Unexposed Rats Research Articles

Exposure to 900 MHz electromagnetic fields activates the mkp-1/ERK pathway and causes blood-brain barrier damage and cognitive impairment in rats

With the rapid increase in the number of mobile phone users, the potential adverse effects of the electromagnetic field radiation emitted by a mobile phone has become a serious concern. This study demonstrated, for the first time, the blood-brain barrier and cognitive changes in rats exposed to 900MHz electromagnetic field (EMF) and aims to elucidate the potential molecular pathway underlying these changes. A total of 108 male Sprague-Dawley rats were exposed to a 900MHz, 1mW/cm2 EMF or sham (unexposed) for 14 or 28 days (3h per day). The specific energy absorption rate (SAR) varied between 0.016 (whole body) and 2W/kg (locally in the head). In addition, the Morris water maze test was used to examine spatial memory performance determination. Morphological changes were investigated by examining ultrastructural changes in the hippocampus and cortex, and the Evans Blue assay was used to assess blood brain barrier (BBB) damage. Immunostaining was performed to identify heme oxygenase-1 (HO-1)-positive neurons and albumin extravasation detection. Western blot was used to determine HO-1 expression, phosphorylated ERK expression and the upstream mediator, mkp-1 expression. We found that the frequency of crossing platforms and the percentage of time spent in the target quadrant were lower in rats exposed to EMF for 28 days than in rats exposed to EMF for 14 days and unexposed rats. Moreover, 28 days of EMF exposure induced cellular edema and neuronal cell organelle degeneration in the rat. In addition, damaged BBB permeability, which resulted in albumin and HO-1 extravasation were observed in the hippocampus and cortex. Thus, for the first time, we found that EMF exposure for 28 days induced the expression of mkp-1, resulting in ERK dephosphorylation. Taken together, these results demonstrated that exposure to 900MHz EMF radiation for 28 days can significantly impair spatial memory and damage BBB permeability in rat by activating the mkp-1/ERK pathway.

Evaluation of offspring sex ratio, sex hormones and antioxidant enzymes following exposure to methyl tertiary butyl ether in adult male Sprague-Dawley rats.

Methyl tertiary butyl ether (MTBE) is an oxygenated fuel additive which has been used widely in many parts of the world. This experiment was performed to determine the effect of MTBE on offspring sex ratio, sex hormones and antioxidant enzymes. A total of 20 adult Sprague-Dawley male rats were divided into four groups and received 0, 400, 800 and 1600 mg/kg/day MTBE by gavages for 30 consecutive days. At the end of the experiment, blood samples were taken for determination of sex hormones and antioxidant enzymes. Then, male rats were mated with healthy unexposed female rats and sex of offspring was determined after birth. Sex ratio was 0.48, 0.50, 0.43 and 0.50 in 0, 400, 800 and 1600 mg/kg/day MTBE groups, respectively (P = 0.91). There was significant decreasing trend for luteinizing hormone (LH) and testosterone in experimental groups (rs = -0.50, P = 0.030 and rs = -0.67, P = 0.002, respectively). No changes were observed for superoxide dismutase. However, decrease in glutathione peroxidase (GPX) was observed in all treatment groups compared with control which was significant in 400 mg/kg/day MTBE group (P = 0.016). The present study showed that paternal exposure to oral MTBE has no effect on offspring sex ratio; while, MTBE exposure could exert dose-dependent changes in serum testosterone and LH in treatment groups. The results of the present study, need to be clarified in the future studies.

Hypobaric Hypoxia Imbalances Mitochondrial Dynamics in Rat Brain Hippocampus.

Brain is predominantly susceptible to oxidative stress and mitochondrial dysfunction during hypobaric hypoxia, and therefore undergoes neurodegeneration due to energy crisis. Evidences illustrate a high degree of association for mitochondrial fusion/fission imbalance and mitochondrial dysfunction. Mitochondrial fusion/fission is a recently reported dynamic mechanism which frequently occurs among cellular mitochondrial network. Hence, the study investigated the temporal alteration and involvement of abnormal mitochondrial dynamics (fusion/fission) along with disturbed mitochondrial functionality during chronic exposure to hypobaric hypoxia (HH). The Sprague-Dawley rats were exposed to simulated high altitude equivalent to 25000 ft for 3, 7, 14, 21, and 28 days. Mitochondrial morphology, distribution within neurons, enzyme activity of respiratory complexes, Δψ m, ADP: ATP, and expression of fission/fusion key proteins were determined. Results demonstrated HH induced alteration in mitochondrial morphology by damaged, small mitochondria observed in neurons with disturbance of mitochondrial functionality and reduced mitochondrial density in neuronal processes manifested by excessive mitochondrial fragmentation (fission) and decreased mitochondrial fusion as compared to unexposed rat brain hippocampus. The study suggested that imbalance in mitochondrial dynamics is one of the noteworthy mechanisms occurring in hippocampal neurons during HH insult.

Chronic intermittent hypoxia and hypercapnia inhibit the hypothalamic paraventricular nucleus neurotransmission to parasympathetic cardiac neurons in the brain stem.

Obstructive sleep apnea is associated with chronic intermittent hypoxia/hypercapnia (CIHH) episodes during sleep that heighten sympathetic and diminish parasympathetic activity to the heart. Although one population of neurons in the paraventricular nucleus of the hypothalamus strongly influences sympathetic tone and has increased activity after CIHH, little is known about the role of this pathway to parasympathetic neurons and how this network is altered in CIHH. We hypothesized that CIHH inhibits the excitatory pathway from the paraventricular nucleus of the hypothalamus to parasympathetic cardiac vagal neurons in the brain stem. To test this hypothesis, channelrhodopsin was selectively expressed, using viral vectors, in neurons in the paraventricular nucleus of the hypothalamus and channelrhodopsin-expressing fibers were photoactivated to evoke postsynaptic currents in cardiac vagal neurons in brain stem slices. Excitatory postsynaptic currents were diminished in animals exposed to CIHH. The paired-pulse and prolonged facilitation of the postsynaptic current amplitudes and frequencies evoked by paired and bursts of photoactivation of channelrhodopsin fibers, respectively, occurred in unexposed rats but were blunted in CIHH animals. In response to an acute challenge of hypoxia/hypercapnia, the amplitude of postsynaptic events was unchanged during, but increased after hypoxia/hypercapnia in unexposed animals. In contrast, postsynaptic currents were inhibited during hypoxia/hypercapnia in rats exposed to CIHH. In conclusion, the excitatory pathway to cardiac vagal neurons is diminished in response to both acute and chronic exposures to hypoxia/hypercapnia. This could elicit a reduced cardioprotective parasympathetic activity and an enhanced risk of adverse cardiovascular events in episodes of apnea and chronic obstructive sleep apnea.

Effect of cement dust on reproductive performance and some physiological parameters in albino rats

A total of 30 Albino rats of 12 weeks of age were sourced from Altran Farm in Nsukka and acclimatized for 3 weeks. Five males and five females were exposed to cement dust for 3 months at the Eastern Blocks and Concrete Industries Limited, Nsukka, Nigeria. Ten males and ten females were kept in an environment free from cement dust but within the same climatic zone and were the unexposed. The effect of cement dust was then determined on reproductive performance and some physiological parameters of the rats. The uterus of the exposed females showed significant decrease (p < 0.05) in weight (2.19 ± 0.05) when compared to that of the unexposed females (4.09 ± 0.55). The mean epididymal sperm reserve of the exposed males (12.25 ± 2.17) was significantly reduced (p < 0.05) when compared to that of the control group (18.46 ± 0.325). The mean testicular weight of the exposed males (1.03 ± 0.09) was significantly reduced when compared to the control (1.42 ± 0.026). The mean fetal weight and crown rump length of the offsprings from the exposed females (4.07 ± 0.17, 3.12 ± 0.09, respectively) were significantly reduced (p < 0.05) when compared to those of the offsprings from the unexposed females (5.64 ± 0.10, 5.36 ± 0.17, respectively). The mean number of offsprings from exposed males (6.00 ± 0.45) was significantly reduced (p < 0.05) when compared to that from unexposed males (9.80 ± 0.37). The hematological evaluation showed significant reductions (p < 0.05) in mean PCV, HB, RBC, and WBC of the exposed rats (27.50 ± 2.20, 8.31 ± 0.61, 3.61 ± 0.82, 4.70 ± 0.63, respectively) when compared to the unexposed (43.17 ± 3.52, 14.1 ± 0.72, 7.21 ± 0.45, 8.48 ± 0.86, respectively). The results of serum enzyme levels (AST, ALP, and ALT) of the exposed rats (87.12 ± 3.42, 93.87 ± 14.18, 45.06 ± 5.25, respectively) were significantly increased (p < 0.05) when compared to the unexposed rats (56.98 ± 8.38, 24.71 ± 2.11, 25.72 ± 2.96, respectively).

Exposure to gasoline power generator exhaust fume negatively affected hematological, liver and kidney function parameters in female albino rats (766.7)

The lack of constant electricity power supply to meet utility usage in developing countries like Nigeria has warrant the use of petroleum powered generators to supply electricity. There has also been dearth research on the effects of exposure to fumes from the generators thus necessitating the need for this research. This study therefore investigated hematological, liver, kidney, hormonal and histopathological changes in female albino rats exposed to gasoline power generator exhaust fume at varied distance of 100, 200 and 300 meter respectively after 42 days. Present study showed that there was significant (p &lt; 0.05) increase in packed cell volume, white blood cells, lymphocytes, neutrophiles, monocytes and platelets in the exposed animals compared to control unexposed rats. Liver and kidney function parameters were also significantly (p &lt; 0.05) increased whereas there were no significant (p &lt;0.05) difference in follicle stimulating hormone, prolactin, progesterone and estradiol amongst the animals, however, luteinizing hormone was increased in 300 meter exposed rats. Histopathological investigation showed degenerated organs in the exposed animals compared to control. Generally, the observed variations in the parameters were proportional to the distance from source of exposure. This study demonstrated that constant exposure to gasoline power generator as is the case in Nigeria could induce some biochemical changes which may be toxic to exposed individuals and may lead to adverse health conditions such as cancer.

Developmental Effects of Neonatal Isoflurane and Sevoflurane Exposure in Rats

The general anesthetics, isoflurane and sevoflurane, cause developmental abnormalities in neonatal animal models via incompletely understood mechanisms. Despite many common molecular targets, isoflurane and sevoflurane exhibit substantial differences in their actions. The authors sought to determine whether these differences can also be detected at the level of neurodevelopmental effects. Postnatal rats, 4-6 days old, were exposed to 1.2% isoflurane or 2.1% sevoflurane for 1-6 h and studied for immediate and delayed effects. Isoflurane exposure was associated with weaker seizure-like electroencephalogram patterns than sevoflurane exposure. Confronted with a new environment at a juvenile age, the sevoflurane-exposed rats spent significantly more time in an "immobile" state than unexposed rats. Electroencephalographic (mean ± SE, 55.5 ± 12.80 s vs. 14.86 ± 7.03 s; P = 0.014; n = 6-7) and spontaneous behavior (F(2,39) = 4.43; P = 0.018) effects of sevoflurane were significantly diminished by pretreatment with the Na-K-2Cl cotransporter inhibitor bumetanide, whereas those of isoflurane were not. Pretreatment with bumetanide, however, diminished isoflurane-induced activation of caspase-3 in the cerebral cortex (F(2,8) = 22.869; P = 0.002) and prevented impairment in sensorimotor gating function (F(2,36) = 5.978; P = 0.006). These findings in combination with results previously reported by the authors suggest that isoflurane and sevoflurane produce developmental effects acting via similar mechanisms that involve an anesthetic-induced increase in neuronal activity. At the same time, differences in their effects suggest differences in the mediating mechanisms and in their relative safety profile for neonatal anesthesia.

Potential Changes in Rat Spermatogenesis and Sperm Parameters after Inhalation of Boswellia papyrifera and Boswellia carterii Incense

In this study the effect of Boswellia papyrifera (B. papyrifera) and Boswellia carterii (B. carterii) smoke exposure on spermatogenesis and sperm parameters in male albino rats was investigated. Rats (n = 11) were exposed daily in smoking chambers to smoke emanated by burning 4 g each of either B. papyrifera or B. carterii for 48 days. At the end of exposure duration rats were killed, and the testes were excised and analysed for histopathological and ultrastructural changes. Sperm analysis including total sperm count, motility, velocity and relative percentage of abnormal sperms were recorded. Rats exposed to B. papyrifera and B. carterii showed significant disturbances in spermatogenetic patterns and changes in sperm kinetics compared to unexposed rats. Atrophied seminiferous tubules with dynamic changes were also noticed. The boundaries of intercellular and intracellular vacuoles were seen in the Sertoli cells. Furthermore, in spermatids acrosomal vesicles were not fully formed. Degenerating spermatids were devoid of their nuclear membrane with electron dense matrix and vacuolization. Structural changes in Leydig cells were observed. Sperm analysis in exposed rats exhibited significant decrease in the sperm count, motility, speed and an increase in sperm anomalies when compare to controls. These findings demonstrate that the B. papyrifera and B. carterii smoke affects the process of spermatogenesis and sperm parameters and indicate the detrimental effects of these incense materials on human reproductive system.

Waterborne manganese exposure alters plasma, brain, and liver metabolites accompanied by changes in stereotypic behaviors

Overexposure to waterborne manganese (Mn) is linked with cognitive impairment in children and neurochemical abnormalities in other experimental models. In order to characterize the threshold between Mn-exposure and altered neurochemistry, it is important to identify biomarkers that positively correspond with brain Mn-accumulation. The objective of this study was to identify Mn-induced alterations in plasma, liver, and brain metabolites using liquid/gas chromatography–time of flight–mass spectrometry metabolomic analyses; and to monitor corresponding Mn-induced behavior changes. Weanling Sprague–Dawley rats had access to deionized drinking water either Mn-free or containing 1g Mn/L for 6weeks. Behaviors were monitored during the sixth week for a continuous 24h period while in a home cage environment using video surveillance. Mn-exposure significantly increased liver, plasma, and brain Mn concentrations compared to control, specifically targeting the globus pallidus (GP). Mn significantly altered 98 metabolites in the brain, liver, and plasma; notably shifting cholesterol and fatty acid metabolism in the brain (increased oleic and palmitic acid; 12.57 and 15.48 fold change (FC), respectively), and liver (increased oleic acid, 14.51 FC; decreased hydroxybutyric acid, −14.29 FC). Additionally, Mn-altered plasma metabolites homogentisic acid, chenodeoxycholic acid, and aspartic acid correlated significantly with GP and striatal Mn. Total distance traveled was significantly increased and positively correlated with Mn-exposure, while nocturnal stereotypic and exploratory behaviors were reduced with Mn-exposure and performed largely during the light cycle compared to unexposed rats. These data provide putative biomarkers for Mn-neurotoxicity and suggest that Mn disrupts the circadian cycle in rats.

Oxidative and Antioxidative Effects of Desflurane and Sevoflurane on Rat Tissue in Vivo

General anaesthetics are often used in patients who are under oxidative stress due to a critical illness or surgical trauma. Some anaesthetics may worsen oxidative stress and some may act as antioxidants. The aim of this study was to evaluate liver, brain, kidney, and lung tissue oxidative stress in rats exposed to desflurane and sevoflurane and in unexposed rats. The animals were divided in three groups: control (received only air); sevoflurane (8 %), and desflurane (4 %). After four hours of exposure, we evaluated the levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), Cu, and Zn. Exposure to either of the anaesthetics significantly increased lung MDA levels compared to control (Mann-Whitney U test; P<0.05), probably because it is the tissue directly exposed to anaesthetic gases. Oxidative stress and antioxidant activity in other tissues varied between the desflurane and sevoflurane groups. Our results suggest that anaesthesiologist should not only be aware of the oxidative or antioxidative potential of anaesthetics they use, but should also base their choices on organs which are the most affected by their oxidative action.

Efeito da exposição à fumaça de cigarro durante a prenhez e a lactação de ratas e sua prole sobre parâmetros séricos e morfométricos

to investigate the effect of cigarette smoke exposure on body and tissue weight gain, serum parameters and milk yield during pregnancy and lactation in rats, and the impact on offspring from birth toil young adulthood. 40 Wistar pregnant rats were randomly divided into: CG - not exposed to cigarette smoke and sacrificed at the end of pregnancy; CL - not exposed to cigarette smoke and sacrificed at the end of lactation; FG - exposed to cigarette smoke and sacrificed at the end of pregnancy; FL - exposed to cigarette smoke and sacrificed at the end of lactation. The offspring were separated by gender and divided according to their mothers' groups. Tissue weight, body weight and serum parameters were evaluated in rats and offspring. Milk yield per pup was calculated. body weight was decreased in FL during lactation (CL=267.0 ± 7.2; FL=235.5 ± 7.2 g*,*p<0.05). Adipose tissue was not detected in the CL and FL groups, and was reduced in FG compared to CG (CG=3.3 ± 0.3; FG=2.4 ± 0.3 g*, *p<0.05). Rats exposed to cigarette smoke had higher blood glucose levels (CG=113 ± 17, CL=86 ± 16, FG=177 ± 21*, FL=178 ± 23 mg/dL*, *p<0.05 CG versus FG e CL versus FL), CL and FL groups presented lower HDL-cholesterol with no change in total cholesterol. Finally, rats exposed to cigarette smoke had lower milk yield compared to unexposed rats (CL=6.7 ± 0.4, FL=5.4 ± 0.3 g*, *p<0.05). In offspring from the FG and FL groups, there was a decrease of body weight from birth to young adulthood, with no changes in gastrocnemius, liver or heart weights in any group, and adipose tissue was no detected in female offspring. There was an increase in blood glucose in offspring of both sexes from rats exposed to cigarette smoke (males: Pcg=107 ± 10.5, Pcl=115 ± 8.6, Pfg=148 ± 16.8*, Pfl=172 ± 11.2**; females: Pcg=109 ± 27.2, Pcl=104 ± 9.7, Pfg=134 ± 20.0*, Pfl=126 ± 13.3**; p<0.05 *Pcg versus Pfg and **Pcl versus Pfl). exposure to cigarette smoke provokes impairment of morphometric and serum parameters during pregnancy and lactation both in mothers and offspring, which is maintained during young adulthood.

Response to Comments of Peter G. Mantle

The apparently high yield of testis tumors (25%) in rats exposed long-term to Ochratoxin A (OTA) is uninterpretable without data on tumor yield in unexposed rats. Conversely, our demonstration that prenatal exposure to OTA induces DNA adducts in the testes of newborn mice and the absence of these adducts in the testes of mice not exposed prenatally to OTA, is evidence for the presumptive carcinogenicity of OTA in the testis. Together with recent data showing that prenatal exposure to OTA depresses expression of DMRT1, a tumor suppressor gene in the testis, our findings suggest that OTA may be a cause of testicular cancer.

Acetaminophen induces xenobiotic-metabolizing enzymes in rat: Impact of a uranium chronic exposure

The extensive use of uranium in civilian and military applications increases the risk of human chronic exposure. Uranium is a slightly radioactive heavy metal with a predominantly chemical toxicity, especially in kidney but also in liver. Few studies have previously shown some effects of uranium on xenobiotic-metabolizing enzymes (XME) that might disturb drug pharmacokinetic. The aim of this study was to determine whether a chronic (9 months) non-nephrotoxic low dose exposure to depleted uranium (DU, 1 mg/rat/day) could modify the liver XME, using a single non-hepatotoxic acetaminophen (APAP) treatment (50 mg/kg). Most of XME analysed were induced by APAP treatment at the gene expression level but at the protein level only CYP3A2 was significantly increased 3 h after APAP treatment in DU-exposed rats whereas it remained at a basal level in unexposed rats. In conclusion, these results showed that a chronic non-nephrotoxic DU exposure specially modify CYP3A2 after a single therapeutic APAP treatment.

Effect of a 50-Hz electromagnetic field on the gene expression of glutathione S-transferase T1 (Gstt1) in the testis and liver of male rats

Glutathione S-transferases (GSTs) are a superfamily of dimeric proteins catalyzing the conjugation of glutathione with a wide variety of compounds and provide a strong antioxidant function by neutralizing electrophiles and free radicals. The subunits of the GSTs family are placed into several classes including theta (GSTθ). The aim of this study was to demonstrate the expression of Gstt1 (a member of GSTθ) gene in the testis and liver of rat in response to extremely low-frequency electromagnetic fields (ELF-EMF). After exposing male Wistar rats to the stressor (ELF-EMF 50 Hz, 500 µT) for 30 days, we quantified the gene expression of the Gstt1 by reverse transcription polymerase chain reaction in exposed and unexposed rats. Results indicated that the expression of Gstt1 in the liver and testis did not undergo any change at transcription level by environmental exposure to ELF-EMF at this duration and intensity.

The effects of prenatal alcohol exposure on the morphological characteristics of spinal motoneurons

Clinical studies and research in animals have established that alcohol consumption during pregnancy produces irreversible developmental anomalies. Deficits in fine motor performance are often noted in infants diagnosed with fetal alcohol syndrome. However, the effects of alcohol on the spinal motoneurons have not been examined. In this study, the morphometric alterations in spinal motoneurons were assessed as a result of prenatal alcohol exposure. Pregnant Sprague Dawley rats were administered with 1.0 ml of 20% ethyl alcohol per 100 gm body weight via intraperitoneal injections, and unexposed rats served as controls. Rats were perfused through the left cardiac ventricle and a complete laminectomy was performed. Spinal cord sections from the L4-5 segments were cut serially and stained for cresyl fast violet. Sections were also subjected to TUNEL assay for detection of apoptosis. Observations were made between 1 and 4 weeks after birth. Morphologic characteristics of motoneurons in the alcohol-exposed group of rats were altered. Counts and measurements revealed significant reduction in number and size of alcohol-exposed spinal motoneurons at all time points studied. Prenatal exposure to alcohol showed cytotoxic effects whereby it adversely affected both motoneuron growth and differentiation in utero.

Effects of rock wool on the lungs evaluated by magnetometry and biopersistence test.

BackgroundAsbestos has been reported to cause pulmonary fibrosis, and its use has been banned all over the world. The related industries are facing an urgent need to develop a safer fibrous substance. Rock wool (RW), a kind of asbestos substitute, is widely used in the construction industry. In order to evaluate the safety of RW, we performed a nose-only inhalation exposure study in rats. After one-month observation period, the potential of RW fibers to cause pulmonary toxicity was evaluated based on lung magnetometry findings, pulmonary biopersistence, and pneumopathology.MethodsUsing the nose-only inhalation exposure system, 6 male Fischer 344 rats (6 to 10 weeks old) were exposed to RW fibers at a target fiber concentration of 100 fibers/cm3 (length [L] > 20 μm) for 6 hours daily, for 5 consecutive days. As a magnetometric indicator, 3 mg of triiron tetraoxide suspended in 0.2 mL of physiological saline was intratracheally administered after RW exposure to these rats and 6 unexposed rats (controls). During one second magnetization in 50 mT external magnetic field, all magnetic particles were aligned, and immediately afterwards the strength of their remanent magnetic field in the rat lungs was measured in both groups. Magnetization and measurement of the decay (relaxation) of this remanent magnetic field was performed over 40 minutes on 1, 3, 14, and 28 days after RW exposure, and reflected cytoskeleton dependent intracellular transport within macrophages in the lung. Similarly, 24 and 12 male Fisher 344-rats were used for biopersistence test and pathologic evaluation, respectively.ResultsIn the lung magnetometric evaluation, biopersistence test and pathological evaluation, the arithmetic mean value of the total fiber concentration was 650.2, 344.7 and 390.7 fibers/cm3, respectively, and 156.6, 93.1 and 95.0 fibers/cm3 for fibers with L > 20 μm, respectively. The lung magnetometric evaluation revealed that impaired relaxation indicating cytoskeletal toxicity did not occur in the RW exposure group. In addition, clearance of the magnetic tracer particles was not significantly affected by the RW exposure. No effects on lung pathology were noted after RW exposure.ConclusionThese findings indicate that RW exposure is unlikely to cause pulmonary toxicity within four weeks period. Lung magnetometry studies involving long-term exposure and observation will be necessary to ensure the safety of RW.

Changes in sex hormones and offspring sex ratio following gasoline exposure in male rats

An experimental study was performed to determine the effect of gasoline inhalation on sex hormones and offspring sex ratio in male rats. Twenty two Sprague–Dawley adult male rats were divided into two groups. In the first group (n = 11), animals were exposed to gasoline vapor for 6 h daily for 30 consecutive days. The second group served as control without gasoline exposure. In the end of the study, sex hormones including total testosterone, luteinizing hormone and, follicle-stimulating hormone were determined using radioimmunoassay methods. Then, animals in both groups were mated with healthy unexposed female rats and sex of offspring was determined after birth. Results showed that the level of all sex hormones was significantly decreased in test group compared with control ones (P < 0.02). Offspring sex ratio was 0.39 (38/96) in the test group, significantly lower than 0.54 (60/101) in the control group (P = 0.03). The potential of manipulating offspring sex ratio through a simple, safe, and practical method would be an interesting subject. The results of the present study could provide a baseline for future research on this subject.

The effect of chronic lead acetate trihydrate intoxication in Wistar rats on experimental Ascaris suum infestation and immunity

Abstract SPF male Wistar rats were exposed for four months to lead acetate trihydrate present in drinking water (100 mg/l) and subsequently infested with 1000 ± 100 infective A. suum eggs. Metabolic activity of phagocytes and proliferative activity of T-lymphocytes were investigated on Day 4 and 8 after A. suum eggs infestation (Day 130 and 134 of lead acetate trihydrate exposition). The results demonstrated that treatment with lead acetate trihydrate led to increased susceptibility to infestation, manifested by increased average number of A. suum larvae in the lungs of exposed rats compared to unexposed ones. Moreover, migration of A. suum larvae on Day 8 was associated with significant increase in index of metabolic activity of phagocytes in unexposed rats in comparison with controls. In contrast, in rats exposed to the lead and infested by A. suum eggs a non-significant increase in the studied immunological parameters was recorded. Significant differences in immunological parameters were observed between unexposed, infested and infested and exposed groups of rats. In the unexposed group of animals Ascaris suum infestation caused a significant increase in the index of metabolic activity of phagocytes and stimulation index of lymphocytes in comparison with lead exposed rats.

Pulmonary Irritation After Inhalation Exposure to Benzalkonium Chloride in Rats

Benzalkonium chloride (BAC) is a quaternary ammonium compound (QAC) with a C8 to C18 chain length of alkyl groups. Since BAC exerts toxic effects on microorganisms, it has been used as an effective germicide and preservative, mostly in cosmetic industry and medicine. However, the toxic potential of BAC may be hazardous to humans, due to the common use of preparations containing BAC as a preservative. To assess the possible toxic effects of BAC, two-stage experiments were performed on female Wistar rats. At first, LC50 after a single exposure to BAC aerosol was determined. Then, the animals were exposed to BAC aerosol at 30 mg/m3 for 6 h, and for 3 days (6 h/day). The controls were unexposed rats. Directly after BAC exposure and 18 h afterwards, BALF concentrations were measured of total protein, Clara cell protein, matrix metalloproteinase-9 (MMP-9), hyaluronic acid (HA), immunoglobulin E (IgE) and cytokines (TF-alpha, IL-6 and MIP-20), lactate dehydrogenase (LDH) and GSH-S-transferase (GST). The LC50 value for exposed rats was ca. 53 mg BAC in m3 air for 4 h. All the rats survived single and repeated inhalation exposure to 30 mg/m3 BAC. After single and repeated exposure, lung weight, total protein, HA and LDH activity in BALF of exposed rats were higher than in controls while CC16 levels were decreased. A significantly higher BALF concentration of IL-6 and IgE was noted in animals exposed to single and repeated doses. BALF concentrations of MMP-9, TNF-alpha, and MIP-2 in exposed rats were similar to those in control animals. BAC may be classified to class I acute inhalation toxicity. It showed a strong inflammatory and irritant activity on the lungs after 6h inhalation and stimulated dynamic patterns of IL-6 and IgE production and protein infiltration from blood vessels to BALF. Continued exposure resulted in cellular destruction, a statistically significant increase in LDH activity and a continuous decrease in CC16 concentration in BALF.

Assessing the Potential Leukemogenic Effects of 50 Hz Magnetic Fields and their Harmonics Using an Animal Leukemia Model

To answer the still unresolved question of the possible leukemogenic effects of extremely low frequency magnetic fields (ELF-MFs) and of their harmonics on the incidence of B acute lymphoblastic leukemia in children, we used an animal model to explore the possible co-initiating or co-promoting effects of ELF-MFs on the development of leukemia. We used a rat model in which B acute lymphoblastic leukemia is chemically induced by a nitrosurea derivative. From the onset of the chemical treatment, the animals were also exposed to ELF-MFs (100 microT, sinusoidal 50 Hz MFs), with or without harmonics. The experiment was conducted on 280 rats. We compared body weight and survival time, percentage of bone marrow blast cells, cumulative incidence of leukemia and type of leukemia in the unexposed groups and in the groups exposed to 50 Hz MFs, with and without harmonics. The results showed no significant differences between exposed and unexposed rats for any of these parameters (p > 0.05). Significant changes in the leukemia type obtained after gamma-irradiation of the leukemia model, showed its sensitivity to a physical agent. Our results do not support the hypothesis that ELF-MFs, with or without harmonics, affect the development of B acute lymphoblastic leukemia in children.