Galactosamine is known to induce hepatic injury in rats and the galactosamine-induced hepatitis is believed to be similar to viral hepatitis both morphologically and functionally. In the present study, we examined how drinking green tea affects the gene expression of inflammatory cytokines which may be up-regulated in galactosamine-induced hepatitis. As has been reported, galactosamine caused hepatic injury in rats as evidenced by an increase in serum transaminase activities and histological observations of the liver. The results of the reverse transcription and polymerase chain reaction indicated an increased gene expression of inflammatory cytokines, tumor necrosis factor-α and interleukin-1β, in the injured liver and the enzyme linked immunoassay showed an increase in the serum levels of these cytokines. Oral administration of green tea rich in catechins (Healthya green tea) restored these biomarkers in the galacotsamine-treated rats to near the control levels. These results suggest that the drinking of green tea with a high catechin content may help to prevent and/or attenuate the development of a certain type of hepatitis.
Dried plums, considered a healthy food in the West and used as medicine in India, contain phenolic compounds with protective actions against age-related diseases. Effects of oral plum ekisu (concentrated juice) on lipid and glucose tolerance were assessed in insulin-resistant obese Wistar fatty rats. Plum ingestion decreased blood glucose (P < 0.05) and plasma triglyceride concentrations (P < 0.01) compared with controls. Plum treatment for 2 weeks reduced areas under the curve (AUCs) for glucose and insulin during a glucose tolerance test. In db/db mice, plum decreased these AUCs, and also blood glucose during an insulin tolerance test. Plum treatment significantly increased plasma adiponectin concentrations and PPARγ mRNA expression in adipose tissue from Wistar fatty rats. Plum thus may increase insulin sensitivity in these rats via adiponectin-related mechanisms.
Previous studies have demonstrated that systemic administration of a low dose of the alpha2-adrenoceptor antagonists stimulates the ejaculatory response of male dogs, when this function is analyzed using the amount of ejaculated semen in response to genital stimulation. The present study was designed to further examine the features of the stimulatory effects of the alpha2-adrenoceptor antagonists on ejaculation, especially the duration of action. Treatment with yohimbine (0.1 mg/kg, i.p.) to male dogs, at 0.5, 1, 3, or 5 h before the testing, produced a significant stimulatory effects on the ejaculatory response elicited by manual penile stimulation; the amount of ejaculated semen was increased and the onset of ejaculation was shortened following each treatment. However, such effects were not observed in the treatment with yohimbine at 8 and 24 h before the testing, indicating that the ejaculatory stimulation induced by yohimbine lasted for a relative long period. By contrast, the stimulatory effects of RX821002 (0.1 mg/kg, i.p.), a selective alpha2-adrenoceptor antagonist, on ejaculation were observed only for 1 h after administration. To determine the contribution of the alpha2-adrenoceptor blockade for the long-lasting effect of yohimbine, we tested whether yohimbine can prevent the ejaculatory inhibition induced by clonidine, an alpha2-adrenoceptor agonist. The ejaculatory inhibition (a decrease in the amount of ejaculated semen and a delay onset of ejaculation) elicited by clonidine (0.05 mg/kg, i.p.; 1 h before testing) was completely blocked by pretreatment with yohimbine at 1 or 5 h before the testing, whereas the pretreatment with the drug at 24 h before the testing did not affect the clonidine-induced ejaculatory inhibition. These results indicate that yohimbine-induced ejaculatory stimulation is continued for a relative long period (at least 5 h after administration), and this long-lasting effects may be related to the alpha2-adrenoceptor blocking property of the drug.
Normally, bimolecular reactions are analyzed in terms of the Smoluchowski theory. However, when one attempts to generalize this analysis to cases where diffusion proceeds in two other than in three dimensions, one soon encounters severe conceptual difficulties. Although kinetic studies of membrane enzymes are generally difficult because the usual kinetic formalism refers to nonaggregated homogenous solutions, a major goal of our research is to define the molecular mechanism(s) by which alterations in membrane-bound substrate contents affect the enzyme activity in the same membrane. For that purpose, a simplified random-walk model was adopted in the present work. The enzyme reaction in the two-dimensional membrane could be calculated theoretically by applying the classical analysis of heat equation. As a result, the theoretical rate equation well accounting experimental findings was derived on the model of the liver microsomal NADHcytochrome b5 reductase reaction. Furthermore, it was found that the modification of the simple rigid-sphere collision theory by including a term called the steric factor was not necessary in this derived equation.
Short-chain fatty acids in the intestinal lumen affect colonic cell proliferation as well as function as an energy source for intestinal epithelial cells. A novel transporter of monocarboxylates, Slc5a8, is expressed abundantly in the colon, where it may participate in the Na+-coupled absorption of short-chain fatty acids produced by bacterial fermentation of dietary fiber. The present study examined the cellular localization of Slc5a8 in the murine gastrointestinal tract and kidney by in situ hybridization and immunohistochemistry. The hybridization signals were recognized in the terminal ileum and whole length of the large intestine, and were especially intense in the distal colon and rectum. The immunoreactivity of Slc5a8 was restricted to the striated border (the brush border) of enterocytes, and was not present in goblet cells, Paneth cells, or lamina propria cells. In the kidney, proximal tubules of both the cortex and the outer stripe of the outer medulla intensely expressed Slc5a8 mRNA, while the distal portions, including the loop of Henle, lacked the signals. The renal Slc5a8 immunoreactivity was localized only in the brush border of proximal tubules, not along the basolateral membrane. Thyroid follicular cells were immunoreactive for Slc5a8, with predominant labeling on the apical membrane. No other organs, including the esophagus, stomach, liver, pancreas, and salivary glands contained any notable signals of Slc5a8. These findings on the cellular and subcellular localization of Slc5a8 under normal conditions are helpful for understanding the physiological and pathological roles of Slc5a8.
To understand the molecular basis of inflammation-induced neurotrophic influences, we investigated the effects of lipopolysaccharide (LPS) on production of glial cell line-derived neurotrophic factor (GDNF) in the injured rat spinal cord or in cultured rat macrophages in comparison with the effects on synthesis/secretion of inducible nitric oxide synthase (iNOS) and nitric oxide (NO). We found that GDNF mRNA expression lasted longer than that of iNOS mRNA in the injured spinal cord after injection of the high-dose LPS that had improved locomotor function, suggesting that the GDNF expression and its balance with NO generation were critical for injury regeneration. Therefore, we next investigated the effects of LPS on cultured macrophages. Levels of iNOS mRNA and secreted NO were enhanced by LPS at lower concentrations (10 ng/mL and above), whereas mRNA expression and secretion of GDNF were elevated only at higher concentrations (100 ng/mL and above). The culture medium of macrophages treated with 10 ng/mL of LPS was actually neurotoxic against cultured cortical neurons, whereas that conditioned at 1000 ng/mL was not. These observations suggest that neurotoxicity partly based on NO is induced by a lower degree of inflammation, whereas neurotrophic effects based on GDNF are manifested at a higher degree of inflammatory activity.