Mycotoxins, Mitochondria, and Electromagnetic Radiation — The Melatonin Connection

Why is exposure to toxic mold becoming a major health concern for many individuals? Compared to sanitary conditions hundreds or perhaps thousands of years ago, modern hygiene, advanced technology in food processing, storage, and handling should offer a higher degree of protection against contamination and exposure to natural toxins. Yet effects of mold toxicity are widespread and many individuals suffer from various health issues that may involve the immune, pulmonary, intestinal, cardiovascular, hematological, lymphatic, nephropathic, and neurological systems. 

It is reasonable to assume that humans have always been challenged by mold toxicity; so why has it only become a problem in the past several decades? 

What are Mycotoxins?

Mycotoxins are small molecules produced by fungi or molds that contaminate agriculture products. Mycotoxins are commonly found in cereals, nuts, and seed oils, as well as in foods of animal origin, such as milk and milk derivatives, eggs and meat, when the source animals are fed contaminated fodder [1]. Mycotoxins such as aflatoxins, gliotoxin, ochratoxin A, and deoxynivalenol can contaminate food and exert detrimental effects on human health.

Super Toxic T-2 Trichothecenes is a Known Bioweapon

There is a type of extremely toxic mycotoxin called trichothecene produced by a variety of fungi, one being the S chartarum, which is an extremely common black mold that can grow on natural and artificial substrates including common building materials typically found indoors in residential and commercial buildings [19]. Trichothecenes are extremely toxic because they are potent inhibitors of protein synthesis in eukaryotes, including humans. This class of toxins can easily penetrate cell membranes and target rapidly dividing cells in bone marrow and gastrointestinal tracts [2]. 

Type A trichothecenes class T-2 mycotoxins produced by various fungi exert toxicity at such high levels that this toxin is the only known mycotoxin produced by fungi used as a bio-weapon [3]. 

T-2 Multiple Cytotoxic Effects

T-2 toxin is able to modulate the immune system by either inhibiting or superinducing both interleukin and mRNA levels in CD4+ T-cells [4]. Trichothecenes also disrupt hematopoietic systems and organs such as bone marrow and spleen [5, 6]. 

T-2 and Mycotoxins are Toxic to Heme

In animal studies that tested mycotoxin effects, T-2 trichothecene toxin was found to significantly suppress hematological functions. RBC and WBC reductions were observed in all groups exposed to mycotoxins. T-2 treated groups showed the most severe toxicity compared to other mycotoxin treated groups. In the presence of mycotoxins, granulocytes, lymphocytes, B cells, and platelets all showed significant reductions to different degrees [7]. 

Mycotoxins Bind to AChE, CYP450 and DNA to Cause Cytotoxicity

Human acetylcholinesterase (AChE) is an enzyme that is essential for neurological transmission. Mycotoxins like aflatoxin and T-2 trichothecenes can bind to AChE to cause neurological dysfunctions [8, 9]. Cytochrome p450 is a heme-thiolate protein responsible for the metabolism of drugs, xenobiotics, and endogenous substrates including melatonin [11]. 

T-2 and other mycotoxins, through binding to acetylcholinesterase (AChE) and cytochrome P450 receptors can significantly alter their functions, leading to carcinogenesis, teratogenesis, hepatotoxicity, nephrotoxicity, immunotoxicity and neurotoxicity. Studies now find associations between mycotoxins and neurodevelopmental disorders such as autism spectrum disorder [12]

DNA is the known target of mycotoxins after they are metabolized in the liver by cytochrome p450 enzymes. Binding to DNA creates a covalent adduct that leads to a carcinogenic lesion [13]. The cytotoxic effects of mycotoxins were first reported over 30 years ago when Thompson and Wannemacher demonstrated the in vivo inhibition of protein and DNA synthesis in rodents [14]. DNA damage from mycotoxin is an early event associated with the generation of reactive oxygen species (ROS) and lipid peroxidation.

Mycotoxins Can Cause Cancer by Suppressing p53 

A systematic literature review of epidemiological studies was able to find associations between mycotoxins and cancer development in humans; the cancers studied included liver, breast, and cervical cancer [15]. The mechanisms used by mycotoxins to activate tumorigenesis may be the modulation of gene expression and transcription via epigenetic processes such as methylation. A recent in vitro study demonstrated that the mycotoxin fusaric acid was able to inhibit expression of the important p53 tumor suppressor protein by inducing hypermethylation of its promoter [16]. 

T-2 Elevates Oxidative Stress in Mitochondria 

Trichothecenes are known to cause oxidative stress in mitochondria in a dose-dependent manner [17]. T-2 causes depolarization of mitochondria membranes resulting in mitochondrial membrane fragmentation in yeast models. This decrease in membrane potential results in a corresponding increase in reactive oxygen species [18]. Yeast with high sensitivity to trichothecenes exhibited higher levels of oxidative stress with increased ROS in mitochondria [18].  Yeast can increase their tolerance to trichothecene toxicity by enhancing degradation pathways known as mitophagy. By activating mitophagy, cells can efficiently eliminate mitochondria damaged by mycotoxins and reduce mitochondria oxidative stress levels [17]. 

Mycotoxins Can Cause Cell Death 

The S. chartarum mold that thrives in damp buildings produces another trichothecene mycotoxin called satratoxin, in addition to T-2. Exposure to satratoxin has been found to cause apoptosis of olfactory sensory neurons (OSNs) in the olfactory epithelium [20]. Satratoxin mold can trigger programmed cell death by activating apoptotic signaling pathways including caspase-3 [21, 22]; p38 MAPK [23, 24], and ERK [25, 26]

Potential Long-term Effects from Lipid Peroxidation from T-2 Poisoning

As early as 1989, evidence showed that T-2 poisoning even in extremely small concentrations could induce significant lipid peroxidation [27]. Prolonged exposure to these mycotoxins even in minute subtoxic levels could potentially result in long-term health consequences as a result of systemic lipid peroxidation in plasma membranes. Low-level lipid peroxidation can cause membrane permeability that allows solutes and other molecules to permeate across lipid bilayers in plasma membranes [28]. The translocation of small nanoparticles is also enhanced when there is lipid peroxidation in membranes [29].

In the normal physiological or pathological environments, lipid peroxidation levels are usually quite low due to the presence of endogenous antioxidants like melatonin, as well as saturated fatty acids that are not susceptible to peroxidation [30]. However, consistent exposures to mycotoxins can induce systemic low-level lipid peroxidation that alters the structural formation of plasma membranes, making them more permeable to solutes [28]. 

Membrane integrity is essential for cell survival. Structural damages to membranes from lipid peroxidation can cause membrane-related diseases including diabetes and obesity [31], red blood cell abnormalities [32], multiple sclerosis [33], muscular dystrophy [34], Crohn’s Disease[35], and even rheumatoid arthritis to name a few [36]. 

T-2 Toxin is a Radiomimetic Compound

Radiomimetics are drugs that elicit effects similar to radiation exposure. These pharmaceuticals are often used in chemotherapies to treat cancer. Animals exposed to T-2 trichothecenes would show ‘radiomimetic’ shock-like effects that may include diarrhea, vomiting, leukocytosis and hemorrhage. Higher doses would often result in the death of these lab animals [37, 38]. Chronic exposure to trichothecenes can exacerbate the effects of ionizing radiation. In addition, electromagnetic radiation ubiquitously present in our environment may enhance the toxicity of mycotoxins such as T-2 trichothecene. 

Electromagnetic Radiation 

Compelling evidence supports the theory that electromagnetic field (EMF) exposure can affect health by modulating redox-related processes in mitochondria to cause extensive leakage of electrons in mitochondrial complexes responsible for oxidative phosphorylation during the generation of ATP energy. The leaked electrons from EMF exposure could be the major source of ROS and increased oxidative stress [39].

Proton leakage in mitochondria is the major source of the superoxide ROS, while increased ROS can cause more electron leakage. Hence, ROS in mitochondria has the potential to become a self-reinforcing positive feedback loop that causes disease in various tissues and organs. Mitochondria isolated from hearts of patients with ischaemia/reperfusion injury showed significantly higher rates of proton leakage [40]. 

EMF has been shown in many studies to activate voltage-gated calcium channels (VGCCs) [41], however, the effects of VGCC activation appear to be controversial as some studies showed negative effects while others showed positive effects [41]. The reason for these discrepancies may be due to the fact that membranes, especially mitochondrial membranes, may respond differently to different intensities and frequencies of EMF [42]. Regardless, one common mechanism underlies all EMF effects on cell membranes.

EMF Causes Membrane Depolarization

Calcium ion movement across voltage‐gated calcium channels (VGCCs) is ALWAYS preceded by membrane depolarization. Depolarization opens VGCCs allowing ion movements across the channels [43]. In cells and mitochondria, depolarization of the membrane causes loss of  membrane potential (ΔΨm), where the membrane charge state changes from a negative to a positive one. This change has a direct impact on the ability of mitochondria to produce energy because the collapse of the membrane potential causes protons to leak back into the matrix instead of being driven through the ATP synthase, rotating the synthase in the process [44]. 

By causing proton leakage, membrane depolarization can increase ROS and oxidative stress in mitochondria [45]. The inability to repolarize plasma membranes, or the sustained depolarization of membranes, may result in energy depletion in mitochondria, as well as increased ROS leading to apoptosis [46]. 

900 MHz frequency has been observed to cause apoptosis and oxidative stress via mitochondrial depolarization in breast cancer cells [47].  Another experiment found mice exposed to 900 MHz produced extensive DNA damage and cell cycle arrest in testicular germ cells as a result of mitochondria membrane depolarization that destabilized cellular redox homeostasis [48]. Studies discovered that 900 MHz could modulate surface charge distribution, changing the orientation of hydrophilic phospholipids in plasma membranes [49]. 

EMF May Enhance Cytotoxicity of Mycotoxins

The ability of EMF to alter lipid membrane dynamics is similar to how mycotoxins cause membrane damage via increased lipid peroxidation from oxidative stress. Magnetic fields have been demonstrated to increase ROS in  human, mouse, rat cells, and tissues [50]. Lipid bilayers of membranes exhibiting peroxidation showed conformational changes in the lipids, resulting in membrane permeability that eventually damage cell membranes [51]. What is also interesting is that lipid peroxidation can also activate ion channels that result in membrane depolarization, similar to effects from exposure to  EMF [52]. 

It is becoming quite clear that cytotoxicity of mycotoxins are reinforced and exacerbated by EMF, while the damage from EMF can be increased significantly from exposure to mycotoxins. This positive feedback between EMF and mycotoxins is further exacerbated by the depletion of the important ancient molecule melatonin, as a result of suppression by light at night [53], as well as constant exposure to man-made magnetic fields such as electricity [54]. 

Melatonin is Your Best Friend Against Mycotoxins

Different in vitro and in vivo studies have reported melatonin to be an effective protective agent against toxicity induced by mycotoxins [55-57].  How does melatonin accomplish this remarkable feat? Very simply, melatonin can attenuate ALL the damages exerted by various mycotoxins. Take a look at the following diagrams showing how melatonin can suppress pathways activated by different mycotoxins.

[Source: Milad Iranshahy, Leila Etemad, Abolfazl Shakeri, et al. Protective activity of melatonin against mycotoxins-induced toxicity: a reviewToxicological & Environmental Chemistry Volume 101, 2019 – Issue 9-10  DOI: 10.1080/02772248.2020.1731751]

[Source: Milad Iranshahy, Leila Etemad, Abolfazl Shakeri, et al. Protective activity of melatonin against mycotoxins-induced toxicity: a reviewToxicological & Environmental Chemistry Volume 101, 2019 – Issue 9-10  DOI: 10.1080/02772248.2020.1731751]


[Source: Milad Iranshahy, Leila Etemad, Abolfazl Shakeri, et al. Protective activity of melatonin against mycotoxins-induced toxicity: a reviewToxicological & Environmental Chemistry Volume 101, 2019 – Issue 9-10  DOI: 10.1080/02772248.2020.1731751]

Melatonin Inhibits Lipid Peroxidation Induced by Oxidative Stress

Melatonin is a potent scavenger of free radicals. Its ability to prevent lipid peroxidation was clearly elucidated more than two decades ago. An in vivo experiment on animals with organ damage induced by lipid peroxidation from ethanol free radical oxidative stress revealed that melatonin supplementation significantly reversed lipid peroxidation to protect brains, hearts, lungs and testes from ethanol toxicity. In fact, melatonin treatment rescued tissue lipid peroxidation and returned levels to those of control animals [58]. 

Melatonin Enhances Mitophagy and Modulates Apoptosis Signaling Pathways

Mycotoxins and EMF can damage mitochondria. In yeast models, cells with enhanced mitophagy showed higher resistance against toxic effects of mycotoxins [17]. In vitro studies demonstrated that melatonin is able to upregulate mitophagy in mitochondria and prolong cell survival under conditions of oxidative stress [59]. Mitochondria targeted by Trichothecenes mycotoxins are challenged by increased oxidative stress, but effective degradation of mitochondria damaged by mycotoxins via mitophagy can increase cell survival [17].  

Various mycotoxins, including satratoxin can trigger programmed cell death by activating apoptotic signaling pathways including caspase-3 [21, 22]; p38 MAPK [23, 24], and ERK [25, 26].  Melatonin is a potent modulator of apoptotic signaling pathways. In rodents with diabetic retinopathy, melatonin was found to suppress the MAPK signaling pathway to inhibit inflammation and apoptosis [60]. Melatonin was also found to maintain the activation of the ERK MAPK survival pathway to counter apoptosis triggered by UVB damage in vitro [61].

Melatonin Protects DNA from Damage by Increasing p53 Tumor Suppressor

DNA is the known target of mycotoxins after they are metabolized in the liver by cytochrome p450 enzymes. Binding to DNA creates a covalent adduct that leads to a carcinogenic lesion [13]. Melatonin is well known as an anticancer agent. High levels of melatonin can prevent cells from malignant development. Melatonin can prevent DNA damage accumulation and cell proliferation in  tumorigenesis by activating p53 tumor suppressor pathways via phosphorylation of p53 [62]. 

Yet the most exciting discovery in the study of melatonin and mycotoxins is the work by Maroli published in 2020 [63]. 

Melatonin Inhibits T-2 Toxicity by Competitive Binding to AChE and CYP450

Mycotoxins bind to AChE and CYP450 to cause detrimental health effects. Mycotoxins like aflatoxin and T-2 trichothecenes can bind to AChE resulting in various neurological dysfunctions [8, 9]. T-2 and other mycotoxins, through binding to acetylcholinesterase (AChE) and cytochrome P450 receptors can significantly alter their functions, leading to carcinogenesis, teratogenesis, hepatotoxicity, nephrotoxicity, immunotoxicity and neurotoxicity.

Maroli definitively showed that melatonin can bind to both acetylcholinesterase (AChE) and CYP450 with greater affinity and stability than the super toxic T-2 trichothecene [63]. That means if there is adequate melatonin present, the molecule can prevent mycotoxins from binding to important enzymes and receptors to cause significant damage and oxidative stress.  The chart below shows that the negative free energy is greater when melatonin binds to AChE and CYP450 compared to mycotoxins. A greater negative free energy = more efficient binding and stability.

Take a look at the diagrams “a” to “d” below.

Diagrams a, b, show the exact binding locations of melatonin and mycotoxin T-2 trichothecene in AChE, respectively. 

Diagrams c, d show the binding locations of melatonin and mycotoxin T-2 trichothecene in CYP450, respectively. 

[Source: Nikhil Maroli Melatonin Protects T-2 toxin-induced neuronal stress through Acetylcholinesterase & Cytochrome P450 receptor-mediated signaling bioRxiv preprint doi:]

The diagrams above imply that if melatonin occupies the same binding positions but with higher stability and affinity than T-2, then T-2 will be blocked from binding to these important enzymes and receptors to cause cytotoxicity. This is probably the most exciting discovery in the field of mycotoxin treatment by natural small molecules.

Melatonin is an ancient molecule that has evolved with living systems for more than 3 billion years. It has not failed to protect living organisms from endogenous and exogenous stress, and will continue to do so given the opportunity. Our light environment at night strongly suppresses melatonin production. Together with increased oxidative stress from constant EMF exposure, exogenous melatonin supplementation may be required to support deficiencies. It is time for melatonin to gain wide acceptance across all health disciplines as it is truly a miraculous molecule.

Have you had your AA and MEL today?


[1] Bryden, W. L. Mycotoxin contamination of the feed supply chain: Implications for animal productivity and feed security. Anim. Feed Sci. Technol. 173, 134–158 (2012).

[2] Feinberg B, McLaughlin CS. Biochemical mechanism of action of trichothecene mycotoxins. In: Beasley VR, editor. Trichothecene Mycotoxicosis: Pathophysiologic Effects. Vol. 1. Boca Raton: CRC Press; 1989. pp. 27–35.

[3] Venkataramana M., Chandranayaka S., Prakash H.S., Niranjana S.R. (2015) Mycotoxins Relevant to Biowarfare and Their Detection. In: Gopalakrishnakone P., Balali-Mood M., Llewellyn L., Singh B.R. (eds) Biological Toxins and Bioterrorism. Toxinology. Springer, Dordrecht.

[4] Ouyang YL, Azcona-Olivera JI, Pestka JJ. Effects of trichothecene structure on cytokine secretion and gene expression in murine CD4+ T-cells. Toxicology. 1995 Dec 15;104(1-3):187-202. doi: 10.1016/0300-483x(95)03147-8. PMID: 8560498.

[5] Obremski K, Podlasz P, Żmigrodzka M, Winnicka A, Woźny M, Brzuzan P, Jakimiuk E, Wojtacha P, Gajęcka M, Zielonka L, Gajęcki M. The effect of T-2 toxin on percentages of CD4+, CD8+, CD4+CD8+ and CD21+ lymphocytes, and mRNA expression levels of selected cytokines in porcine ileal Peyer’s patches. Pol J Vet Sci. 2013;16:341–349.

[6] Froquet R, Arnold F, Batina P, Parent-Massin D. Do trichothecenes reduce viability of circulating blood cells and modify haemostasis parameters? Mycopathologia. 2003;156(4):349-56. doi: 10.1023/b:myco.0000003606.13934.74. PMID: 14682462.

[7] Chattopadhyay P, Upadhyay A, Agnihotri A, Karmakar S, Ghoyary D, Veer V. Comparative hematoxicity of fusirium mycotoxin in experimental sprague-dawley rats. Toxicol Int. 2013;20(1):25-29. doi:10.4103/0971-6580.111552

[8] Scafuri, B., Varriale, A., Facchiano, A. et al. Binding of mycotoxins to proteins involved in neuronal plasticity: a combined in silico/wet investigation. Sci Rep 7, 15156 (2017).

[9] Campbell AW, Thrasher JD, Gray MR, Vojdani A. Mold and mycotoxins: effects on the neurological and immune systems in humans. Adv Appl Microbiol. 2004;55:375-406. doi: 10.1016/S0065-2164(04)55015-3. PMID: 15350803.

[10] McDonnell AM, Dang CH. Basic review of the cytochrome p450 system. J Adv Pract Oncol. 2013;4(4):263-268. doi:10.6004/jadpro.2013.4.4.7

[11] Facciolá G, Hidestrand M, von Bahr C, Tybring G. Cytochrome P450 isoforms involved in melatonin metabolism in human liver microsomes. Eur J Clin Pharmacol. 2001 Mar;56(12):881-8. doi: 10.1007/s002280000245. PMID: 11317475.

[12] Ratnaseelan AM, Tsilioni I, Theoharides TC. Effects of Mycotoxins on Neuropsychiatric Symptoms and Immune Processes. Clin Ther. 2018 Jun;40(6):903-917. doi: 10.1016/j.clinthera.2018.05.004. Epub 2018 Jun 5. PMID: 29880330.

[13] Omar RF, Gelboin HV, Rahimtula AD. Effect of cytochrome P450 induction on the metabolism and toxicity of ochratoxin A. Biochem Pharmacol. 1996 Feb 9;51(3):207-16. doi: 10.1016/0006-2952(95)02194-9. PMID: 8573185.

[14]  Thompson WL, Wannemacher RW Jr. 1990. In vivo effects of T-2 toxin on synthesis of proteins and DNA in rat tissues. Toxicology and Applied Pharmacology 105:482–491

[15] Claeys, L, Romano, C, De Ruyck, K, et al. Mycotoxin exposure and human cancer risk: a systematic review of epidemiological studies. Compr Rev Food Sci Food Saf. 2020; 19: 1449– 1464.

[16] Ghazi T, Nagiah S, Chuturgoon AA. Fusaric acid decreases p53 expression by altering promoter methylation and m6A RNA methylation in human hepatocellular carcinoma (HepG2) cells. Epigenetics. 2021 Jan;16(1):79-91. doi: 10.1080/15592294.2020.1788324. Epub 2020 Jul 7. PMID: 32631113; PMCID: PMC7889137.

[17] Bin-Umer MA, McLaughlin JE, Butterly MS, McCormick S, Tumer NE. Elimination of damaged mitochondria through mitophagy reduces mitochondrial oxidative stress and increases tolerance to trichothecenes. Proc Natl Acad Sci U S A. 2014 Aug 12;111(32):11798-803. doi: 10.1073/pnas.1403145111. Epub 2014 Jul 28. PMID: 25071194; PMCID: PMC4136610.

[18] Bin-Umer MA, McLaughlin JE, Basu D, McCormick S, Tumer NE. Trichothecene mycotoxins inhibit mitochondrial translation–implication for the mechanism of toxicity. Toxins (Basel). 2011;3(12):1484-1501. doi:10.3390/toxins3121484

[19] Bitnun A, Nosal RM. Stachybotrys chartarum (atra) contamination of the indoor environment: Health implications. Paediatr Child Health. 1999;4(2):125-129. doi:10.1093/pch/4.2.125

[20] Islam Z, Harkema JR, Pestka JJ. Satratoxin G from the black mold Stachybotrys chartarum evokes olfactory sensory neuron loss and inflammation in the murine nose and brain. Environ Health Perspect. 2006 Jul;114(7):1099-107. doi: 10.1289/ehp.8854. PMID: 16835065; PMCID: PMC1513335.

[21] Porter AG, Jänicke RU. Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 1999 Feb;6(2):99-104. doi: 10.1038/sj.cdd.4400476. PMID: 10200555.

[22] Kankkunen P, Rintahaka J, Aalto A, Leino M, Majuri ML, Alenius H, Wolff H, Matikainen S. Trichothecene mycotoxins activate inflammatory response in human macrophages. J Immunol. 2009 May 15;182(10):6418-25. doi: 10.4049/jimmunol.0803309. PMID: 19414795.

[23] Kralova, J., Dvorak, M., Koc, M. et al. p38 MAPK plays an essential role in apoptosis induced by photoactivation of a novel ethylene glycol porphyrin derivative. Oncogene 27, 3010–3020 (2008).

[24] Agrawal, M., Bhaskar, A. S. B., & Rao, P. L. (2015). Involvement of mitogen-activated protein kinase pathway in T-2 toxin-induced cell cycle alteration and apoptosis in human neuroblastoma cells.

[25] Cagnol S, Chambard JC. ERK and cell death: mechanisms of ERK-induced cell death–apoptosis, autophagy and senescence. FEBS J. 2010 Jan;277(1):2-21. doi: 10.1111/j.1742-4658.2009.07366.x. 

[26] Yang GH, Jarvis BB, Chung YJ, Pestka JJ. Apoptosis induction by the satratoxins and other trichothecene mycotoxins: relationship to ERK, p38 MAPK, and SAPK/JNK activation. Toxicol Appl Pharmacol. 2000 Apr 15;164(2):149-60. doi: 10.1006/taap.1999.8888. PMID: 10764628.

[27] Karppanen, E., Rizzo, A., Saari, L. et al. Investigation on Trichothecene-Stimulated Lipid Peroxidation and Toxic Effects of Trichothecenes in Animals. Acta Vet Scand 30, 391–399 (1989).

[28] Yang H, Zhou M, Li H, et al. Effects of Low-level Lipid Peroxidation on the Permeability of Nitroaromatic Molecules across a Membrane: A Computational Study. ACS Omega. 2020;5(10):4798-4806. Published 2020 Mar 6. doi:10.1021/acsomega.9b03462

[29] Su C.; Merlitz H.; Thalmann F.; Marques C.; Sommer J. Coarse-Grained Model of Oxidized Membranes and their Interactions with Nanoparticles of Various Degrees of Hydrophobicity. J. Phys. Chem. C. 2019, 123, 6839–6848. 10.1021/acs.jpcc.8b11909. 

[30] Davis B.; Koster G.; Douet L. J.; Scigelova M.; Woffendin G.; Ward J. M.; Smith A.; Julia Humphries K. G. B. C.; et al. Electrospray Ionization Mass Spectrometry Identifies Substrates and Products of Lipoprotein-Associated Phospholipase a2 in Oxidized Human Low Density Lipoprotein. J. Biol. Chem. 2008, 283, 6428–6437. 10.1074/jbc.M709970200.

[31] Pilon M. Revisiting the membrane-centric view of diabetes. Lipids Health Dis. 2016;15(1):167. Published 2016 Sep 27. doi:10.1186/s12944-016-0342-0

[32] Gallagher PG. Red cell membrane disorders. Hematology Am Soc Hematol Educ Program. 2005:13-8. doi: 10.1182/asheducation-2005.1.13. PMID: 16304353.

[33] Witte ME, Schumacher AM, Mahler CF, Bewersdorf JP, Lehmitz J, Scheiter A, Sánchez P, Williams PR, Griesbeck O, Naumann R, Misgeld T, Kerschensteiner M. Calcium Influx through Plasma-Membrane Nanoruptures Drives Axon Degeneration in a Model of Multiple Sclerosis. Neuron. 2019 Feb 20;101(4):615-624.e5. doi: 10.1016/j.neuron.2018.12.023. Epub 2019 Jan 24. PMID: 30686733; PMCID: PMC6389591.

[34] Cooper ST, Head SI. Membrane Injury and Repair in the Muscular Dystrophies. Neuroscientist. 2015 Dec;21(6):653-68. doi: 10.1177/1073858414558336. Epub 2014 Nov 18. PMID: 25406223.

[35] Pravda J. Crohn’s disease: evidence for involvement of unregulated transcytosis in disease etio-pathogenesis. World J Gastroenterol. 2011;17(11):1416-1426. doi:10.3748/wjg.v17.i11.1416

[36] Yin G, Wang Y, Cen XM, Yang M, Liang Y, Xie QB. Lipid peroxidation-mediated inflammation promotes cell apoptosis through activation of NF-κB pathway in rheumatoid arthritis synovial cells. Mediators Inflamm. 2015;2015:460310. doi:10.1155/2015/460310

[37] Ueno Y. Toxicological features of T-2 toxin and related trichothecenes. Fundam Appl Toxicol. 1984;4(2 Pt 2):S124–S132

[38]  Pestka JJ. Mechanisms of deoxynivalenol-induced gene expression and apoptosis. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2008;25(9):1128-1140. doi:10.1080/02652030802056626

[39] Santini SJ, Cordone V, Falone S, et al. Role of Mitochondria in the Oxidative Stress Induced by Electromagnetic Fields: Focus on Reproductive Systems [published correction appears in Oxid Med Cell Longev. 2020 May 17;2020:5203105]. Oxid Med Cell Longev. 2018;2018:5076271. Published 2018 Nov 8. doi:10.1155/2018/5076271

[40] Nadtochiy SM, Tompkins AJ, Brookes PS. Different mechanisms of mitochondrial proton leak in ischaemia/reperfusion injury and preconditioning: implications for pathology and cardioprotection. Biochem J. 2006 May 1;395(3):611-8. doi: 10.1042/BJ20051927. PMID: 16436046; PMCID: PMC1462692.

[41] Pall ML. Electromagnetic fields act via activation of voltage-gated calcium channels to produce beneficial or adverse effects. J Cell Mol Med. 2013 Aug;17(8):958-65. doi: 10.1111/jcmm.12088. Epub 2013 Jun 26. PMID: 23802593; PMCID: PMC3780531.

[42] Marchionni I, Paffi A, Pellegrino M, Liberti M, Apollonio F, Abeti R, Fontana F, D’Inzeo G, Mazzanti M. Comparison between low-level 50 Hz and 900 MHz electromagnetic stimulation on single channel ionic currents and on firing frequency in dorsal root ganglion isolated neurons. Biochim Biophys Acta. 2006 May;1758(5):597-605. doi: 10.1016/j.bbamem.2006.03.014. Epub 2006 Apr 5. PMID: 16713990.

[43] Catterall WA. Voltage-gated calcium channels. Cold Spring Harb Perspect Biol. 2011;3(8):a003947. Published 2011 Aug 1. doi:10.1101/cshperspect.a003947

[44] MITCHELL, P. Coupling of Phosphorylation to Electron and Hydrogen Transfer by a Chemi-Osmotic type of Mechanism. Nature 191, 144–148 (1961).

[45] Cadenas, S. (2018). Mitochondrial uncoupling, ROS generation and cardioprotection. Biochimica et Biophysica Acta (BBA) – Bioenergetics, 1859(9), 940–950. doi:10.1016/j.bbabio.2018.05.019

[46] Bortner CD, Gomez-Angelats M, Cidlowski JA. Plasma membrane depolarization without repolarization is an early molecular event in anti-Fas-induced apoptosis. J Biol Chem. 2001 Feb 9;276(6):4304-14. doi: 10.1074/jbc.M005171200. Epub 2000 Oct 24. PMID: 11050080.

[47] Kahya MC, Nazıroğlu M, Çiğ B. Selenium reduces mobile phone (900 MHz)-induced oxidative stress, mitochondrial function, and apoptosis in breast cancer cells. Biol Trace Elem Res. 2014 Aug;160(2):285-93. doi: 10.1007/s12011-014-0032-6. Epub 2014 Jun 27. PMID: 24965080.

[48] Pandey N, Giri S, Das S, Upadhaya P. Radiofrequency radiation (900 MHz)-induced DNA damage and cell cycle arrest in testicular germ cells in swiss albino mice. Toxicol Ind Health. 2017 Apr;33(4):373-384. doi: 10.1177/0748233716671206. Epub 2016 Oct 14. PMID: 27738269.

[49] C. Polk, E. Postow (Eds.), Handbook of Biological Effects of Electromagnetic Fields, CRC Press, Boca Raton (1986)

[50] Wang H, Zhang X. Magnetic Fields and Reactive Oxygen Species. Int J Mol Sci. 2017;18(10):2175. Published 2017 Oct 18. doi:10.3390/ijms18102175

[51] Wong-Ekkabut J, Xu Z, Triampo W, Tang IM, Tieleman DP, Monticelli L. Effect of lipid peroxidation on the properties of lipid bilayers: a molecular dynamics study. Biophys J. 2007;93(12):4225-4236. doi:10.1529/biophysj.107.112565

[52] Stark G. Functional consequences of oxidative membrane damage. J Membr Biol. 2005 May;205(1):1-16. doi: 10.1007/s00232-005-0753-8. PMID: 16245038.

[53] Gooley JJ, Chamberlain K, Smith KA, et al. Exposure to room light before bedtime suppresses melatonin onset and shortens melatonin duration in humans. J Clin Endocrinol Metab. 2011;96(3):E463-E472. doi:10.1210/jc.2010-2098

[54] Burch JB, Reif JS, Yost MG. Geomagnetic disturbances are associated with reduced nocturnal excretion of a melatonin metabolite in humans. Neurosci Lett. 1999 May 14;266(3):209-12. doi: 10.1016/s0304-3940(99)00308-0. PMID: 10465710.

[55] Milad Iranshahy, Leila Etemad, Abolfazl Shakeri, et al. Protective activity of melatonin against mycotoxins-induced toxicity: a reviewToxicological & Environmental Chemistry Volume 101, 2019 – Issue 9-10  DOI: 10.1080/02772248.2020.1731751

[56] Xu Y, Zhang KH, Sun MH, et al. Protective Effects of Melatonin Against Zearalenone Toxicity on Porcine Embryos in vitro. Front Pharmacol. 2019;10:327. Published 2019 Apr 5. doi:10.3389/fphar.2019.00327

[57] Okutan H, Aydin G, Ozcelik N. Protective role of melatonin in ochratoxin a toxicity in rat heart and lung. J Appl Toxicol. 2004 Nov-Dec;24(6):505-12. doi: 10.1002/jat.1010. PMID: 15558833.

[58] Gamal H. El-Sokkary, Russel J. Reiter, Dun-Xian Tan, Seok Joong Kim, Javier Cabrera, INHIBITORY EFFECT OF MELATONIN ON PRODUCTS OF LIPID PEROXIDATION RESULTING FROM CHRONIC ETHANOL ADMINISTRATION, Alcohol and Alcoholism, Volume 34, Issue 6, November 1999, Pages 842–850,

[59] Yoon YM, Kim HJ, Lee JH, Lee SH. Melatonin Enhances Mitophagy by Upregulating Expression of Heat Shock 70 kDa Protein 1L in Human Mesenchymal Stem Cells under Oxidative Stress. Int J Mol Sci. 2019;20(18):4545. Published 2019 Sep 13. doi:10.3390/ijms20184545

[60] Ma Y, Zhao Q, Shao Y, Cao MZ, Zhao M, Wang D. Melatonin inhibits the inflammation and apoptosis in rats with diabetic retinopathy via MAPK pathway. Eur Rev Med Pharmacol Sci. 2019 Aug;23(3 Suppl):1-8. doi: 10.26355/eurrev_201908_18620. Retraction in: Eur Rev Med Pharmacol Sci. 2020 Jul;24(14):7545. PMID: 31389568

[61] Luchetti F, Betti M, Canonico B, Arcangeletti M, Ferri P, Galli F, Papa S. ERK MAPK activation mediates the antiapoptotic signaling of melatonin in UVB-stressed U937 cells. Free Radic Biol Med. 2009 Feb 1;46(3):339-51. doi: 10.1016/j.freeradbiomed.2008.09.017. Epub 2008 Sep 27. PMID: 18930812.

[62] Santoro, R., Marani, M., Blandino, G. et al. Melatonin triggers p53Ser phosphorylation and prevents DNA damage accumulation. Oncogene 31, 2931–2942 (2012).

[63] Nikhil Maroli Melatonin Protects T-2 toxin-induced neuronal stress through Acetylcholinesterase & Cytochrome P450 receptor-mediated signaling bioRxiv preprint doi:

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