Nrf2 Lowers the Risk of Lung Injury via Modulating the Airway Innate Immune Response Induced by Diesel Exhaust in Mice.

In the present study, we investigated the role of Nrf2 in airway immune responses induced by diesel exhaust (DE) inhalation in mice. C57BL/6J Nrf2+/+ and Nrf2-/- mice were exposed to DE or clean air for 8 h/day and 6 days/week for 4 weeks. After DE exposure, the number of neutrophils and macrophage inflammatory protein (MIP)-2 level in bronchoalveolar lavage fluid (BALF) and interleukin (IL)-17 level in the lung tissue increased in Nrf2-/- mice compared with Nrf2+/+ mice; however, the lack of an increase in the level of tumor necrosis factor (TNF)-α in the lung tissue in Nrf2+/+ mice and mild suppression of the level of TNF-α in Nrf2-/- mice were observed; the level of granulocyte macrophage colony-stimulating factor (GM-CSF) in the lung tissue decreased in Nrf2-/- mice than in Nrf2+/+ mice; the number of DE particle-laden alveolar macrophages in BALF were larger in Nrf2-/- mice than in Nrf2+/+ mice. The results of electron microscope observations showed alveolar type II cell injury and degeneration of the lamellar body after DE exposure in Nrf2-/- mice. Antioxidant enzyme NAD(P)H quinone dehydrogenase (NQO)1 mRNA expression level was higher in Nrf2+/+ mice than in Nrf2-/- mice after DE exposure. Our results suggested that Nrf2 reduces the risk of pulmonary disease via modulating the airway innate immune response caused by DE in mice.

Serotonin rebalances cortical tuning and behavior linked to autism symptoms in 15q11-13 CNV mice.

Serotonin is a critical modulator of cortical function, and its metabolism is defective in autism spectrum disorder (ASD) brain. How serotonin metabolism regulates cortical physiology and contributes to the pathological and behavioral symptoms of ASD remains unknown. We show that normal serotonin levels are essential for the maintenance of neocortical excitation/inhibition balance, correct sensory stimulus tuning, and social behavior. Conversely, low serotonin levels in 15q dup mice (a model for ASD with the human 15q11-13 duplication) result in impairment of the same phenotypes. Restoration of normal serotonin levels in 15q dup mice revealed the reversibility of a subset of ASD-related symptoms in the adult. These findings suggest that serotonin may have therapeutic potential for discrete ASD symptoms.

Nrf2 Regulates the Risk of a Diesel Exhaust Inhalation-Induced Immune Response during Bleomycin Lung Injury and Fibrosis in Mice.

The present study investigated the effects of diesel exhaust (DE) on an experimental model of bleomycin (BLM)-induced lung injury and fibrosis in mice. BLM was intravenously administered to both Nrf2+/+ and Nrf2-/- C57BL/6J mice on day 0. The mice were exposed to DE for 56 days from 28 days before the BLM injection to 28 days after the BLM injection. Inhalation of DE induced significant inhibition of airway clearance function and the proinflammatory cytokine secretion in macrophages, an increase in neutrophils, and severe lung inflammatory injury, which were greater in Nrf2-/- mice than in Nrf2+/+ mice. In contrast, inhalation of DE was observed to induce a greater increase of hydroxyproline content in the lung tissues and significantly higher pulmonary antioxidant enzyme mRNA expression in the Nrf2+/+ mice than in Nrf2-/- mice. DE is an important risk factor, and Nrf2 regulates the risk of a DE inhalation induced immune response during BLM lung injury and fibrosis in mice.

Sleep-disordered breathing and disorders of glucose metabolism.

AIMS: The authors identified the risk of disorders of glucose metabolism (DGM) for sleep-disordered breathing (SDB). METHODS: We conducted a cross-sectional study in 536 men aged 33-84 years. Patients with diabetes medication were excluded for the analysis and DGM were diagnosed by fasting plasma glucose≥100mg/dl and/or 2h plasma glucose ≥140mg/dl. RESULTS: The prevalence of DGM in subjects with and without severe SDB, which was judged by an apnea-hypopnea index (AHI) of 30, were 64.9% and 53.3%, which showed no significant difference. The adjusted odds ratios (ORs) (95% confidence intervals [CIs]) of the logarithmic-transformed AHI and that of C-reactive protein for DGM were 1.3 (0.87-2.0) and 2.3 (1.5-3.6), respectively. When the subjects were categorized by the severity of SDB, the ORs (95% CIs) of subjects with mild, moderate and severe SDB against subjects without SDB were 2.9 (1.8-4.6), 1.2 (0.72-2.1) and 1.5 (0.8-3.0), respectively. CONCLUSION: A significant association was observed between mild SDB and the presence of DGM in male subjects of this study.

Biological markers, lifestyles and metabolic syndrome in workers.

OBJECTIVE: The association between metabolic syndrome (MetS) and biological inflammatory or anti-coagulant markers were clarified in combination with lifestyle factors. PATIENTS AND METHODS: The target subjects were 5102 working men without metabolic diseases, aged 30-60 years old. The authors measured the serum levels of high-sensitivity C-reactive protein (CRP), uric acid and plasma fibrinogen as potential key biomarkers of MetS. RESULTS: Mean values of uric acid, log-transformed serum CRP and plasma fibrinogen increased significantly as the number of components of MetS increased after adjustment for age. Multivariate analysis revealed significant associations between the presence of MetS and age, habitual exercise, not current smoking, the log-transformed value of serum CRP and serum uric acid, with odds ratios (ORs) of 1.03 (95% confidence interval (CI): 1.02-1.04; p<0.001), 0.77 (95% CI: 0.65-0.90; p<0.01), 0.82 (95% CI: 0.70-0.96; p<0.05), 3.2 (95% CI: 2.6-3.9; p<0.001) and 1.5 (95% CI: 1.4-1.6; p<0.001), respectively for the presence of MetS. CONCLUSION: Elevated serum level of CRP, uric acid, not habitual exercise and current smoking were associated with MetS in this cross-sectional study.

Effect of smoking prevention education using improved tobacco smoke collection method.

OBJECTIVE: To verify the effect of smoking prevention education for nursing students using the improved tobacco smoke collection method. METHODS: The improved tobacco smoke collection method allows mainstream smoke and sidestream smoke from a cigarette to be separately extracted using a closed system. After collection, we performed gas measurement using a gas detection tube and the Schiff reagent method. We provided a lecture incorporating the experimental method for an experimental group (42 students), but only the lecture without the method for a control group (43 students). We surveyed the changes in The Kano Test for Social Dependence (KTSND) scores before and after the lecture and one month later. RESULTS: In the experimental group, the total scores of the KTSND were 10.2 ± 5.0 (mean ± standard deviation) before the lecture, 5.8 ± 4.1 after the lecture, and 6.9 ± 4.8 one month later. On the other hand, the scores were 10.7 ± 5.7, 7.5 ± 5.8, and 9.7 ± 5.5 in the control group before, after, and one month after the lecture, respectively. It is considered that the students understood "smoking is harmful to health" since this gas analysis method can be used to check for harmful gases visually. CONCLUSION: Result of this study suggest that this experimental method is useful for educating nursing students on the harmful effects of smoking.

Substrate specificity of human granzyme 3: analyses of the P3-P2-P1 triplet using fluorescence resonance energy transfer substrate libraries.

Granzyme 3 (Gr3) is known as a tryptase-type member of the granzyme family and exists in the granules of immunocompetent cells. Granule proteases including granzymes, are transported into the cytoplasm of tumor cells or virus-infected cells by perforin function, degrade cytoplasmic or nuclear proteins and subsequently cause the death of the target cells. Recently, although several substrates of Gr3 in vivo have been reported, these hydrolyzed sites were unclear or lacked consistency. Our previous study investigated the optimal amino acid triplet (P3-P2-P1) as a substrate for Gr3 using a limited combination of amino acids at the P2 and P3 positions. In the present study, new fluorescence resonance energy transfer (FRET) substrate libraries to screen P2 and P3 positions were synthesized, respectively. Using these substrate libraries, the optimal amino acid triplet was shown to be Tyr-Phe-Arg as a substrate for human Gr3. Moreover, kinetic analyses also showed that the synthetic substrate FRETS-YFR had the lowest Km value for human Gr3. A substantial number of membrane proteins possessed the triplet Tyr-Phe-Arg and some of them might be in vivo substrates for Gr3. The results might also be a great help for preparing specific inhibitors to manipulate Gr3 activity both in vitro and in vivo.

Asymmetric dimethylarginine is related to the predicted stroke risk in middle-aged Japanese men.

BACKGROUND: Asymmetric dimethylarginine (ADMA) has recently been investigated as a risk marker for cardio- and cerebrovascular diseases. However, whether ADMA levels are related to the risk of stroke in the Japanese general population remains unclear. METHODS: We examined 769 Japanese men (mean age, 47 ± 5 years) undergoing health examinations. Each subject's ADMA level and various vascular risk factors were assessed; the predicted 10-year stroke risk was calculated using the point-based prediction model from the Japan Public Health Center Study. RESULTS: In a multiple linear regression analysis, age, body mass index, estimated glomerular filtration rate, and current smoking status were significant independent determinants of ADMA levels. A significant odds ratio (OR) for high predicted stroke risk (10-year risk ≥ 5%)was noted in the highest quartile of ADMA levels (OR, 2.47; 95% CI, 1.002-6.07), compared with the lowest quartile, after adjusting for potential confounding factors. A significant OR for high predicted stroke risk was also found for each standard deviation increment in ADMA level (adjusted OR, 1.46; 95% CI, 1.10-1.92). CONCLUSION: Elevated ADMA levels were significantly associated with an increased predicted stroke risk, suggesting that measuring ADMA levels may be useful for identifying middle-aged Japanese men with a high risk of stroke.

Corticosterone facilitates fluoxetine-induced neuronal plasticity in the hippocampus.

The hippocampal dentate gyrus has been implicated in a neuronal basis of antidepressant action. We have recently shown a distinct form of neuronal plasticity induced by the serotonergic antidepressant fluoxetine, that is, a reversal of maturation of the dentate granule cells in adult mice. This "dematuration" is induced in a large population of dentate neurons and maintained for at least one month after withdrawal of fluoxetine, suggesting long-lasting strong influence of dematuration on brain functioning. However, reliable induction of dematuration required doses of fluoxetine higher than suggested optimal doses for mice (10 to 18 mg/kg/day), which casts doubt on the clinical relevance of this effect. Since our previous studies were performed in naive mice, in the present study, we reexamined effects of fluoxetine using mice treated with chronic corticosterone that model neuroendocrine pathophysiology associated with depression. In corticosterone-treated mice, fluoxetine at 10 mg/kg/day downregulated expression of mature granule cell markers and attenuated strong frequency facilitation at the synapse formed by the granule cell axon mossy fiber, suggesting the induction of granule cell dematuration. In addition, fluoxetine caused marked enhancement of dopaminergic modulation at the mossy fiber synapse. In vehicle-treated mice, however, fluoxetine at this dose had no significant effects. The plasma level of fluoxetine was comparable to that in patients taking chronic fluoxetine, and corticosterone did not affect it. These results indicate that corticosterone facilitates fluoxetine-induced plastic changes in the dentate granule cells. Our finding may provide insight into neuronal mechanisms underlying enhanced responsiveness to antidepressant medication in certain pathological conditions.

EM, EM703 inhibit NF-kB activation induced by oxidative stress from diesel exhaust particle in human bronchial epithelial cells: importance in IL-8 transcription.

Diesel exhaust particle (DEP) is the major components of PM2.5, and much attention has focused on PM2.5 in relation to adverse health effects, and many pulmonary diseases. In the present study, we used a human bronchial epithelial cell (HBEC) line to investigate the anti-inflammatory effects of erythromycin (EM) and EM703 - a new derivative of erythromycin without antibacterial effects on the expressions of IL-8 caused by DEP exposure. DEP showed a dose-dependent stimulatory effect on IL-8 product in HBEC. Increases of IL-8 expression by DEP stimulation were significantly blocked by both EM and EM703 pretreatment. Furthermore, NF-κB and Nrf2 activation, the antioxidant enzymes such as HO-1, NQO-1 mRNA expression were increased by DEP exposure and these increases were blocked by both of EM and EM703 pretreatment. Our results suggest that, EM and EM703 may have an inhibitory effect on expression inflammatory cytokines in HBEC induced by DEP not only as an anti-inflammation but also an antioxidant drug. EM and EM703 might contribute to chemical prevention of the risk of pulmonary diseases induced by oxidative stress from environmental pollutant, such as DEP.

Early intervention with fluoxetine reverses abnormalities in the serotonergic system and behavior of rats exposed prenatally to dexamethasone.

Many psychiatric disorders emerge after adolescence. Among a variety of predisposing factors, prenatal stress has been thought to cause the symptoms of anxiety disorders. We recently reported that prenatal dexamethasone (DEX) exposure, which mimics some aspects of prenatal stress, induced anxiety-related behaviors in male offspring when they reached adulthood. Before the emergence of behavioral changes, abnormalities occurred in the hypothalamic-pituitary-adrenal axis during postnatal development. In the present study, we found abnormalities in serotonin (5-HT) signaling, including decreased expression of 5-HT(1A) receptor (5-HT(1A)-R) mRNA in the medial prefrontal cortex (mPFC) and 5-HT content in the hippocampus at postnatal week (PW) 4. These results support using early therapeutic interventions with serotonergic drugs to prevent late-emerging anxiety symptoms. To test this hypothesis, we treated rat pups born to DEX-administered mothers with fluoxetine (FLX), a selective serotonin reuptake inhibitor commonly used as an anti-anxiety medication, via breast milk from postnatal day (PD) 2-21. Anxiety-related behaviors examined at PW11-13 were not observed in the prenatally DEX-exposed offspring that were treated with FLX. Likewise, FLX increased 5-HT concentrations in the mPFC and ventral hippocampus at PW3 and normalized 5-HT(1A)-R mRNA concentrations in the mPFC at PW4. The decrease in brain-derived neurotrophic factor (BDNF) protein in the mPFC and dorsal hippocampus was also restored at PW4. Furthermore, administration of the 5-HT(1A)-R full agonist (R)-(+)-8-hydroxy-2-(di-n-propylamino)tetralin from PD2 to 21 also prevented the emergence of behavioral abnormalities in the prenatally DEX-exposed offspring, implicating the involvement of 5-HT(1A)-Rs in the neonatal FLX effect. Collectively, an early pharmacological intervention to normalize serotonergic transmission effectively suppressed the emergence of symptoms induced by prenatal DEX exposure in rats.

The effect of sleep restriction and psychological load on the diurnal metabolic changes in tryptamine-related compounds in human urine.

OBJECTIVE: The effect of a severely stressful situation (sleep restriction and psychological load) on the diurnal changes in novel tryptamine-related compounds (hydroxydiacetyltryptamine, sulphatoxymelatonin, and dihydromelatonin) was evaluated in human subjects for 16 days. METHODS: The subjects were allowed to sleep for 5 h on days three through 12 and for 8 h on the other days. On days three through 12, the subjects were asked to perform a psychological task. The first two and the last 4 days were viewed as control days. A performance test was administered to evaluate the extent of the subjects' fatigue. Total urine was sampled by collecting it into bottles three times a day [(1) during the sleeping period, (2) in the morning, and (3) in the afternoon]. Seven tryptamine-related compounds in urine were assayed using HPLC-fluorometry. RESULTS: The urine melatonin level was high at night and low during the day. In contrast, urinary levels of hydroxydiacetyltryptamine and sulphatoxydiacetyltryptamine were low at night and high during the day. Dihydromelatonin was undetectable in urine during the sleeping period. Sleep restriction and psychological load did not affect diurnal changes in urinary melatonin, hydroxydiacetyltryptamine, sulphatoxydiacetyltryptamine, or N-acetylserotonin levels. The concentrations of hydroxymelatonin and sulphatoxymelatonin in urine did not show diurnal changes and decreased gradually during the experimental days. A principal component analysis confirmed the diurnal changes and suggested two novel metabolic pathways: (1) N-acetylserotonin to sulphtoxydiacetyltryptamine via hydroxydiacetyltryptamine, and (2) melatonin to dihydromelatonin. CONCLUSION: Severely stressful situations did not affect diurnal changes in melatonin, hydroxydiacetyltryptamine, sulphatoxydiacetyltryptamine, or N-acetylserotonin levels in urine.

Acute effects of walking in forest environments on cardiovascular and metabolic parameters.

We previously found that forest environments reduced stress hormones such as adrenaline and noradrenaline and showed the relaxing effect both in male and female subjects. In the present study, we investigated the effects of walking under forest environments on cardiovascular and metabolic parameters. Sixteen healthy male subjects (mean age 57.4 ± 11.6 years) were selected after obtaining informed consent. The subjects took day trips to a forest park in the suburbs of Tokyo and to an urban area of Tokyo as a control in September 2010. On both trips, they walked for 2 h in the morning and afternoon on a Sunday. Blood and urine were sampled on the morning before each trip and after each trip. Blood pressure was measured on the morning (0800) before each trip, at noon (1300), in the afternoon (1600) during each trip, and on the morning (0800) after each trip. The day trip to the forest park significantly reduced blood pressure and urinary noradrenaline and dopamine levels and significantly increased serum adiponectin and dehydroepiandrosterone sulfate (DHEA-S) levels. Walking exercise also reduced the levels of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) and urinary dopamine. Taken together, habitual walking in forest environments may lower blood pressure by reducing sympathetic nerve activity and have beneficial effects on blood adiponectin and DHEA-S levels, and habitual walking exercise may have beneficial effects on blood NT-proBNP levels.

Depressive state and subsequent weight gain in workers: A 4-year follow-up study.

OBJECTIVE: It has been suggested that the presence of a depressive state is a predictor of increase of the body weight. However, to precisely understand the nature of this relationship, the data should be controlled for other factors that can also be associated with weight gain. METHODS AND PARTICIPANTS: To test the hypothesis that the presence of a depressive state is associated with future weight gain, a 4-year prospective occupation-based cohort study was conducted in male adult workers (N=1730) at a railway company. Following the initial screening, follow-up information was obtained via a legally required annual health examination. The presence of a depressive state was identified using the Zung Self-Rating Depression Scale (SDS). The weight of each participant was measured to the nearest kilogram. Multiple logistic regression analysis was used to test the association between the depressive state and a weight gain of 4 kg or more over the 4-year study period after controlling for potentially confounding variables such as the age, smoking status, alcohol intake status, and physical activity. RESULTS: A weight gain of 4 kg or more over the 4-year study period was significantly associated with the depressive state, even after controlling for confounding variables (p< 0.05). Short-term longitudinal analysis also revealed an association between the depressive state and subsequent increase of the body weight. CONCLUSION: Since the depressive state was demonstrated to be an important risk factor for increase of the body weight, further research on depression should be conducted with a view to providing effective health education.

The alcohol use disorders identification test: reliability study of the Japanese version.

Alcohol abuse is recognized as a major health issue, and early detection of alcohol abuse is very important. The alcohol use disorders identification test (AUDIT) has been widely used as a specific tool for its detection. We conducted a cross-sectional survey of Japanese male workers to validate the Japanese version of this test. The Japanese version of AUDIT also contains 10 questions. A score greater than or equal to 11 was considered as indicative of serious alcohol abuse or dependence. A total of 168 subjects took part in the survey, and 145 of these subjects sent in their responses to the questionnaire. Among these 145 subjects, there were 136 men. The average age of these male subjects was 38.2 years (±9.9). Among the 136 male subjects, 113 returned completely filled-in questionnaires. There were no significant differences in the mean values of the AUDIT score, short version of AUDIT (AUDIT-C) score, or age between the subjects who did or did not indicate their names in the questionnaire. The internal reliability (Cronbach alpha) of AUDIT was 0.67 for the total subject population and 0.45 for the subjects who indicated their names in the questionnaire (n=69). Cronbach's alpha of AUDIT-C was 0.51 for the total subject population and 0.43 for the subjects who indicated their names in the questionnaire. The Spearman's rho between AUDIT and AUDIT-C was 0.92 (P<.01), and the percentage of subjects with an AUDIT score greater than or equal to 11 was 8.0% (9/113). Thus, the Japanese version of AUDIT showed satisfactory internal reliability. AUDIT is easy to use and is useful for the detection of alcohol-related problems in occupational workers.

Relationship among lifestyles, aging and psychological wellbeing using the General Health Questionnaire 12-items in Japanese working men.

INTRODUCTION. The relationship among lifestyle, aging and psychological wellbeing was evaluated in Japanese working men. METHODS. Self-administered questionnaire on six lifestyle factors and the General Health Questionnaire 12-item version (GHQ12) were administered to 3306 male workers. Health practice index (HPI) was calculated as a desirable lifestyle score by summing up each binary lifestyle score (0, 1), ranging from 0 to 6. To check validity of the study outcome, the authors repeated twice with 1 year interval. HPI was categorised into three groups by the score of 0-2, 3-4 and 5-6. RESULTS. The number of subjects categorised by HPI was 532, 1967 and 807, respectively. The mean value of GHQ12 significantly decreased as the HPI increased by adjusting age. Multiple regression analysis was conducted to predict GHQ12 by six lifestyle scores, and age, sleep, night snacking and exercise were significantly related to GHQ12. Multiple logistic regression analysis was conducted and age in 50s, two-shift work, sleep, night snacking and exercise were significantly associated with GHQ12. CONCLUSION. Although cause-effect relationship cannot make clear, some of desirable health practices and aging were closely related to psychological wellbeing judged by GHQ12.

Serum insulin is significantly related to components of the metabolic syndrome in Japanese working women.

BACKGROUND: The aim of this study was to examine the association between serum insulin levels and components of the metabolic syndrome (MetS) in working women. METHODS: The target subjects were 141 working women. Serum triglyceride, HDL cholesterol, uric acid, plasma insulin and plasma glucose were measured in addition to waist circumference and blood pressure. RESULTS: MetS was diagnosed based on the modified criteria of the International Diabetes Federation, and was present in 7.1% (10/141) of the study subjects. Stepwise multiple regression analysis showed that some components of MetS were significantly associated with log-transformed values of the serum insulin. The standardized regression coefficient for the waist circumference, high density lipoprotein cholesterol, systolic blood pressure and age were 0.238, -0.333, 0.309 and -0.156, respectively. CONCLUSIONS: A statistically significant relationship existed between the components of MetS and the serum insulin levels in working women.

Optimal cut-off levels of body mass index and waist circumference in relation to each component of metabolic syndrome (MetS) and the number of MetS component.

AIMS: There is an ethnic difference of obesity index to diagnose metabolic syndrome. The authors explored the optimal cut-off levels for body mass index (BMI) and waist circumference (WC) in relation to each component of metabolic syndrome. MATERIALS AND METHODS: Receiver operating characteristics (ROC) analysis was used to determine the optimal cut-off levels for each component of metabolic syndrome. This study included 4572 workers aged 42.5±9.9 years. RESULTS: The optimal BMI cut-off values for diabetes mellitus, hypertension or dyslipidemia varied from 23.0 to 24.3 kg/m(2). As for WC, the optimal cut-off values varied from 83.0 to 83.7 cm. The optimal BMI cut-off values relating with one to three components of metabolic syndrome varied from 23.2 to 25.3 kg/m(2). As for WC, the optimal cut-off values varied from 83.0 to 85.0 cm. Pair-wise comparison of ROC curves showed that WC has an advantage in relation to metabolic syndrome and its components compared with BMI. By logistic regression analysis, odds ratios of obesity indices for hypertension, dyslipidemia or the number of metabolic component were all significantly increased. As for diabetes mellitus, odds ratios of BMI ≥25 and WC ≥85 significantly increased, respectively. CONCLUSIONS: Japanese criteria of obesity in metabolic syndrome in man may be appropriate for diabetes mellitus. Ethnic difference in criteria of obesity in Asian metabolic syndrome exists, and mutual comparisons in the prevalence of metabolic syndrome have a difficulty to conduct.

Effect of oral exposure to fenitrothion and 3-methyl-4-nitrophenol on splenic cell populations and histopathological alterations in spleen in Wistar rats.

Fenitrothion (FNT) is used throughout the world as an insecticide in agriculture. To investigate the effect of FNT on the splenocytes and the underlying mechanism, FNT and its main metabolite, 3-methyl-4-nitrophenol (MNP), were administered orally to Wistar rats in daily doses of 0, 5 and 10 mg/kg, 4-5 days/week for 9 weeks. Splenocytes were harvested from control and exposed rats, and the following cell phenotypes were quantified by flow cytometry: (1) B cells (PE-CD45RA), (2) T cells (FITC-CD3), (3) T cell subsets (PE-CD4 and PerCPCD8), (4) natural killer (NK) cells (FITC-CD161a), (5) macrophages (FITC-CD11b), and (6) granulocyte (PE-granulocyte). Body weight, weight of the spleen, and histopathological alterations of spleens were also examined. The percentage of splenic CD8+ T cells and the ratio of CD8/CD4 in the group receiving 10 mg/kg FNT, and the percentages of splenic CD3+ and CD8+ T cells in the group receiving 10 mg/kg MNP were significantly decreased compared with those in the controls. FNT exposure also significantly decreased the weight of the spleen and body weight. In addition, apoptotic lymphocytes in spleen were observed in FNT-exposed rats under transmission electron microscope. However, FNT and MNP exposures did not affect splenic NK cells, B cells, macrophages, and granulocytes. The above findings indicate that FNT and MNP may selectively affect splenic T cells in rats.