Comparative hepatoprotective efficacy of spirulina polysaccharides and crude spirulina against metalaxyl-m toxicity via modulation of oxidative stress and Nrf2/NF-κB gene expression

The liver stands as the central metabolic hub of the body, acting as the primary frontline defense against systemic toxins and xenobiotics. However, this relentless detoxification role renders it uniquely vulnerable to the escalating threat of modern agrochemicals. Among these, metalaxyl-m, a widely utilized chiral pesticide, poses a significant risk, as the global shift toward sophisticated chemical synthesis continues to increase the prevalence of such bioactive compounds. This study was designed to investigate the hepatotoxic mechanisms of metalaxyl-m and explore the potential of spirulina platensis, along with its bioactive polysaccharides, in neutralizing this damage. Our findings revealed that metalaxyl-m exposure triggered severe hepatotoxicity by disrupting the Nrf2/HO-1 signaling pathway, leading to a collapse in the antioxidant defense system (GSH, CAT, SOD), profound oxidative stress (elevated MDA), and a sharp rise in liver enzymes (ALT, AST). At the molecular level, toxicity was driven by the upregulation of inflammatory and apoptotic markers, including TNF-α, TLR4 and NF-kB. Conversely, the administration of spirulina and its isolated polysaccharides effectively counteracted these pathological shifts. Notably, spirulina polysaccharides effectively preserved hepatocyte integrity and markedly upregulated tissue immunohistochemical expression of SIRT1. These findings highlight their protective potential as a natural candidate for mitigating pesticide-induced hepatotoxicity.