of cardiac tissue in male wistar rats undergoing boldenone [in Persian]. Complement Med J 2018; 8(2): 2279–92.
33.  Zhao XL, Cao ZJ, Li KD, Tang F, Xu LY, Zhang JN, et al. Gallic acid: A dietary metabolite’s therapeutic potential in the management of atherosclerotic cardiovascular disease. Front Pharmacol 2025; 15: 1515172.
34.  Vakili J, Ghale Gir S, Khani M, Azali Alamdari K. The effect of Eight Weeks High- Intensity Interval Training (HIIT) on the Expression of miRNA-21 and miRNA-1 in Diabetic Male Rats [in Persian]. Pejouhesh dar Pezeshki 2022; 46(4): 99-110.
Volume 44, Issue 872
4th Week, September
September and October 2026
Pages 1375-1383

  • Receive Date 27 June 2026
  • Accept Date 13 September 2026