Table 2.

Zinc supplementation studies in animal models of sepsis. LPS: lipopolysaccharide.

Animals	Sepsis Model	Intervention/Zn-Supply	Results (Zinc Group vs. Control Group)	Reference
Male mice (C57BL/6)	Intraperitoneal (i. p.) fecal slurry injection; sacrifice of mice at 24 h to conduct assays or observed 72 h for survival study	Zinc group: Injection of 10 mg/kg BW zinc gluconate every 24 h for 3 days prior to induction of sepsis, injection continued every 24 h after induction of peritonitis (corresponding to 1.4 mg/kg BW Zn2+ per day) Control group: Injection of equal volume of saline at the same time points as for the zinc group	• Significantly improved survival following sepsis at 72 h after induction • Significantly lower myeloperoxidase activity in lung tissue (at 24 h) • Significantly lower bacterial burden in blood and spleen (at 24 h) • Significantly lower serum keratinocyte chemoattractant concentration (at 24 h) • No significant difference between serum concentration of IL6, IL-1β, IL-10	[84]
Male and female mice (C57BL/6)	Cecal ligation and puncture; sacrifice of mice at 24 h	Zinc group: High-zinc diet (180 mg/kg) for 7 days prior to induction of sepsis Control group: Zinc-adequate diet (30 mg/kg) for 7 days prior to induction of sepsis	• Significantly lower IL-6 mRNA expression in hepatocytes • Significantly lower TNF-α mRNA expression in hepatic leukocytes • Significantly lower S100A9 mRNA expression in white blood cells • Significantly lower serum concentrations of TNF-α, S100A8 and S100A9 • Significantly lower serum concentration of plasma alanine aminotransferase • Significantly lower bacterial burden in blood and spleen	[50]
Male and female juvenile mice (C57BL/6)	I. p. cecal-slurry injection and measurement of blood samples at 6 h and 12 h; mice were sacrificed at 6 h or 12 h or observed for 72 h for survival study	Zinc group: Injection of 10 mg/kg BW zinc gluconate once a day for 3 days prior to induction of sepsis (corresponding to 1.4 mg/kg BW Zn2+ per day) Control group: Injection of equal volume of saline for 3 days prior to induction of sepsis	• Significantly improved survival of following sepsis at 72 h after induction • Significantly lower myeloperoxidase activity in lung tissue (at 12 h) • Significantly lower bacterial burden in peritoneal fluid (at 12 h) • Significantly lower serum concentrations of IL-2 (at 6 h, 12 h), IL-6 (at 6 h, 12 h), IL-1β (at 6 h), and keratinocyte-derived chemokines (at 12 h)	[83]
Female farm pigs (Deutsche Landrasse)	Intravenous infusion of LPS and measurement of the parameters for a duration of 300 min after infusion of LPS; pigs were sacrificed at 500 min of total registration time	Zinc group: Infusion of 25 mg/kg BW zinc-bis-(dl-hydrogenaspartate) 24 h prior to infusion of LPS (corresponding to 5 mg/kg BW Zn2+ per day) Control group: Infusion of saline 24 h prior to infusion of LPS	• Increased arterial and venous oxygen pressure (reaching significance at 45 min or 210 min) • Increased arterial and venous oxygen saturation (reaching significance at 210 min) • Stable intrapulmonary shunt (instead of an increase in the control group) • Stable extravascular lung water (EVLW) (instead of an increase in the control group)	[85]
Female farm pigs (Deutsche Landrasse)	Intravenous infusion of LPS and measurement of parameters for a duration of 60 min after infusion of LPS; pigs were sacrificed at 60 min and organs removed for analysis	Zinc group: Infusion of 25 mg/kg BW zinc-bis-(dl-hydrogenaspartate) 2 h prior to infusion of LPS (corresponding to 5 mg/kg BW Zn2+ per day) Control group: Infusion of saline 2 h prior to infusion of LPS	• Decrease in arterial and venous oxygen pressure (reaching significance at 30 min) • Decrease in arterial and venous oxygen saturation(reaching significance at 30 min or 15 min) • Increase in intrapulmonary shunt (reaching significance at 30 min) • Increase in EVLW (reaching significance at 45 min) • Increase in mean hemoglobin (reaching significance at 30 min) • Increase in IL-6 and TNF-α plasma concentrations (reaching significance at 0 min or 45 min) • Significant higher weights of lungs, width of alveolar septae and rate of paracentral liver necrosis	[87]
Female farm pigs (Deutsche Landrasse)	Intravenous infusion of LPS and measurement of parameters for a duration of 1020 min, with infusion of zinc from 600 to 720 min; pigs were sacrificed at the end of the study period and a necropsy carried out	Zinc group: Infusion of LPS at 0 h, 5 h and 12 h, infusion of 25 mg/kg BW zinc-bis-(dl-hydrogenaspartate)(corresponding to 5 mg/kg BW Zn2+ per day) at 10 h during sepsis Control group: Infusion of LPS at 0 h, 5 h and 12 h, infusion of saline at 10 h during sepsis	• Trend to higher arterial and venous oxygen pressure • Trend to higher arterial and venous oxygen saturation • No significant differences in intrapulmonary shunt • No significant differences in EVLW • Different courses in IL-6 and TNF-α plasma concentrations, at the end almost similar levels	[86]