Immunomodulatory effects of l-carnitine and q10 in mouse spleen exposed to low-frequency high-intensity magnetic field
Introduction
With the increased urbanisation and the fact that electrical appliances are commonly used in our daily life, human beings and many other living organisms as well, are inevitably subject to the frequent exposure to low-frequency electromagnetic fields (EMFs) (Li and Chow, 2001). EMFs range from cosmic rays to the static magnetic fields of earth. Between these extremes is visible light, separating the whole range into ionising and non-ionising radiations (Jahn, 2000). Extremely low EMFs, to which belongs the frequency used in the current study, lie in the range of 3–3000 Hz (Repacholi and Greenbaum, 1999). Alternating current has a frequency of 60 Hz in the USA and Canada, whereas it reaches 50 Hz in other countries. Magnetic field intensity is measured in international units called Tesla (T) or in the American units called Gauss (G). One unit Tesla equals 104 Gauss (Repacholi and Greenbaum, 1999).
Biological effects of low-frequency fields have been studied during the last three decades. Unfortunately, results of epidemiological studies in this research area have been contentious; results indicated that there is a link between the prevalence of adverse biologic effects and low-frequency field's exposure, but there is not a significant association between insult and exposure (Anonymous, 1999, Orbach-Arbouys et al., 1999, Caplan et al., 2000). Both low- and high-intensity low-frequency fields were subject to extensive investigations in an attempt to settle risk-assessment guidelines for the human exposure.
Though residential exposure to low-frequency EMFs such as those from high-voltage powerlines results in low-intensity fields, possibility of human exposure to high-intensity fields has been increased lately due to the increased extent of modernisation. Actually, some electric devices such as the magnetic resonance image (Schenck, 2000) could induce fields that may reach more than 1000-fold the intensity of the residential levels of EMFs. Further, human beings could be exposed to high-intensity magnetic fields that may reach thousands Gauss from some magnetic belts and magnetic pads, as well as steel-belted radial tires (Milham et al., 1999).
An array of experimental studies have been conducted in different species to evaluate the effects of low-frequency (50–60 Hz) waves with different field intensities (0.1–1000 μT) on immune system. The available literature on immune function has both strengths and weaknesses. Most of the studies conducted to date have investigated a wide variety of immune function endpoints, including immune system structures, cell- and humoural-mediated immunity, and innate immunity (Mevissen, 1999). These studies have been conducted in diverse species including mice, rats, baboons, sheep and humans. However, data so far obtained revealed debatable conclusions.
Tenforde and Shifrine (1984) have demonstrated that following a 6-week exposure of LAF1/J mice to a 1.5 Tesla stationary magnetic field no significant differences were observed in the responses of spleen lymphocytes between exposed and control groups. Also, Ramoni et al. (1995) have reported that 50-Hz Sinusoidal magnetic fields with flux intensities up to 10 mT do not affect the cytotoxic activity of human natural killer (NK) cells. Further, no effects of linearly polarised 60-Hz magnetic fields up to 10 G intensity were found on the host immune response in mice (House et al., 1996).
Contrariwise, a 6-week exposure to 50 μT (0.5 G) field resulted in reductions of surface marker antigens, interlukin 2 receptor expression, and proliferative response to Pokweed mitogen in blood lymphocytes derived from baboons (Murthy et al., 1995). Tremblay et al. (1996) have also documented that in vivo exposure of Fisher rats for 6 weeks to 60-Hz magnetic field with intensity up to 2000 μT induced significant immunological perturbations on effector cells of both natural and adaptive immunity in a dose-dependent manner. Besides, Mevissen et al. (1998) have reported that exposure of female Sprague–Dawley rats to 50-Hz, 100 μT magnetic field for 13 weeks induced complex effects on the mitogenic responsiveness of T cells, which may lead to impaired immune surveillance after long-term exposure.
l-Carnitine is a naturally occurring quaternary ammonium compound, which is endogenously synthesised in man and also found in the diet (Goa and Brogden, 1987). It is an essential cofactor of several enzymes necessary for the transformation of long-chain fatty acids, and also acts as a scavenger of oxygen free radicals in mammalian tissues (Izgut-Uysal et al., 2001). l-carnitine has proven efficacy in ischemic heart probably by selectively reducing the accumulation of mitochondrial long-chain acyl-CoA, as well as long-chain acylcarnitine (Fujisawa et al., 1992). The observation that leukocytes, including peripheral blood mononuclear cells (PBMNs), are enriched in carnitines (Deufel, 1990) first suggested that l-carnitine and its congeners might regulate the immune networks. Previous reports have demonstrated the enhancement of immune responses by l-carnitine supplementation (De Simone et al., 1982a, De Simone et al., 1985, Monti et al., 1989). In addition, l-carnitine has been shown to protect cells against toxicity of reactive oxygen intermediates (Monti et al., 1992). Famularo et al. (1994) have demonstrated anti-apoptotic effects of l-carnitine and its congeners in vitro. A reduced pool of carnitines has been found in either serum or tissues, or both, in disorders with unregulated immune responses such as the chronic fatigue syndrome (Majeed et al., 1995) and septic shock (Famularo et al., 1995), as well as AIDS patients (Famularo and De Simone, 1995). This further lends support to the view that a normal endogenous pool of carnitines is crucial to the maintenance of normal immune system.
Coenzyme Q (Q10) is well defined as a crucial component of the oxidative phosphorylation process in mitochondria which converts the energy in carbohydrates and fatty acids into ATP to drive cellular machinery and synthesis. Q10 can undergo oxidation/reduction reactions in other cell membranes such as lysosomes, Golgi apparatus and plasma membranes. It has been shown that Q10 could have a function in redox control of cell signalling and gene expression as evidenced from its role in cell growth stimulation, inhibition of apoptosis, control of thiol groups, formation of hydrogen peroxide and control of membrane channels (Crane, 2001). Q10 was found to completely suppress the elevation in lipid peroxide level induced by LPS in mouse liver (Suzuki, 1991). Being non-specific stimulant of the immune host defence system (Bliznakov, 1978), Q10 has been observed to protect against tumour growth and to enhance viral immunity in experimental animals, as well as it elicited remarkable improvement in AIDS patients (Tanner, 1992).
The current study was conducted to investigate the biological effects of low-frequency (50 Hz) high-intensity (20 mT; 200 G) electromagnetic field on some immune parameters in mice. Though this intensity is more than 10-fold the residential exposure levels from high-voltage powerlines, it is about 1/10–1/25 times the magnetic fields from some magnetic belts and magnetic pads, as well as magnetic resonance instruments. Possible protection by two non-specific immunostimulants to the host defence, namely l-carnitine and Q10, was also assessed. Parameters undertaken in the present work were: total body weight and relative spleen/body weight ratio, total and differential counts of white blood cells (WBCs), viability of splenocytes, as well as lymphoproliferation assays using lectins-induced 3[H]thymidine incorporation into splenocytes as a measure of DNA synthesis and consequently a measure of lymphocyte proliferation.
Section snippets
Animals
Male healthy Swiss albino mice weighing 20–25 g were obtained from the National Centre for Radiation Research and Technology (NCRRT), Cairo, Egypt. The animals were housed in the animal facility of the Pharmacy College, Al-Azhar University, Cairo, Egypt, at 23±1 °C and 55% humidity with 12-h light:12-h dark cycle. The mice were fed a standard pellet diet (El-Nasr Co., Abou-Zaabal, Cairo, Egypt), and water ad libitum. The animal experiments have been approved by the Committee of Animal
Results
The effects of magnetic field alone and in combination with l-carnitine or Q10 on the immune parameters tested in mouse blood and spleen are compiled in Table 1.
Neither l-carnitine nor Q10 had any effects on the immune parameters measured in normal mice.
Magnetic field significantly decreased the animal body weight by 7% compared with control animals, but it had no effect on spleen relative weight. Pre-treatment with either l-carnitine or with Q10 did not add to the effect of magnetic field on
Discussion
One of the most contentious issues in the scientific community today is that of the biological effects of EMFs, and whether or not they are adversely affecting our health. For decades, researchers have been concerning about the bioeffects of low-frequency, low-intensity EMFs, which are comparable to both residential and occupational exposure levels in many work fields. Due to extensive modernisation and sophistication of our daily life, high intensity fields from some EMF-producing instruments
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