Evaluation of Static Electric Field Exposure on Histopathological Structure and Function of Kidney and Liver in DMBA-Induced RAT (Rattus norvegicus Berkenhout, 1769)


  • Luthfi Nurhidayat Laboratorium of Animal Structure and Development, Faculty of Biology, Universitas Gadjah Mada, Yogyakarta, 55281
  • Ibnu Fajar Undergraduate Program, Faculty of Biology, Universitas Gadjah Mada, Yogyakarta, 55281
  • Afif Yati Undergraduate Program, Faculty of Biology, Universitas Gadjah Mada, Yogyakarta, 55281
  • Helmi Hana Prinanda Undergraduate Program, Faculty of Biology, Universitas Gadjah Mada, Yogyakarta, 55281
  • M. Irfan Undergraduate Program, Faculty of Biology, Universitas Gadjah Mada, Yogyakarta, 55281
  • Dalila Afina b Undergraduate Program, Faculty of Biology, Universitas Gadjah Mada, Yogyakarta, 55281
  • Ahmad G. Fadlurrahman Undergraduate Program, Faculty of Biology, Universitas Gadjah Mada, Yogyakarta, 55281
  • Nyoman Yudi Antara Graduate School of Biotechnology, Universitas Gadjah Mada Yogyakarta, 55281
  • Firman Alamsyah Ctech Labs Edwar Technology, Tangerang, Banten, 15320
  • Warsito P. Taruno Ctech Labs Edwar Technology, Tangerang, Banten, 15320
  • Rarastoeti Pratiwi ᶜ Graduate School of Biotechnology, Universitas Gadjah Mada Yogyakarta, 55281; ᵉ Laboratorium of Biochemistry, Faculty of Biology, Universitas Gadjah Mada, Yogyakarta, 55281




Static electric field, liver, kidney, histopathology


Intermediate frequency and low intensity static electric field have been developed for non-invasive cancer therapy nowadays. The evaluation of the vital organs, one of which is kidney and liver, is necessary for pre-clinical safety assessment. This research aimed to evaluate the effect of the intermediate frequency (150 kHz) and low intensity (18 Vpp) static electric fields in kidney tissue of rats induced by DMBA (7,12-Dimethylbenz [α] anthracene). This study was carried out in breast tumor models using Sprague Dawley (SD) rats induced with 7,12-Dimethylbenz [α] anthracene (DMBA) by 20 mg/kg body weight of dose ten times over five weeks. Twenty-four rats were divided into four groups, namely: Non-induction Non-therapy (NINT), Non-Induction Therapy (NIT), Induction Non-Therapy (INT), and Induction Therapy (IT) groups. Static electric field therapy is carried out for 10 hours (resting 2 hours after 5 hours exposure) per day using the Electro-Capacitive Cancer Therapy (ECCT) individual enclosure for 21 days. The blood samples were collected before and after therapy for AST, ALT, and Creatinine measurement. The samples of liver and kidney were processed using Paraffin Method and Hematoxylin-Eosin Staining for histopathological observation. The histopathological score was determined using the ordinal method and post-examination masking. This study reveals that the 150 kHz and 18 Vpp static electric field therapy doesn’t significantly induce histopathological injuries on the liver and the kidney. Furthermore, it also does not have a negative impact on the creatinine, AST, and ALT levels of blood plasma.


F. Bray, J. Ferlay, I. Soerjomataram, R. Siegel, L. Torre, and A. Jemal. (2018). Global Cancer Statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.

E. D. Kirson et al. (2004). Disruption of cancer cell replication by alternating electric fields. Cancer Res., 64(9), 3288-3295. Doi: 10.1158/0008-5472.CAN-04-0083.

F. Alamsyah, I. N. Ajrina, F. Nur, A. Dewi, S. A. Prabandari, and W. P. Taruno. (2015). Antiproliferative effect of electric fields on breast tumor cells in vitro and in vivo, 6(3), 71-77.

M. Giladi et al. (2015). Mitotic spindle disruption by alternating electric fields leads to improper chromosome segregation and mitotic catastrophe in cancer cells. Sci. Rep., 5, 1-16. Doi: 10.1038/srep18046.

F. Alamsyah et al. (2021). Cytotoxic T cells response with decreased CD4/CD8 ratio during mammary tumors inhibition in rats induced by non-contact electric fields. F1000Research, 10, 35. Doi: 10.12688/f1000research.27952.1.

S. E. Abo-Neima, H. A. Motaweh, H. M. Tourk, and M. F. Ragab. (2016). Effects of extremely low frequency electromagnetic fields on kidney functions of albino rats in vivo study. Am. J. Biomed. Sci., 247-258. Doi: 10.5099/aj160400247.

L. I. Khayyat. (2011). The histopathological effects of an electromagnetic field on the kidney and testis of mice.EurAsian J. Biosci., 109, 103-109. Doi: 10.5053/ejobios.2011.5.0.12.

A. K. Petri et al. (2017). Biological effects of exposure to static electric fields in humans and vertebrates: A systematic review. Environ. Heal. A Glob. Access Sci. Source, 16(1), 1-23. Doi: 10.1186/s12940-017-0248-y.

R. Pratiwi et al. (2020). CCL2 and IL18 expressions may associate with the anti-proliferative effect of noncontact electro capacitive cancer therapy in vivo. F1000Research, 8, 1770. Doi: 10.12688/f1000research.20727.2.

J. D. Bancroft and H. C. Cook. (1984). Manual of Histological Techniques. Singapore: Longman Singapore Publisher,

K. N. Gibson-Corley, A. K. Olivier, and D. K. Meyerholz. (2013). Principles for Valid Histopathologic Scoring in Research, 50(6), 1007-1015. Doi: 10.1177/0300985813485099.

H. Gouda and B. Bastia. (2010). Acute renal failure following electrocution. Indian J. Med. Sci., 64(1), 45. Doi: 10.4103/0019-5359.92488.

J. Payne-James, A. Busuttil, and W. Smock. (2003). Forensic medicine: clinical and pathological aspects. Cambridge University Press.

E. D. Kirson et al. (2009). Alternating electric fields (TTFields) inhibit metastatic spread of solid tumors to the lungs. Clin. Exp. Metastasis, 26(7), 633-640. Doi: 10.1007/s10585-009-9262-y.

R. van Schilfgaarde, J. C. Stanley, P. van Brummelen, and E. H. Overbosch. (2012). Clinical Aspects of Renovascular Hypertension, 4. Springer Science & Business Media.

A. I. Dakrory, S. R. Fahmy, A. M. Soliman, A. S. Mohamed, and S. A. M. Amer. (2015). Protective and curative effects of the sea cucumber holothuria atra extract against DMBA-induced hepatorenal diseases in rats.

S. Zare, S. Alivandi, and A. Ebadi. (2007). Histological studies of the low frequency electromagnetic fields effect on liver, testes and kidney in guinea pig. World Applied Sciences Journal, 2(5), 509–511.

R. V Shippee-Rice, S. Fetzer, J. V Long, and A. Armitage. (2011). Gerioperative nursing care: principles and practices of surgical care for the older adult. Springer Publishing Company.

V. Kumar, A. K. Abbas, N. Fausto, and R. Mitchell. (2007). Robbins and cotran pathologic basis of disease, 7th ed. Amsterdam: Elsevier Health Sciences.

J. C. Jennette, V. D. D’Agati, J. L. Olson, and F. G. Silva. (2014). Heptinstall’s Pathology of the Kidney. Lippincott Williams & Wilkins.

E. Cote. (2010). Clinical veterinary advisor-e-book: an excerpt from clinical veterinary advisor 2e-Reprint. Amstermdam: Elsevier Health Sciences.

B. A. Molitoris and M. C. Wagner. (1996). Surface membrane polarity of proximal tubular cells : Alterations as a basis for malfunction. Kidney Int., 49(6), 1592-1597. Doi: 10.1038/ki.1996.231.

W. Haschek, C. Rousseaux, and M. Walling. (2010). Fundamentals of toxicologic : pathology. California: Academic Press Elsevier.

B. Y. E. Ford and C. Huggins. (1963). From the Ben May Laboratory for Cancer Research, The University of Chicago, Chicago, Hydrocarbon-Induced Damage of Testis . --Tuchmann and Demay (4) injected. 5.

R. C. Sills, G. A. Boorman, J. E. Neal, H. L. Hong, and T. R. Devereux. (1999). Mutations in ras genes in experimental tumours of rodents. IARC Sci. Publ., 146, 55-86.

Ö. Lindhe, L. Granberg, and I. Brandt. (2002). Target cells for cytochrome P450-catalysed irreversible binding of 7,12-dimethylbenz[a]anthracene (DMBA) in rodent adrenal glands. Arch. Toxicol., 76(8), 460-466. Doi: 10.1007/s00204-002-0367-1.

B. Di Iorio, S. Torraca, P. Gustaferro, G. Fazeli, and A. Heidland. (2012). High-frequency external muscle stimulation in acute kidney injury (AKI): potential shortening of its clinical course. Clin. Nephrol., 79, 37-45. Doi: 10.5414/CNX77S101.

G. Thakral, J. Lafontaine, B. Najafi, T. K. Talal, P. Kim, and L. A. Lavery. (2013). Wound healing. Diabet Foot Ankle, 1, 1-9. Doi: 10.3402/dfa.v4i0.22081.

M. Brezis, S. Rosen, P. Silva, and F. H. Epstein. (1984). Renal ischemia: A new perspective. Kidney Int., 26(4), 375-383. Doi: 10.1038/ki.1984.185.

B. Trump and S. Chang. (2001). Apoptosis, Oncosis, and Necrosis. Cardiovasc, 146(1), 3-15.

R. J. Park, H. Son, K. Kim, S. Kim, and T. Oh. (2011). The effect of microcurrent electrical stimulation on the foot blood circulation and pain of diabetic neuropathy. J. Phys. Ther. Sci., 23(3), 515-518. Doi: 10.1589/jpts.23.515.

M. C. Moloney, G. M. Lyons, P. Breen, P. E. Burke, and P. A. Grace. (2006). Haemodynamic study examining the response of venous blood flow to electrical stimulation of the gastrocnemius muscle in patients with chronic venous disease. Eur. J. Vasc. Endovasc. Surg., 31(3), 300-305. Doi: 10.1016/j.ejvs.2005.08.003.

T. M. Murad, J. Leibach, and E. Von Haam. (1973). Latent effect of DMBA on adrenal glands of Sprague-Dawley rats: an ultrastructural study. Exp. Mol. Pathol., 18(3), 305-15. http://www.ncbi.nlm.nih.gov/pubmed/4708311.

C. L. Dai et al. (2001). Heat shock protein 72 normothermic ischemia, and the impact of congested portal blood reperfusion on rat liver. World J. Gastroenterol., 7(3), 415. Doi: 10.3748/wjg.v7.i3.415.

R. Wyss, M.; Kaddurah-Daouk. (2000). Creatine and creatinine metabolism. Physiol. Rev., 80(3), 1107-1213.

P. Sokal et al. (2013). Differences in blood urea and creatinine concentrations in earthed and unearthed subjects during cycling exercise and recovery. Evidence-Based Complement. Altern. Med. Doi: 10.1155/2013/382643.

S. L. Delwatta et al. (2018). Reference values for selected hematological, biochemical and physiological parameters of Sprague-Dawley rats at the Animal House, Faculty of Medicine, University of Colombo, Sri Lanka. Anim. Model. Exp. Med., 1(4), 250-254. Doi: 10.1002/ame2.12041.

R. V. Priyadarsini and S. Nagini. (2012). Quercetin suppresses cytochrome P450 mediated ROS generation and NFκB activation to inhibit the development of 7,12-dimethylbenz[a]anthracene (DMBA) induced hamster buccal pouch carcinomas. Free Radic. Res., 46(1), 41-49. Doi: 10.3109/10715762.2011.637204.

B. L. Wei, L. J. Bi, J. Z. Z. Qu, and C. Lin. (2015). Effect of long-term pulsed electromagnetic field exposure on hepatic and immunologic functions of rats, 959-962. Doi: 10.1007/s00508-015-0732-8.

E. G. Kıvrak, K. K. Yurt, A. A. Kaplan, and G. Altun. (2019). Effects of electromagnetic fields exposure on the antioxidant defense system. 5, 167-176. Doi: 10.1016/j.jmau.2017.07.003.

Y. Mandel, R. Dalal, P. Huie, U. States, and J. Wang. (2013). Vasoconstriction by electrical stimulation : new approach to control. Doi: 10.1038/srep02111.

C. C. Leung and K. K. Young. (2018). Clinical aspects of hepatic disease. Anaesth. Intensive Care Med., 19(1), 4-6. Doi: 10.1016/j.mpaic.2017.10.009.

C. Petterino and A. Argentino-Storino. (2006). Clinical chemistry and haematology historical data in control Sprague-Dawley rats from pre-clinical toxicity studies. Exp. Toxicol. Pathol., 57(3), 213-219. Doi: 10.1016/j.etp.2005.10.002.

M. Jamal, O. Worsfold, T. McCormac, and E. Dempsey. (2009). A stable and selective electrochemical biosensor for the liver enzyme alanine aminotransferase (ALT). Biosens. Bioelectron., 24(9), 2926-2930. Doi: 10.1016/j.bios.2009.02.032.

P. Y. Kwo, S. M. Cohen, and J. K. Lim. (2017). ACG clinical guideline: evaluation of abnormal liver chemistries. Am. J. Gastroenterol., 112(1), 18-35. Doi: 10.1038/ajg.2016.517.

X. Gao, Y. Zeng, S. Liu, and S. Wang. (2013). Acute stress show great influences on liver function and the expression of hepatic genes associated with lipid metabolism in rats. Lipids Health Dis., 12, 118. Doi: 10.1186/1476-511X-12-118.

B. Jansson. (2019). Potassium, sodium, and cancer: a review. J. Environ. Pathol. Toxicol. Oncol., 15(2-4), 65-73. http://europepmc.org/abstract/med/9216787.

M. Barisic and H. Maiato. (2016). The mitotic spindle. Encyclopedia of Cell Biology, 637-648.

C. Cebra, R. J. Van Saun, D. E. Anderson, A. Tibary, and L. R. W. Johnson. (2013). Llama and Alpaca Care: Medicine, Surgery, Reproduction, Nutrition, and Herd Health: First Edition.