Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) · 2025
Therapeutic potential of spinacetin against cadmium-exacerbated hepatic ischemia/reperfusion injury via regulating AMPK/SIRT1/PGC-1α and NF-κB pathway.
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Bibi Aqsa, Zhang Hong-Xing, Hayat Muhammad Faisal, Alzahrani Khalid J, Alsharif Khalaf F, Alzahrani Fuad M
Аннотация
BACKGROUND: Cadmium (Cd) is a potent environmental toxicant that affect different body organs including the liver. Spinacetin (SPI) is a plant-derived polyphenolic compound with diverse biological activities.
OBJECTIVE: The current investigation assessed the palliative potential of SPI against Cd-exacerbated hepatic ischemic/reperfusion (I/R) injury in rats.
METHODOLOGY: Forty male albino rats were apportioned into five groups including the sham, I/R induced, I/R + Cd (5 mg/kg), I/R + Cd (5 mg/kg) + SPI (50 mg/kg), and I/R + SPI (50 mg/kg) treated group. Gene expressions were quantified using qRT PCR. Biochemical assessments were performed using ELISA technique and standard assays. Results were cross validated through molecular simulation and molecular docking analysis.
FINDINGS: It was revealed that Cd intoxication in I/R group downregulated the gene expression of silent information regulator sirtuin-1 (SIRT1), adenosine monophosphate-activated protein kinase (AMPK), mitochondrial transcription factor-A (TFAM), peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC-1α), and Estrogen-Related Receptor Alpha (ERRα) while upregulating the mRNA expressions of COX-2, TNF-α, IL-6, IL-1β, and NF-κB. Enzymatic potential of glutathione reductase (GSR), superoxide dismutase (SOD), glutathione reductase (GSR), catalase (CAT), heme-oxygenase-1 (HO-1), glutathione peroxidase (GPx), and concentration of glutathione (GSH) were suppressed while the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were upregulated following the Cd intoxication in I/R induced group. Cd intoxication in IR group escalated the levels of ALT, AST, ALP, and GGT while reducing the intensity of albumin and total protein. Moreover, I/R-induced and IR + Cd group showed upregulation in Bax, Caspase-3 and Caspase-9 while reducing the levels of Bcl-2. Severe histological impairments were observed in I/R as well as I/R + Cd treated group. Nonetheless, SPI therapy showed significant protection of hepatic tissues against I/R and I/R + Cd intoxication via regulating mitochondrial biogenesis, oxidative stress, inflammation, apoptosis and histological impairments.
CONCLUSION: Cd intoxication escalates the hepatic ischemic injury via upregulating oxidative injury, inflammation and other key regulatory pathways. Spinacetin reversed I/R-mediated hepatic damage, demonstrating its potential hepatoprotective efficacy.
OBJECTIVE: The current investigation assessed the palliative potential of SPI against Cd-exacerbated hepatic ischemic/reperfusion (I/R) injury in rats.
METHODOLOGY: Forty male albino rats were apportioned into five groups including the sham, I/R induced, I/R + Cd (5 mg/kg), I/R + Cd (5 mg/kg) + SPI (50 mg/kg), and I/R + SPI (50 mg/kg) treated group. Gene expressions were quantified using qRT PCR. Biochemical assessments were performed using ELISA technique and standard assays. Results were cross validated through molecular simulation and molecular docking analysis.
FINDINGS: It was revealed that Cd intoxication in I/R group downregulated the gene expression of silent information regulator sirtuin-1 (SIRT1), adenosine monophosphate-activated protein kinase (AMPK), mitochondrial transcription factor-A (TFAM), peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC-1α), and Estrogen-Related Receptor Alpha (ERRα) while upregulating the mRNA expressions of COX-2, TNF-α, IL-6, IL-1β, and NF-κB. Enzymatic potential of glutathione reductase (GSR), superoxide dismutase (SOD), glutathione reductase (GSR), catalase (CAT), heme-oxygenase-1 (HO-1), glutathione peroxidase (GPx), and concentration of glutathione (GSH) were suppressed while the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were upregulated following the Cd intoxication in I/R induced group. Cd intoxication in IR group escalated the levels of ALT, AST, ALP, and GGT while reducing the intensity of albumin and total protein. Moreover, I/R-induced and IR + Cd group showed upregulation in Bax, Caspase-3 and Caspase-9 while reducing the levels of Bcl-2. Severe histological impairments were observed in I/R as well as I/R + Cd treated group. Nonetheless, SPI therapy showed significant protection of hepatic tissues against I/R and I/R + Cd intoxication via regulating mitochondrial biogenesis, oxidative stress, inflammation, apoptosis and histological impairments.
CONCLUSION: Cd intoxication escalates the hepatic ischemic injury via upregulating oxidative injury, inflammation and other key regulatory pathways. Spinacetin reversed I/R-mediated hepatic damage, demonstrating its potential hepatoprotective efficacy.