Zinc modulates nickel-induced oxidative stress in the liver of murine model

Background. Chronic nickel exposure is increasingly recognized for its potential to disrupt liver function and metabolic homeostasis. Zinc, an essential trace element, plays key roles in enzymatic activity, metal binding, and antioxidant defence, with evidence suggesting competitive interactions with nickel. Investigating their combined effects may clarify the interactions between toxic and protective metals in the liver and provide insight into potential interventions.

Aim. This study evaluated the impact of zinc on oxidative stress biomarkers in the livers of nickel-exposed mice.

Methods. Animals were divided into control, nickel-exposed, zinc-exposed, and zinc-plus-nickel exposure groups. The oxidative status of the liver was assessed by measuring the levels of reduced glutathione (GSH), malondialdehyde (MDA) and metallothionein (MT) expression.

Results. A single NiCl₂ injection decreased hepatic GSH by 28%, while zinc alone caused no significant change. Zinc pre-treatment (20 min prior to NiCl₂) led to a further 40% decrease. After 14 days, GSH levels were comparable across groups and remained at control level. MDA increased by 282% after a single NiCl₂ dose and by 87% after repeated exposure. Zinc alone reduced MDA by 20% after a single dose but had no effect after prolonged exposure. Pre-treatment with zinc attenuated Ni-induced MDA elevation by 146% after a single exposure and by 50% after repeated exposure. MT expression increased by 35% after a single NiCl₂ injection and by 57% after 14 days. Zinc alone elevated MT by 20% (single dose) and 48% (14 days). Combined exposure resulted in greater MT induction, reaching 41% after a single treatment and 70% after repeated exposure.

Conclusion. These findings indicate that nickel induces hepatic oxidative stress, while zinc modulates this response in a time-dependent manner. The protective effect of zinc against lipid peroxidation may be linked to its ability to induce metallothionein expression.