Research Of Repairment Mechanism Of Curcumin On Lead-induced Rats Hepatotoxicity

Lead, a common environmental contaminants, is widely distributed in the environment, it can be entered and distributed in the body organs through a variety of routes,therefore it can lead to the occurrence of various liver diseases, even low levels of lead exposure could cause multiple organ damage. The liver was the target organ of the toxic effects of lead, which could lead to the occurrence of various liver diseases. now that the main mechanism of lead poisoning was its oxidative stress, but the mechanism of hepatitis injury caused by lead is not clear. Recent studies in vitro have shown that lead could phosphorylate epidermal growth factor receptor (EGFR) and its activity was increased, at the same time, it promoted downstream extracellular protein kinase (ERK1), cytosolic phospholipase (CPLA2), cyclooxygenase (COX-2) activity, arachidonic acid (AA) was dissociated from the cell membrane under the action of CPLA2, then promoted the increasement in prostaglandin E2 (PGE2) levels, inflammation was induced to cells damage, but AA metabolites PGE2, 20-hydroxyl-eicosanoic arachidonic acid (20-HETE), epoxidized eicosatrienoic acid (EETS) were involved in the inflammation of the liver caused by lead, related studies have not been reported. Curcumin is a kind of natural flavonoid antioxidants, has a variety of.pharmacologically active complex, anti-inflammatory, which makes it possible to reduce the heavy metal damage, research about if curcumin antagonistic organ toxicity of lead has been excuted, But whether curcumin mitigate lead-induced liver inflammation by inhibiting EGFR-AA pathway was unclear, and wethere curcumin could preliminarily repair lead-induced liver injury by redcuing lead burden, oxidative stress and inhibiting EGFR-AA three mechanisms needs further study.This topic aimed to utilize lead level changes, the degree of oxidative stress and inflammation to study the repairement effect of curcumin on lead indced liver damage, Oxidative stress as the breakthrough point was to build a juvenile rat model of lead poisoning, after administering curcumin treatment, body burden of lead, oxidative stress and degree of inflammation was detected. ICP-MS technique was used to detect lead levels in various body organs; chemical biology technology was used to detect antioxidant enzymes; protein western blot and RT-qPCR was used to detect EGFR-AA inflammatory pathways EGFR, ERK, CPLA2, COX-2 genes and protein expression and Arachidonic acid metabolites of 20-HETE, PGE2, EETS contents. The results show that curcumin could reduce the lead lever of the degree of liver pathology, liver tissue lead levels and increased levels of antioxidant enzymes, reduced lipid peroxidation, decreased EGFR, ERK, CPLA2, COX-2 gene and protein expression, it also decreased 20-HETE, PGE2 content and increased EETS. significantly compared with non-treatment groups.Results demonstrated that curcumin could increase the lead excretion of lead poisoning rats, reduce the body burden of lead, improve levels of antioxidant enzymes, decrease lipid peroxidation, curcumin also could inhibit protein and gene abnormal expression of EGFR-AA pathway in rats. In summary, lead-induced liver damage could be repaired by curcumin through the three mechanisms. This study contributed to a better understanding of the mechanism of toxicity of lead, and will lay the foundation for mechanism of curcumin treatment of lead poisoning and the clinical application of curcumin.