Effects of mild zinc deficiency, plus or minus an acute-phase response, on galactosamine-induced hepatitis in rats.

Zn deficiency is hypothesized to produce poor resistance to injury involving oxidative stress. This could occur by impairing Zn antioxidant function(s) or by indirectly limiting adaptive protective mechanisms such as a rise in acute-phase proteins. The present study examined rats fed diets adequate or moderately low in Zn (4 or 25 micrograms/g diet) for 9 d. The lower intake produced a mild Zn deficiency based on body weight, plasma Zn and plasma alkaline phosphatase (EC 3.1.3.1) activity. Galactosamine injection, an oxidative stress, produced much more liver injury in the mildly Zn-deficient rats. However, injury was strongly inhibited in rats from each dietary group by an acute-phase response due to turpentine-induced leg inflammation. Mild Zn deficiency did not prevent a rise in levels of the acute-phase protein caeruloplasmin (EC 1.16.3.1), but did limit the usual inflammation-induced rise in hepatic levels of metallothionein, a Zn protein with possible antioxidant function. In conclusion, high degrees of galactosamine-induced hepatitis were associated with mild Zn deficiency, but the liver injury was blocked by prior stimulation of an acute-phase response, regardless of Zn status.