Lesions and Distribution of Viral Antigen in the Brain of Hamsters Infected With Equine Herpesvirus (EHV)-9, EHV-1 Strain Ab4p, and Zebra-Borne EHV-1.

Encephalitis in hamsters, which was induced by equine herpesvirus (EHV)-9, EHV-1 strain Ab4p, and zebra-borne EHV-1, was investigated and compared to assess viral kinetics and identify the progression and severity of neuropathological findings. Hamsters were inoculated with EHV-9, EHV-1 strain Ab4p, and zebra-borne EHV-1 via the nasal route and euthanized at 24, 48, 72, 96, 120, 144, and 168 hours postinoculation (HPI). The inoculated hamsters had mild to severe neurological signs at 60 to 72, 96, and 120 HPI, and the mortality rate was 75%, 0%, and 0% for animals inoculated with EHV-9, EHV-1 strain Ab4p, and zebra-borne EHV-1 viruses, respectively. Inoculated hamsters had varying degrees of rhinitis and lymphoplasmacytic meningoencephalitis, as well as differences in the severity and distribution of cerebral lesions. Furthermore, the cellular distribution of viral antigen depended on the inoculated virus. Neuronal necrosis was widely detected in animals inoculated with EHV-9, while marked perivascular cuffs of infiltrating inflammatory cells and gliosis were detected in animals inoculated with EHV-1 strain Ab4p and zebra-borne EHV-1. In the present study, 3 viruses belonging to the herpesvirus family induced encephalitis after initial propagation in the nasal cavity. These viruses might travel to the brain via the olfactory pathway and/or trigeminal nerve, showing different distributions and severities of neuropathological changes.

Effects of food restriction on the expression of genes related to acetaminophen-induced liver toxicity in rats.

It is well known that fasting substantially affects the metabolism of drugs and chemicals. Food restriction also affects drug kinetics, such as absorption, metabolism, and excretion, and therefore, it can potentially modulate the onset of chemical toxicity or drug-induced adverse reactions. In the present study, the expression of drug-metabolizing enzyme genes and total glutathione content in the liver, which are related to toxicity induced by overdose of the hepatotoxic drug acetaminophen (N-acetyl-p-aminophenol; APAP), were examined in rats reared under different feeding conditions: ad libitum feeding, 16-h fasting, and food restriction (fed 70% of the average intake of ad libitum feeding for 10 days) conditions. The rats under food restriction conditions as well as fasted rats showed significantly higher expression of Cyp2e1, the gene encoding the enzyme that metabolizes APAP to its toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). They also had lower levels of liver total glutathione, which detoxifies NAPQI. In contrast, the gene expression of UDP-glucuronosyltransferase 1A6 (Ugt1a6), sulfotransferase 1A1 (Sult1a1), and glutathione S-transferase M1 (Gstm1) was not affected by food restriction or fasting. When APAP was administered (800 mg/kg), histopathological changes were not observed in rats fed ad libitum, while hepatocellular necrosis was observed in most of the rats treated with APAP after fasting or food restriction. Taken together, these results suggest that not only fasting but also food restriction exacerbate APAP-induced acute liver injury, probably by the induction of CYP2E1 and the reduction of liver glutathione contents, in rodents.

Brazilian green propolis suppresses acetaminophen-induced hepatocellular necrosis by modulating inflammation-related factors in rats.

Propolis is a resin-like material produced by honey bees from bud exudates and sap of plants and their own secretions. An ethanol extract of Brazilian green propolis (EEBGP) contains prenylated phenylpropanoids and flavonoids and has antioxidative and anti-inflammatory effects. Acetaminophen (N-acetyl-p-aminophenol; APAP) is a typical hepatotoxic drug, and APAP-treated rats are widely used as a model of drug-induced liver injury. Oxidative stress and inflammatory reactions cause APAP-induced hepatocellular necrosis and are also related to expansion of the lesion. In the present study, we investigated the preventive effects of EEBGP on APAP-induced hepatocellular necrosis in rats and the protective mechanism including the expression of antioxidative enzyme genes and inflammation-related genes. A histological analysis revealed that administration 0.3% EEBGP in the diet for seven days reduced centrilobular hepatocellular necrosis with inflammatory cell infiltration induced by oral administration of APAP (800 mg/kg) and significantly reduced the area of necrosis. EEBGP administration did not significantly change the mRNA expression levels of antioxidant enzyme genes in the liver of APAP-treated rats but decreased the mRNA expression of cytokines including Il10 and Il1b, with a significant difference in Il10 expression. In addition, the decrease in the mRNA levels of the Il1b and Il10 genes significantly correlated with the decrease in the percentage of hepatocellular necrosis. These findings suggest that EEBGP could suppress APAP-induced hepatocellular necrosis by modulating cytokine expression.

Inhibitory effect of propolis on the development of AA amyloidosis.

In the several types of amyloidoses, participation of oxidative stresses in the pathogenesis and the effect of antioxidants on amyloidosis have been reported. Meanwhile, the relationship between oxidative stresses and pathogenesis of amyloid A (AA) amyloidosis is still unclear. In this study, we used an antioxidant, Brazilian propolis, to investigate the inhibitory effects on AA amyloidosis. The results showed that AA deposition was inhibited by administration of propolis. Increased expression of antioxidant markers was detected in molecular biological examinations of mice treated with propolis. Although serum amyloid A (SAA) levels were strongly correlated with the immunoreactive area of AA deposits in the control group, the correlation was weaker in the propolis-treated groups. In addition, there were no changes in SAA levels between the control group and the propolis-treated groups. The results indicate that propolis, an antioxidant, may induce inhibitory effects against AA amyloidosis.