Lycopene Interferes With Cardiac And Renal Function Damage Induced By Atrazine Exposure In Mice By Regulating MAPK Signal Pathway

Atrazine(ATR)is one of the most widely used broad-leaf weed herbicides with low cost in the world.Atrazine continuously accumulate in soil and water environment in the course of use.It poses a serious threat to animal and human health and can have toxic effects on a variety of organs systematically.Lycopene(LYC)is a kind of carotenoid with a variety of biological activities and antioxidant properties,which exists in a variety of red fruits and vegetables.It is widely distributed in the heart and kidney after intake.Lycopene plays an important role in the process of heart and kidney protection because of its strong anti-inflammatory and antioxidant effects.Cardiorenal syndrome is an important disease of organ crosstalk dysfunction found in recent years,but the specific mechanism of its occurrence has not been fully elucidated.In order to reveal the relationship between LYC antagonistic ATR and cardiorenal syndrome,21-day-old SPF Kunming mice were randomly divided into seven groups:): Con group(control group),Vcon group(solvent control group),L group(5mg/kg LYC group),A Ⅰ group(50mg/kg ATR group),AⅠ+L group(50mg/kg ATR+5mg/kg LYC group),AII group(200mg/kg ATR group)and AII+L group(200mg/kg ATR+5mg/kg LYC group).The mice were treated by continuous intragastric administration for 21 days.The study seeks to explore the toxic mechanism of ATR on cardiac and renal function injury and the antagonistic effect of LYC on ATR by observing the morphology,histopathology and ultrastructure of heart and kidney in mice,detecting the biomarkers related to heart and kidney injury,oxidative stress related factors,inflammation related factors and MAPK signal pathway related factors by ELISA,q RT-PCR and Western Blot.The experimental results show that:(1)LYC can relieve the ATR-induced structural damage to heart and kidney,including tissue swelling,glomerular atrophy,renal tubular epithelial cell swelling and inflammatory cell infiltration,myocardial myofibril rupture,myocardial nucleolysis,blurring of mitochondrial crest and cardiomyocyte apoptosis,further alleviating the histopathological changes of heart and kidney.(2)LYC can reduce the excessive secretion of serum and urine biomarkers of cardiac and renal function damage(NT-pro-BNP,c Tn-T,NGAL,Cys-C,Kim-1,TNF-α,IL-6)in mice with ATR-induced cardiorenal syndrome,showing obvious cardiorenal protective effect.(3)LYC can antagonize oxidative stress and inflammatory reaction in ATR-induced heart and kidney injury in mice,improve tissue oxidative stress,reduce the activation of inflammatory pathway related factors,reduce the expression of Nrf2 and inflammatory factors(IL-1 β,IL-18,TNF-α)in heart and kidney tissue,inhibit the activation of inflammatory related factors(PPAR α,NF κ B),and maintain the normal function of heart and kidney tissue.(4)LYC inhibits MAPK signal pathway activated by ATR exposure and reduces the expression of phosphorylated proteins(P38 MAPK,ERK,JNK)related to MAPK pathway,thus protecting the heart and kidney from cardiorenal syndrome induced by ATR.To sum up,ATR exposure can damage the structure and function of heart and kidney tissue,cause histopathological changes,increase the secretion of biomarkers related to cardiorenal dysfunction,cause tissue oxidative stress,inflammatory injury and a large number of accumulating of related inflammatory factors,and activate MAPK signaling pathway,further cause damage to the heart and kidney,and then lead to the occurrence of cardiorenal syndrome.LYC reduces the secretion of biomarkers of cardiorenal injury in serum and urine by resisting tissue oxidative stress,reducing inflammatory response and increasing the dephosphorylation level of MAPK-related proteins,so as to avoid the toxic effects of ATR on heart and kidney tissue and reduce the possibility of cardiorenal syndrome in mice.