Pleurotus cornucopiae (PC) mushrooms are found in the field and commonly known in Japan as Tamogidake mushrooms. The present study investigated the protective effects of an aqueous extract of PC on carbon tetrachloride (CCl4)-induced hepatotoxicity and the possible mechanism involved in this protection including cytochrome P450 (CYP) 2E1. Wistar rats were pretreated with aqueous extracts of PC (0, 100, 200, and 400 mg/kg) orally for 8 days prior to the intraperitoneal administration of a single dose of CCl4 (0.5 ml/kg) or corn oil. Pretreatment with PC mushroom extract significantly prevented the increased serum enzyme activities of alanine and aspartate aminotransferases in a dose-dependent manner, and suppressed the expression of CYP2E1. PC mushroom extract also protected hepatocytes from the damage effects of CCl4 as remarked by histological and electromicroscopical findings. It was concluded that repeated daily doses of aqueous extracts of PC mushroom reduced the toxic effects exerted by CCl4 on the liver.

This study was performed to examine whether the brain activities induced by noxious algesic chemical substances in anesthetized animals could be detected by blood oxygen-level-dependent functional magnetic resonance imaging (BOLD-fMRI). Multislice gradient echo images of the primary somatosensory cortex were obtained using a 7.05 T superconducting system and a one-turned surface coil centered over the primary somatosensory cortex of the 1.0%-isoflurane-anesthetized rat. The Z-score t-map of BOLD signals and its time-course analysis revealed that subcutaneous injection of formalin into the left forepaw immediately induced an early response in the contralateral primary sensory cortex lasting for a few minutes, followed by a late response until 20 min after stimulation. In contrast, injection of capsaicin into the left forepaw evoked only the early response. Furthermore, pretreatment with morphine completely abolished these responses induced by the chemical algesic substances. Thus BOLD-fMRI is a useful method to analyze the brain activities of painful stimulation in anesthetized animals.

To investigate the effect of the environmental pollutants, polycyclic aromatic hydrocarbons (PAHs), on retinoic acid-induced teratogenesis, all-trans-retinoic acid (RA) dissolved in corn oil (120 mg/kg) was administered orally to pregnant rats at the 11th day of gestation with and without the prior intraperitoneal treatment with 10 mg/kg 3-methylcholanthrene (3-MC) for 3 days. Dams were killed on the 20th day of pregnancy. The examinations of fetuses revealed that 3-MC barely enough to cause induction of P-450 in pregnant dams had profound embryo-toxic effects: the fetal resorption amounted to - 60% of total number of implantations. The fetuses survived weighed less than the control fetuses. All of RA-treated mothers had fetuses with abnormalities, and the main malformations were absence of tail (100%), caudal and sacral malformations (100%), and cleft palate (42%). Pregnant dams received both 3-MC and RA had a reduced severeness of tail anomaly (33%), while the rest, 67%, had short vestigial tail. Caudal and sacral malformations were detected but at a milder degree. We did not observe cleft palate in this group. The concurrent treatment of dams with 3-MC and RA led to an increased inducibility of cytochrome P-450 and subsequently, CYP1A1 dependent enzyme activity higher than those observed after the injection of 3-MC alone. UDP-glucuronyltransferase activity was also markedly induced in concurrent 3-MC and RA group higher than that in 3-MC alone. We suggest that the induction of P-450 and alteration of metabolic enzyme activities may play an important role in reducing the teratogenic potency of RA. However, RA-treatment did not retard the embryo-toxic effect of 3-MC but rather potentiated

This paper concerns somato-autonomic reflex responses in various visceral organs following somatic sensory stimulation in animals anesthetized to eliminate emotional factors. Various forms of somatic sensory stimulation can produce different autonomic reflex responses, depending on the visceral organs and which somatic afferents are stimulated. Some responses have a dominant sympathetic efferent involvement, whereas others have predominantly parasympathetic efferent involvement. Some responses have propriospinal and segmental characteristics, while others have supraspinal and systemic characteristics in their reflex nature. These somato-autonomic reflex responses may be functioning during physical therapy including acupuncture

The hooded phenotype is one of the coat color phenotype seen peculiarly in the rat. The hooded locus showing autosomal recessive inheritance is mapped to chromosome (Chr) 14 and that the hooded phenotype receives modification by hooded-modifier gene showing the linkage to the hooded locus. However, a gene responsible for either the hooded or hooded-modifier gene is not yet identified. To clarify genetic control of hooded phenotype, we carried out genetic linkage studies using BN and LEA rats. For determination of phenotypic variation, we measured ratio of pigmented coat area in parental and their Fsub(1) and Fsub(2) rats. We, then, conducted a genome-wide scan on 152 Fsub(2) rats for linkage with ratio of pigmented coat area for the dorsal, ventral and total regions. A major quantitative trait locus (QTL), D14Got40, showing highly significant linkage contributing 70-90% of the variance for hooded phenotype was detected on Chr 14, which may be correspondent to the hooded locus. In addition, another QTL, D17Rat2, showing highly significant linkage was also detected on Chr 17 in dorsal region phenotype as well as a QTL showing suggestive linkage on Chr15 in ventral region phenotype. We, further, investigated a genome-wide scan for epistatic interactions and detected significant interactions between D14Got40 and D20Mit1, and between D14Got40 and D17Rat2 in the dorsal region phenotype. These results suggest that a major QTL in Chr 14, which is possibly correspondent to the hooded locus, mainly regulates the hooded phenotype with some modifier loci, two of which show epistatic interactions with the hooded locus.

The health hazards of individual organophosphorus insecticides have been characterized by their acute toxicity, mainly by investigating their cholinesterase inhibition. However, the chronic effects of most of these toxicants on the drug-metabolizing enzymes have not been investigated. Profenofos (O-4-bromo-2-chlorophenyl O-ethyl S-propyl phosphorothioate) is an organophosphorus pesticide widely used in cotton cultivation. In the present study, we investigated the effect of profenofos on male-specific cytochrome P450 (CYP) enzymes in adult Wistar rats. We orally administered 17.8 mg/kg body weight, twice weekly for 65 days. Profenofos downregulated levels of hepatic and testicular CYP2C11 and CYP3A2 mRNA and protein expression. Testicular aromatase (CYP19A) mRNA was decreased in the profenofos-treated rats compared to controls. Overall, the present study suggests that profenofos acts as an endocrine disruptor of male-specific CYP enzymes and affects testosterone concentration, which implicates its deleterious effects on animal or human males chronically exposed to organophosphorus pesticide.

Nigella sativa (family Ranunculaceae ) is an annual plant that has been traditionally used on the Indian subcontinent and in Middle Eastern countries. In this study, we investigated the effect of N. sativa oil on the drug-metabolizing cytochrome P450 (CYP) enzymes and whether it has a protective effect against the acute hepatotoxicity of CCl4. Intraperitoneal injection of rats with CCl4 drastically decreased CYP2E1, CYP2B, CYP3A2, CYP2C11, and CYP1A2 mRNA and protein expressions. Oral administration of 1 ml/kg N. sativa oil every day for one week prior to CCl4 injection alleviated CCl4-induced suppression of CYP2B, CYP3A2, CYP2C11, and CYP1A2. Moreover, CCl4 increased iNOS and TNFalpha mRNA, while N. sativa oil administration for one week prior to CCl4 injection downregulated the CCl4-induced iNOS mRNA and up-regulated IL-10 mRNA. These results indicate that N. sativa oil administration has a protective effect against the CCl4-mediated suppression of hepatic CYPs and that this protective effect is partly due to the downregulation of NO production and up-regulation of the anti-inflamnatory IL-10.

FT-IR and ESR were used for on the investigation of the CCl4-induced peroxidation of rat liver microsomes in combination with biochemical methods. Lipid peroxidation was assayed by TBA reagent in the presence of CCl4 and NADPH. The CCl3 - radical was detected by ESR spectroscopy with a spin trapping reagent of PBN. The FT-IR spectroscopy revealed that absorption band of -C-H in -C=C-H decreased in intensity at 3012 cm(-1), but the absorption bands of the phosphate head and choline in the phospholipids did not significantly change between 1300 and 900 cm(-1). These findings were interpreted to be due to the removal of H- from -C=C-H by radicals as the first step of lipid peroxidation, and to the absence of dephosphorylation of phospholipids in the microsomal membrane. This is the first IR spectroscopic evidence indicating the nature of damage to a microsomal membrane caused by CCl4 treatment. The spectroscopies used here demonstrated that they are useful tools to observe the damage