Historical control data from prenatal developmental toxicity studies in rats have been used to evaluate whether toxicology outcomes were induced by exposure to a chemical or were within the range of spontaneous variation. These data are also important for monitoring animal characteristics. As a follow-up to historical control data from 1998 to 2010, this study analyzed control data from prenatal developmental studies performed in rats from 2011 to 2015. Data were collected from studies performed by 24 Japanese laboratories, including 15 pharmaceutical and chemical companies and nine contract research organizations, in Sprague-Dawley and two-sub-strains of Wistar Hannover rats. The data included maternal reproductive findings at terminal cesarean section and fetal findings, including incidences of spontaneous external, visceral, and skeletal anomalies. No noticeable differences in maternal reproductive data were observed among laboratories. The inter-laboratory variations in the incidences of fetal anomalies seemed to be due to differences in the selection of observation parameters, observation criteria, and classification of the findings, as well as to differences in terminology of fetal alterations. These historical control data may be helpful for adequate interpretation of experimental results and for evaluating the reproductive and developmental toxicities of various chemicals.
Hydroxytyrosol (HT) is a simple phenol compound present in olive oil. In a previous in vitro study, we showed that HT downregulated lipopolysaccharide-mediated expression of inducible nitric oxide synthase, cyclooxygenase-2 (COX-2), tumor necrosis factor alpha, and interleukin-1β, resulting in reduced nitric oxide and prostaglandin E 2 production. In the present study, we aimed to determine whether HT suppresses COX-2-induced inflammation in a carrageenan-induced rat paw edema model. Additionally, we compared its activity with those of the selective COX-2 inhibitor, celecoxib for a comparative control, and a representative nonsteroidal anti-inflammatory drug (NSAID), indomethacin for a positive control. HT, celecoxib, and indomethacin significantly suppressed swelling in carrageenan-injected rat paws. Although HT was less effective than celecoxib and indomethacin, it had a delayed onset of action. Moreover, we evaluated whether HT aggravates gastric damage, which is a typical adverse effect associated with NSAIDs and COX-2 inhibitors under low dose aspirin (LDA) treatment, in an aspirin-induced gastric damage rat model. Unlike celecoxib and indomethacin, HT did not cause gastric damage when co-administered with aspirin. Our results indicate that HT exerts a delayed but sustained anti-inflammatory effect against COX-2-mediated inflammation. Finally, the combination of short-acting conventional anti-inflammatory drugs and long-acting HT can be considered a new, safe, and effective anti-inflammatory treatment modality even when continuously administered for a long period under LDA treatment.
Avian amyloid A (AA) amyloidosis is commonly observed in adult birds with chronic
inflammation, such as that caused by bacterial infection. We previously described
vaccine-associated AA amyloidosis in juvenile chickens. In this study, the prevalence of
amyloid deposition was measured in mature healthy chickens that survived a previous
outbreak of avian AA amyloidosis while they were juveniles. Herein, we analyzed the
amyloid deposition in mature chickens and compared the prevalence of amyloid deposition
with juvenile chickens obtained in our previous study (Murakami et al.,
2013). We found that: 1) amyloid deposition in the liver was absent in mature chickens,
while juvenile chickens had a rate of 24%; 2) amyloid deposition in the spleen was
observed in 36% of juvenile chickens and in 40% of mature chickens; 3) amyloid deposition
in the pectoral muscle of mature chickens (43.75%) was approximately half that of juvenile
chickens (88%). These results suggest that additional amyloid deposition in chickens
previously exposed to AA amyloidosis may not worsen with age. Further, amyloid deposition
in chickens may tend to regress when causative factors, such as vaccinations and/or
chronic inflammation, are absent.
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