The influences of inhaling particulate air-pollutants on hematopoiesis and myocardial oxidative stress were investigated in mice by intratracheal instillation (IT) of diesel exhaust particles (DEP), its dichloromethane soluble-component (DMSC) or residual particle-component (RPC). After IT, time courses of cytokine levels in bronchial alveolar lavage fluid (BALF), peripheral blood cell count, myocardial myeloperoxidase (MPO) activity and myocardial chemokine levels were observed for 24 hr. RPC caused sustained blood neutrophilia while that caused by DEP and DMSC was transient. RPC also caused sustained elevations of granulocyte colony-stimulating factor (G-CSF) and interleukin (IL)-6 levels in BALF. Furthermore, IL-1beta level in BALF in the RPC group was significantly elevated at 24 hr after IT. Significant positive correlations were observed between blood neutrophil count and IL-6/G-CSF levels in BALF. MPO activity in the myocardium was increased by RPC at 12 and 24 hr after IT while the activities in the kidney and the liver were not affected. Significant correlation was also observed between myocardial MPO activity and blood neutrophil count at 12 hr after IT, for all three substances. From these results, it was concluded that particle component of DEP may enhance myocardial oxidative stress via blood neutrophilia and the elevation of cytokine levels in BALF.
Dietary rapeseed (canola) oil (CO) given as the only fat nutrient shortens life in stroke-prone spontaneously hypertensive rats (SHRSP), compared with SHRSP given soybean oil (SO) instead of CO. CO ingestion increases plasma lipids and causes renal lesions in SHRSP and in spontaneously hypertensive rats (SHR), and increases plasma lipids also in Wistar Kyoto (WKY) rats, a normotensive counterpart of SHR. This study examined whether or not such unfavorable effects of CO are restricted to these closely related strains. For this purpose Wistar rats, the strain from which these strains were derived, were fed a diet containing 10% CO or SO as the sole fat nutrient for 10 weeks, and changes in clinical signs, urinalysis, blood biochemistry and pathology were compared. CO ingestion did not induce any abnormalities in Wistar rats, except significant increases in plasma concentrations of aldosterone and Na(+), compared with the SO group. Thus, the unfavorable effects of CO ingestion appear to be restricted to SHRSP and its closely related strains. The role of increased aldosterone and Na(+ )in the unfavorable events caused by CO in SHRSP, SHR and WKY rats, and any factors which could induce such increases in aldosterone and Na(+), remain to be elucidated.
The occurrence of trigeminal nerve tumors (TNTs) induced by neonatal administration of N-ethyl-N-nitrosourea (ENU) in WF × LE F1 (F1 rats was studied with special reference to sex difference, effect of gonadectomy and estradiol (E2) administration. Experimental groups 1–6 were treated with 40 mg ENU/kg of body weight neonatally. They consisted of male, female, castrated male, ovariectomized female, E2 pellet (0.1 mg, s.c.) supplemented and gonadectomized male and female rats respectively. Rats of groups 7–12 served as the respective controls without ENU. All the rats were killed at 8 months of age. Levels of serum E2 and E2 receptor (ER) of the TNTs were also examined. It was noted that the incidence of TNT was higher in males (79%) than in females (48%, P < 0.05) and did not change by castration in males (91%) but increased in ovariectomized female rats (74%, P < 0.05). Administration of E2 followed by gonadectomy inhibited the occurrence of TNTs in male rats (59%) but not in female rats (60%). No TNT was observed in any control groups. Kidney tumors were the second most frequent tumors next to nervous system tumors in the present experiment. The incidence of kidney tumors was much higher in females (38%) than in males (4%, P < 0.05) and decreased by ovariectomy, whereas it increased in male rats by E2 administration. ER levels of TNTs and trigeminal nerve tissue were < 1 fmol/mg protein. These results suggest that in rats treated with ENU neonatally, E2 has an inhibitory effect on the induction of TNTs but may not be regulated through ER. E2 also shows a promoting effect on kidney tumorigenesis.
The abilities of sn -1,2-didecanoylglycerol ( sn -1,2-DDG) to induce epidermal ornithinedecarboxylase (ODC) activity and epidermal hyperplasia were tested using SENCAR, DBA/2 and C57BL/6 mice. Following a single application of 5000 nmol of sn -1,2-DDG, ODC activity reached a maximum at 4 h after treatment with a peak activity of 6.03 nmol CO 2 /6mg protein/60 min in C57BL/6, 1.50 in SENCAR and 0.73 in DBA/2, respectively. The time course and magnitude for induction of ODC activity after multiple treatments was very similar to that after a single application in these three mouse lines. Interestingly, the induced ODC activityin C57BL/6 was always higher than that in SENCAR and DBA/2 mouse epidermis regardless of the treatment protocol. Induction of hyperplasia and dark basal keratinocytes (DCs) and changes in the labeling index (LI) of basal keratinocytes in DBA/2 and C57BL/6 mice following treatment with sn -1,2-DDG were investigated. Multiple treatments (twice weekly for 2 weeks) of 5000 nmol sn -1,2-DDG did not induce substantial increases inepidermal thickness or DCs 24 or 48 h after the last treatment. In contrast, TPA induced a marked increase in epidermal thickness in DBA/2 rather than CS7BL/6 and a considerably higher induction of DCs in DBA/2 (37.3 ± 2.2%) than in CS7BL/6 (9.6 ± 2.5%) 48 h after the last treatment. The LIs after topical application of sn -1,2-DDG were elevated at 24 h, but returned to basal levels by 48 h in both strains, whereas TPA treatment significantly elevated the LI In both strains at 48 h after the last application. In addition, the effects of various doses and frequencies of application of sn -1,2-DDG were investigated using SENCAR mice. Highdoses (20 000 nmol) or more frequent applications (5000 nmol once daily for 7 days) of sn -1,2-DDG still produced only weak hyperplasia. These results suggest that the induction of epidermal ODC activity can be dissociated from the induction of epidermal hyperplasia and may provide an explanation for the lack of complete promoting activity presently observed with membrane permeable diacylglycerol derivatives.
OBJECTIVE: A preliminary in vitro study with hepatocyte culture showed that concentrations as low as 10 µg/mL of PN‐M001 are able to significantly mitigate CCl4 hepatocyte damage ( P < 0.05) comparable to 100 µg/mL silymarin, and 100 µg/mL proved to be more protective than either silymarin 100 µg/mL or glycyrrhizin 10 µg/mL ( P < 0.05). METHODS: Wistar rats were allocated into three groups: (A) 0.1 mL/100 g body weight (BW) mixture of CCl 4 in olive oil (1 : 1 v/v) subcutaneous injection twice daily for 4 weeks; (B) as A, plus oral administration of 50 mg/kg of K‐17.22 dissolved in 5% glucose; (C) as B but with PN‐M001 given 1 week after the first injection of CCl 4 . Rats were killed at the end of the study and blood and liver samples were obtained. RESULTS: When compared with a control, group A showed a significant decrease of glutathione (GSH;>45%, P < 0.001) and oxidized GSH (GSSG; P < 0.01) liver content, a lower liver wet weight ( P < 0.01) together with an increase of both transaminases (>15‐fold, P < 0.001) whereas groups B and C both showed only a mild increase in transaminases (<4‐fold, P < 0.05). Group A showed a significant decrease of Y‐protein fraction and of GST activity, as tested by both substrates ( P < 0.01 vs control). However, both these parameters were reverted to normal by PN‐M001 ( P < 0.05 vs A). CONCLUSIONS: These preliminary data suggest that PN‐M001 exerts a highly protective and prolonged effect (either preventive or therapeutic) on GSH depletion in CCl 4 ‐induced liver injury, which suggests its potential use in the clinical setting.
It has been reported that the administration of butyrate, a short-chain fatty acid produced by microbiota in the intestine, induces expression of the genes involved in peroxisomal fatty acid b-oxidation. In the present study, we investigated whether administration of the butyrate-producing probiotics (Clostridium butyricum MIYARI 588, MYR) inhibit the progression of obesity and studied the effect of added dietary fiber and the mechanism in lipid metabolism. Male C57BL6J-ob/ob mice were divided into 3 groups, Control, MYR and inulin (INU) groups. Animals in MYR and INU groups were fed diet containing 3% MIYARI 588 ad libitum. Drinking water for INU group were added 1% inulin. Last week of the 7-week administration period, oral glucose-tolerance test was performed. The relative weights of liver and white adipose tissues (WAT) in MYR and INU groups were lower than Control group. Compared with Control group, Adiponectin expression in WAT of MYR group was tended to be higher, and that of MYR group was higher. In conclusion, it is suggested that the 7-week administration of MYR induces the changes in lipid metabolism involved in adiponectin expression in WAT accompanied by the decreases in liver and WAT weight.
