Effects of mild zinc deficiency, plus or minus acute phase response, on CCl4 hepatotoxicity

Low zinc (Zn) intake could be expected to compromise resistance to oxidative stress, even when accompanied by a normally protective acute phase response pretreatment. Mildly Zn deficient rats showed very high degrees of CCl4-induced hepatic cell membrane injury as assessed by serum sorbitol dehydrogenase activities. Rats pair-fed adequate Zn also showed above normal degrees of injury, but much less than rats fed low Zn. An acute phase response, elicited by leg inflammation, strongly protected rats consuming adequate Zn, either ad libitum or pair-fed, against the CCl4-induced rise in sorbitol dehydrogenase. However, the effect was partially absent in rats fed low Zn. Zinc intake had no effect on CCl4-produced microsomal injury, assessed by glucose-6-phosphatase activities. Rats fed low Zn showed normal hepatic levels of metallothionein, a Zn protein with proposed antioxidant functions, but did not show the rise in metallothionein levels normally associated with acute phase response. In summary, mild Zn deficiency caused poor resistance to CCl4-induced plasma membrane injury and partially negated acute phase response protective effects. Metallothionein was not involved in the former effect, but may have contributed to the latter.