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Article

Metallothionein in Mice Reduces Intestinal Zinc Loss during Acute Endotoxin Inflammation, but Not during Starvation or Dietary Zinc Restriction

Division of Clinical Biochemistry, Institute of Medical and Veterinary Science, Adelaide, SA 5000 Australia

¹To whom correspondence should be addressed.

Normal metallothionein [(MT)+/+] and MT-null (MT-/-) mice were used to examine the influence of MT on Zn retention and the metabolic consequences of 2 d food deprivation, with and without inflammation induced by intraperitoneal injection of bacterial endotoxin lipopolysaccharide (LPS). LPS reduced fecal Zn concentration in MT+/+ mice from 5.9 ± 0.2 µmol/g on d 1 to 2.2 ± 0.2 µmol/g on d 2, but not in MT-/- mice, 5.9 ± 0.2 and 5.7 ± 0.5 µmol/g, respectively. MT+/+ mice fed an 8 mg Zn/kg diet and injected with LPS excreted 40% less Zn over 2 d than their MT-/- counterparts. Starvation for 2 d did not lower fecal Zn concentration in either genotype, although in MT+/+ mice, urinary Zn excretion was reduced from 12.7 ± 1.3 nmol on d 1 to 5.9 ± 1.8 nmol on d 2 and plasma Zn concentration was lowered to 9.8 ± 0.4 µmol/L. Zn was not reduced in urine or plasma of MT-/- mice, with respective values of 10.8 ± 2.0 nmol on d 1, 9.3 ± 2.9 nmol on d 2 and 13.0 ± 1.0 µmol/L. LPS injection resulted in much higher total liver Zn (677 ± 27 nmol) and MT (106 ± 2 nmol Cd bound/g) than starvation (Zn = 405 ± 21, MT = 9 ± 3) in MT+/+ mice after 2 d, but did not further reduce urinary Zn. LPS-injected MT-/- mice had no rise in liver Zn or fall in plasma and urine Zn. MT-/- mice fed a Zn-deficient (0.8 mg Zn/kg) diet lost 10% of body weight over 25 d compared with no loss in MT+/+ mice. Despite this, MT-/- mice excreted no more Zn via the gut than did MT+/+ mice. In summary, MT inhibits intestinal Zn loss when highly expressed. When uninduced, typically during Zn deficiency, MT appears to conserve Zn and body mass by reducing only urinary and other nonintestinal Zn losses.

KEY WORDS: • mice • metallothionein • zinc • endotoxin

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