Key findings
These researchers have shown flax-induced increases in the activity of liver gGT may be hepatobeneficial. The objectives of the present study were to test this hypothesis. The results have shown that CCl4 treatment leads to a significant decrease in blood glucose levels, which approximates the degree of toxic liver injury. Flaxseed showed liver protection by reducing a CCl4-induced decrease in liver GSH. The study showed flaxseed consumption can protect the liver from acute injury and that mechanistically this protection may be expressed through alterations in the status of the liver enzyme gGT with preservation of GSH levels.
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 g-glutamyltranspeptidase (gGT) in RC and FC rats supporting the contention that plasma gGT is not a useful marker for acute liver injury which is seen in this model. The activity of gGT 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 gGT 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 gGT 1.28-fold; while in female FC rats, the depressing effect of CCl4 treatment was abolished. The flax-induced preservation of gGT 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 gGT in the resting state and the maintenance of its activity in response to injury.