Cardioprotective potential of tectochrysin against vanadium induced heart damage via regulating NLRP3, JAK1/STAT3 and NF-κB pathway

Abstract

Background

Vanadium (VAN) is a significant trace element, but its higher exposure is reported to cause severe organ toxicity. Tectochrysin (TEC) is a naturally derived flavonoid which demonstrates a wide range of pharmacological properties.

Aim

The current study was planned to assess the cardioprotective potential of TEC against VAN induced cardiotoxicity in rats via regulating biochemical, and histological profile.

Research plan

Thirty-six male Sprague Dawley rats were apportioned into four groups including the control, VAN (1.5 mg/kg) treated, VAN (1.5 mg/kg) + TEC (2.5 mg/kg) administrated as well as TEC (2.5 mg/kg) alone supplemented group. The doses were administrated for 28 days through oral gavage. The biochemical and histological parameters were evaluated by using qRT-PCR, ELISA, biochemical assays, histological as well as molecular simulation techniques.

Findings

VAN intoxication reduced the activities of catalase (CAT) (84.25 %), glutathione peroxidase (GPx) (65.28 %), glutathione reductase (GSR) (78.52 %), heme oxygenase-1 (HO-1) (81.81 %), superoxide dismutase (SOD) (83.71 %) and glutathione (GSH) (76.86 %) contents while upregulating the levels of reactive oxygen species (ROS) (87.26 %) and malondialdehyde (MDA) (91.32 %). Moreover, VAN administration increased the gene expressions of nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) (91.47 %), monocyte chemoattractant protein-1 (MCP-1) (92.51 %), interleukin-6 (IL-6) (83.63 %), tumor necrosis factor-alpha (TNF-α) (89.43 %), janus kinase 1 (JAK1) (95.55 %), signal transducer and activator of transcription 3 (STAT3) (91.25 %), nuclear factor-kappa B (NF-κB) (81.31 %), interleukin-18 (IL-18) (93.27 %), interleukin-1 beta (IL-1β) (85.79 %) and cyclooxygenase-2 (COX-2) (82.12 %). The levels of CK-MB (89.43 %), BNP (91.73 %), NT-proBNP (93.64 %), CPK (87.56 %), LDH (92.62 %), troponin I (94.25 %), troponin T (97.53 %) and CRP (88.45 %) were increased following the VAN intoxication. Besides, VAN exposure upregulated the levels of Caspase-9 (89.52 %), Bax (95.52 %) and Caspase-3 (92.52 %) while reducing the levels of Bcl-2 (75.66 %). The structural integrity of cardiac tissues was extensively disrupted following VAN-induced intoxication. However, TEC treatment remarkably ameliorated cardiotoxicity via regulating abovementioned dysregulations induced by VAN exposure. At the end, molecular docking (MD) analysis was accomplished to confirm the potential protective effect of TEC against VAN prompted cardiac dysfunction. It was detected that TEC can strongly bind with the active site of JAK1, NF-kB and STAT3 which also confirm its cardioprotective effect against VAN provoked cardiac dysfunction.

Conclusion

VAN intoxication instigated cardiac impairments which is evident by dysregulations in biochemical as well as histological profile of cardiac tissues. Nonetheless, TEC treatment remarkably protected the cardiac tissues via regulating oxidative stress, inflammation and apoptosis. TEC could be employed as cardioprotective agent against VAN induced cardiotoxicity.