Influence of glutathione-S-transferase theta (GSTT1) and micro (GSTM1) gene polymorphisms on the susceptibility of hepatocellular carcinoma in Taiwan.

BACKGROUND AND OBJECTIVES: Hepatocellular carcinoma (HCC) is one of the most frequent malignant neoplasms worldwide and is the second leading cause of cancer death in Taiwan. Genetic polymorphism has been reported as a factor for increased susceptibility of HCC. Glutathione-S-transferases theta (GSTT1) and micro (GSTM1) play essential roles in detoxification of ingested xenobiotics and modulation of the susceptibility of gene-related cancer. The aim of this study was to estimate the relationships between these two gene polymorphisms and HCC risk and clinicopathological status in Taiwanese. METHODS: Polymerase chain reaction (PCR) was used to determine gene polymorphisms of 102 patients with HCC and 386 healthy controls. RESULTS: Both gene polymorphisms were not associated with the clinical pathological status of HCC and serum levels of liver-related clinical pathological markers. While no relationship between GSTM1 gene polymorphism and HCC susceptibility was found, individuals of age <56 years old with GSTT1 present genotype have a risk of 2.77-fold (95% CI: 1.09-7.09) for HCC compared to that with null variant, after adjustment for other confounders. CONCLUSIONS: GSTT1 and GSTM1 null genotypes do not associate with increased risk of HCC.

Parvalbumin-containing neurons mediate the feedforward inhibition of rat rubrospinal neurons.

The calcium-binding protein, parvalbumin and glutamic acid decarboxylase immunohistochemistry were used to locate candidate neurons mediating the inhibition of rat rubral neurons. A group of cells with small to medium-sized cell bodies that reacted positively to both were found in the red nucleus and its immediate vicinity. At the caudal nuclear level, these neurons gathered in the reticular formation, the pararubral area dorsolateral to the nucleus. As the nucleus expanded in size rostrally these neurons started to incorporate into the nucleus at about the anterior half of the middle nucleus and were all located within the rostral nucleus. Since these neurons were spatially segregated from the caudal nucleus we tested their connection by applying anterograde tracer to the pararubral area at the caudal red nuclear level. Labeled fibers with bouton-like swellings were found to enter the caudal nucleus and closely apposed rubrospinal neuronal cell bodies. These findings are consistent with our earlier observation that stimulating the pararubral area elicited a monosynaptic gamma-aminobutyric-acid(A) receptor-mediated inhibition on rubrospinal neurons in brainstem slices. In addition, the present study also shows that these inhibitory neurons remained unaltered in rats subjected to unilateral upper cervical rubrospinal tractotomy, suggesting that the reduction of pararubral stimulus-induced inhibition on rubrospinal neurons following spinal axonal injury resulted from causes other than the loss of these inhibitory neurons. In the rats, sensorimotor cortical fibers are known to reach the rostral red nucleus and the pararubral area but not the caudal nucleus. This prompted us to propose that neocortical inputs inhibit rubrospinal neurons through the activation of these PV-containing neurons. The proposed feedforward inhibitory circuit enables the cerebral cortex to disynaptically modulate the rubrospinal control over flexor motor execution.

In vivo protective effect of protocatechuic acid on tert-butyl hydroperoxide-induced rat hepatotoxicity.

Increasing evidence regarding free-radical generating agents and the inflammatory process suggests that accumulation of reactive oxygen species (ROS) can involve hepatotoxicity. Previously, we found that protocatechuic acid (PCA), a polyphenolic compound from Hibiscus sabdariffa L. possessing free radical-scavenging capacity, protected against oxidative damage induced by tert-butylhydroperoxide (t-BHP) in rat primary hepatocytes. In this study, first PCA was evaluated by its capacity of inhibiting xanthine oxidase (XO) and lipoxygenase (LO) activity in vitro, then it was used to induce hepatotoxicity to assess the antioxidant and anti-inflammatory bioactivity of PCA in vivo. Our investigation showed that pretreatment with PCA (50-100 mg/kg) by gavage for 5 days before a single dose of t-BHP (ip; 0.2 mmol/kg ) significantly lowered serum levels of the hepatic enzyme markers lactate dehydrogenase (LDH) and alanine (ALT) and aspartate (AST) aminotransferase, and reduced oxidative stress of the liver by evaluating malondialdehyde (MDA) and glutathione (GSH). Histopathological evaluation of the rat livers revealed that PCA reduced the incidence of liver lesions, including hepatocyte swelling, leukocyte infiltration, and necrosis induced by t-BHP. In addition, PCA inhibited t-BHP-induced tyrosine phosphorylation, an implication of the activation of a stress signal pathway, in the liver. These results indicate that PCA protects against t-BHP-induced hepatotoxicity by its antioxidant and anti-inflammatory characteristics accompanied by blocking of stress signal transduction.