Home  About us  Contact
 

RC Rats (rc + rat)

Distribution by Scientific Domains
Life Sciences100%

Selected Abstracts

The effects of dietary flaxseed on the Fischer 344 rat.

CELL BIOCHEMISTRY AND FUNCTION, Issue 6 2005

Abstract The hepatotoxic effect of carbon tetrachloride (CCl4) administered by gavage at 0.25,ml CCl4 (1:1 in olive oil) per 100,g body weight was examined 24,h later in regular chow fed (RC) and 10% flax chow fed (FC) male and female Fischer 344 rats. CCl4 -treated RC rats were subdued, lethargic and unkempt. CCl4 -treated FC rats were much less affected. CCl4 treatment resulted in loss of weight in RC and FC rats. In males, the weight loss was 6.7% body mass in RC rats compared to 5.6% body mass in FC rats. In females, the weight loss was 7.5% body mass in both RC and FC rats. While CCl4 treatment increased the level of the liver injury marker plasma alanine aminotransferase (ALT) in RC rats, this CCl4 effect was significantly attenuated in FC rats. In male rats, the ALT increase was 435-fold in RC rats and 119-fold in FC rats, over that of their respective controls. In female rats, the ALT increase was 454-fold in RC rats and 381-fold in FC rats, over that of their respective controls. These results provide evidence that flax consumption protects the liver against injury and that the extent of the protection is sex dependent. CCl4 had no effect on the plasma level of ,-glutamyltranspeptidase (,GT) in RC and FC rats supporting the contention that plasma ,GT is not a useful marker for acute liver injury which is seen in this model. The activity of ,GT was increased in the livers of FC rats compared to RC rats: 2.7-fold in males and 1.5-fold in females. In RC rats, the activity of liver ,GT was decreased by CCl4 treatment: 70% in the male and 25% in the female. However, this CCl4 effect was reversed or abolished by flax consumption. Compared to RC rats: in male FC rats, CCl4 actually increased the activity of liver ,GT 1.28-fold; while in female FC rats, the depressing effect of CCl4 treatment was abolished. The flax-induced preservation of ,GT in the liver in response to injury may be involved in the observed hepatoprotection through generation of GSH. In RC male rats, CCl4 treatment effected a 25% reduction in plasma glucose levels. There was no decrease in CCl4 -treated FC male rats. In female rats, CCl4 treatment effected a 21% decrease in plasma glucose levels in both RC and FC rats. In conclusion, multiple parameters for acute CCl4 -induced injury were attenuated in the FC compared to the RC rat. That flaxseed consumption conferred greater protection against liver injury in the male than in the female suggests an involvement of the estrogenic lignan component of flaxseed. We discuss the possibility that this hepatoprotection is through a flax lignan-induced increase in reduced glutathione related to a flax effect on the activity of liver ,GT in the resting state and the maintenance of its activity in response to injury. Copyright © 2005 John Wiley & Sons, Ltd. [source]

Synergistic neuroprotective effect via simian lentiviral vector-mediated simultaneous gene transfer of human pigment epithelium-derived factor and human fibroblast growth factor-2 in rodent models of retinitis pigmentosa

THE JOURNAL OF GENE MEDICINE, Issue 12 2008
Masanori Miyazaki
Abstract Background We previously demonstrated that a new lentiviral vector derived from nonpathogenic simian immunodeficiency virus (SIVagm) was efficient and safe for long-lasting retinal gene transfer, and that it provided the significant therapeutic effect of expressing human pigment epithelium-derived factor (hPEDF) in Royal College of Surgeons (RCS) rats. In the present study, to obtain a more pronounced outcome, we assessed the potential synergistic effect of the simultaneous gene transfer of hPEDF and human fibroblast growth factor-2 (hFGF-2) by improved third-generation SIV on RCS rats and retinal degeneration slow (rds) mice, because the former targets the primary neurons, including photoreceptor cells (PCs), whereas the latter is effective for targeting secondary neural cells, including Muller cells. Methods Vector solution (SIV-hPEDF, SIV-hFGF-2, a 1 : 1 mixture of SIV-hPEDF and SIV-hFGF-2, or SIV-enhanced green fluorescent protein) was injected into the peripheral subretinal space of 3-week-old RCS rats or rds mice. Histopathological and electroretinographic assessments were made at several points after gene transfer. Results Administration of SIV-hPEDF or SIV-hFGF-2 significantly delayed the histological PC degeneration and electrical deficit in RCS rats, and these delays were synergistically and significantly pronounced by SIV-hPEDF + SIV-hFGF-2 (1 : 1 mixture). In rds mice, functional therapeutic effects were observed even by SIV-PEDF, or SIV-FGF-2 alone and, moreover, both SIV-PEDF and SIV-FGF-2 showed higher therapeutic effects. Conclusions These synergistic rescues of retinitis pigmentosa (RP) model animals are the ,proof concept' that the ,dual' expression of hPEDF and hFGF-2 dramatically improved therapeutic efficacy by keeping lower titers. This strategy may contribute to safer and more effective gene therapy for RP. Copyright © 2008 John Wiley & Sons, Ltd. [source]