Biochemical and Metabolomic Changes after Electromagnetic Hyperthermia Exposure to Treat Colorectal Cancer Liver Implants in Rats

Abstract

Background: Hyperthermia (HT) therapy still remains relatively unknown, in terms of both its biological and therapeutic effects. This work aims to analyze the effects of exposure to HT, such as that required in anti-tumor magnetic hyperthermia therapies, using metabolomic and serum parameters routinely analyzed in clinical practice. Methods: WAG/RigHsd rats were assigned to the different experimental groups needed to emulate all of the procedures involved in the treatment of liver metastases by HT. Twelve hours or ten days after the electromagnetic HT (606 kHz and 14 kA/m during 21 min), blood samples were retrieved and liver samples were obtained. 1H-nuclear-magnetic-resonance spectroscopy (1H-NMR) was used to search for possible diagnostic biomarkers of HT effects on the rat liver tissue. All of the data obtained from the hydrophilic fraction of the tissues were analyzed and modeled using chemometric tools. Results: Hepatic enzyme levels were significantly increased in animals that underwent hyperthermia after 12 h, but 10 d later they could not be detected anymore. The metabolomic profile (main metabolic differences were found in phosphatidylcholine, taurine, glucose, lactate and pyruvate, among others) also showed that the therapy significantly altered metabolism in the liver within 12 h (with two different patterns); however, those changes reverted to a control-profile pattern after 10 days. Conclusions: Magnetic hyperthermia could be considered as a safe therapy to treat liver metastases, since it does not induce irreversible physiological changes after application.

Proposal of New Safety Limits for In Vivo Experiments of Magnetic Hyperthermia Antitumor Therapy

“…The proposed combinations of magnetic field intensity and frequency used in this study were established on the basis of previously published work by our own research group in 2016 and 2021 [21]. In those publications, we demonstrated both the therapeutic effectiveness and the non-harmfulness of the procedure; an exposure of twenty-one minutes at 606 kHz and 14 kA/m (8.48 × 10 9 Am −1 s −1 ) induced a 30% destruction of the tumor mass [20], while not leading to irreversible alterations in the biochemical profile and/or metabolomic profile of the animals [21].…”

“…The proposed combinations of magnetic field intensity and frequency used in this study were established on the basis of previously published work by our own research group in 2016 and 2021 [21]. In those publications, we demonstrated both the therapeutic effectiveness and the non-harmfulness of the procedure; an exposure of twenty-one minutes at 606 kHz and 14 kA/m (8.48 × 10 9 Am −1 s −1 ) induced a 30% destruction of the tumor mass [20], while not leading to irreversible alterations in the biochemical profile and/or metabolomic profile of the animals [21]. Due to the modifications implemented in our homemade AMF device used in those previous studies, in the present study it was not possible to adopt exactly the same combination of frequency and intensity, given the new equipment configuration, but rather the most similar combination possible was used (591 kHz and 14 kA/m; 8.27 × 10 9 Am −1 s −1 ).…”

“…Exposures to AMF were performed using a home-made electromagnet previously described by our group [20,21]. The set-up consisted of a solenoid coil 8 cm long, 6 cm in diameter and 9 turns that generated a homogeneous AMF within a volume inside the coil, where the animals were placed (Figure 1).…”

“…In accordance with our previously reported experience, magnetic hyperthermia treatments were performed for 21 min, in the magnetic field shown in Table 1 in the described magnetic hyperthermia configuration. AMF exposure procedures were in accordance with those previously published by our research group [20,21]. Briefly, once the animals were properly anesthetized (intraperitoneal injection of diazepam, ketamine and medetomidine), a middle laparotomy was performed to expose the liver, and two non-resistive fiber optic thermometers OTG-MTK5 (Opsens, Québec, QC, Canada) were located in the animals in order to monitor thermal changes.…”

Electrospun Magnetic Nanofiber Mats for Magnetic Hyperthermia in Cancer Treatment Applications—Technology, Mechanism, and Materials

“…Therefore, two different methods-switching the external magnetic field and changing the direction of the magnetic field-can be used to release this alternative magnetic field for magnetic hyperthermia [117]. Moreover, these lowfrequency alternating magnetic fields (100 kHz-1 MHz) can deeply penetrate the body without causing significant attenuation losses [118][119][120][121]. Alternating magnetic fields with amplitudes of tens of kA/m and frequencies of 100 kHz and 1 MHz are applied in the target area so that the magnetic energy of the magnetic nanomaterials is directed toward the applied magnetic field [122][123][124][125][126].…”