The regulatory effects of pomiferin dietary on nickel-induced hepatic injury in Sprague–Dawley rats; action mechanisms and signaling pathways

Abstract

The new technological applications of nickel (Ni) raise concerns over its harmful effects on the environment and human health. Pomiferin isolated from Osage orange is evaluated in in vitro and in vivo laboratory bioassays. This study focused the effects of pomiferin on Ni-caused hepatic injury and its underlying mechanisms. With this aim, Sprague–Dawley rats received 10 mg/kg nickel chloride (NiCl₂) for 7 d by intraperitoneal injections. Pomiferin was given orally once a day at different doses (75, 150, and 300 mg/kg) for 20 d after exposure to NiCl₂. Animals were anesthetized and livers were carefully collected to evaluate oxidative stress, inflammation, vascular injury, and hepatic function. Also, immunofluorescence analysis of apoptosis and DNA damage was performed on rat hepatic tissues. NiCl₂ increased MDA production while reducing SOD, CAT, and GPx activity. NiCl₂ induced the production of inflammatory cytokines and also platelet activation in hepatic tissue. Moreover, there were significant increases in AST, ALT, and LDH levels. NiCl₂ also caused significant pathological changes in hepatic. Additionally, it remarkably induced up-regulations of apoptotic marker and 8-OHdG expressions by immunofluorescence labeling in liver cells. Whereas, pomiferin significantly attenuated lipid peroxidation and increased antioxidant defense system in liver. Also, the use of pomiferin prevented deregulated inflammatory process by signaling pathways nuclear factor kappa B (NFκB)/COX-2/TNF-α/IL-1β/IL-6. In addition, pomiferin diminished histopathologic evidence of hepatic toxicity and significantly lower expressions of caspase 3 and 8-OHdG were observed in liver cells. Pomiferin seems to counteract the deleterious effects of NiCl₂ on hepatic tissue through different cellular and signaling mechanisms.

HIGHLIGHTS

• NiCl₂ induced the production of inflammatory cytokines and also platelet activation in hepatic tissue.

• NiCl₂ increased MDA production while reducing SOD, CAT, and GPx activity.

• NiCl₂ induced the production of inflammatory cytokines and also platelet activation in hepatic tissue.

• NiCl₂ caused significant pathological changes in the liver and also up-regulation of apoptotic marker and 8-OHdG expressions by immunofluorescence staining.

• Pomiferin attenuated lipid peroxidation and increased antioxidant defense system in liver.

• The use of pomiferin prevented deregulated inflammatory process by signaling pathways nuclear factor kappa B (NFκB)/COX-2/TNF-α/IL-1β/IL-6.

• Pomiferin diminished histopathologic evidence of hepatic toxicity and significantly lower expressions of caspase 3 and 8-OHdG were observed in liver cells.

• Pomiferin seems to counteract the deleterious effects of NiCl₂ on hepatic tissue through different cellular and signaling mechanisms and thus can be used as a therapeutic practice against metal toxicity.

Keywords:

• Apoptosis
• DNA damage
• nickel toxicity
• platelet aggregation
• pomiferin

Author contributions statement

Gulsah Yildiz Deniz: Methodology, Data curation, Formal analysis, Visualization, and Writing – original draft. Fatime Geyikoglu: Methodology, Formal analysis, and Writing – review and editing. Serdar Altun: Validation, Writing – review and editing.

Disclosure statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article.

Data availability

Data will be made available on request.