| Zearalenone（ZEA）,a mycotoxin with estrogen-like effects,is widely found in cereal and other food crops.Long-term exposure to ZEA can cause various damages to the reproductive system,liver,kidneys,immune system and nervous system of animals.The liver is an important metabolic organ of the body.When ZEA is absorbed from the intestine,the first organ to reach is the liver.It has been reported that ZEA can cause liver damage and inflammation,and the main mechanism of ZEA’s toxicity to hepatocytes is oxidative damage.Resveratrol（RSV）is a common natural polyphenolic compound,which is widely present in plants such as Veratrum,Vitis,and Peanut.Studies have shown that RSV has antiinflammatory,antioxidant,anti-apoptotic,anti-tumor properties and other effects.RSV also has the characteristics of wide source,low price and high safety.In this experiment,mice were used as the research objects.40 clean-grade male BALB/c mice were randomly divided into control group（gavage with normal saline）,ZEA group（gavage with 40 mg/kg bw ZEA）.different concentrations of RSV（Five groups were treated with 50,100 or 200 mg/kg bw RSV by gavage）and ZEA（40 mg/kg bw ZEA by gavage）group,with 8 animals in each group.The protective effect and mechanism of RSV at different doses on liver injury and inflammation caused by ZEA were investigated,aiming to provide scientific basis for the study on effective ways of clinical prevention and control of ZEA toxicity.1.ZEA on liver damage and the protective effect of resveratrolIn order to explore the protective effect of ZEA on liver injury and RSV,the liver and serum samples of mice in each experimental group were collected,the anatomical lesions of the liver were observed,their organ coefficients were calculated.The histological conditions were observed by HE staining and electron microscopy,and serum levels were detected.The activity of AST,ALT and LDH was detected.The results showed that,compared with the control group,the liver anatomical lesions of the mice in the ZEA group showed congestion,black color and other lesions.Compared with ZEA group,RSV co-treated low dose group showed slight injury,and medium dose group and high dose group showed good macroscopic appearance.Compared with the control group,the liver coefficient of the mice in the ZEA group was significantly increased（P<0.01）;compared with the ZEA group,there was no significant difference in the liver coefficient of the low-dose group treated with RSV（P>0.05）.The middle-dose group and the high-dose group had no significant difference（P>0.05）.The dose group decreased significantly（P<0.05）.Compared with the control group,the liver of the mice in the ZEA group showed a large amount of congestion in the central vein,a small amount of inflammatory cell infiltration around the liver,edema changes in the liver cells,loose and light staining of the cytoplasm and other lesions.Compared with the ZEA group,in the RSV co-treated each group,the liver tissue lesions of the mice were alleviated,especially in the middle-dose and high-dose groups.Ultrastructural observation of liver tissue showed that,compared with the control group,ZEA group showed obvious nuclear shrinkage,nuclear membrane damage,mitochondrial swelling and mitochondrial crest disappearance,accompanied by the production of autophagosomes and other lesions.Compared with ZEA group,the lesion of RSV cotreatment group was reduced..Compared with the control group,the activities of serum AST,ALT and LDH in the ZEA group were significantly increased（P<0.01）;compared with the ZEA group,the activities of serum AST,ALT and LDH in the RSV co-treatment groups were significantly decreased（P<0.01）.The results show that ZEA can cause damage to the liver tissue structure in mice.RSV can effectively alleviate the liver damage caused by ZEA with a dose-response relationship.2.The antioxidant effect of resveratrol in alleviating ZEA-induced liver damageIn order to explore the effect of anti-oxidation on RSV in alleviating ZEA-induced liver damage,liver tissue samples were collected from mice in each experimental group.The content of MDA,the activities of SOD and CAT in the liver were detected by kit method,and the liver tissue was detected by qRT-PCR.The expression levels of Nrf-2,HO-1,γ-GCS and GSH-Px in liver tissue were detected by immunohistochemistry.The results showed that compared with the control group,the liver MDA content of the mice in the ZEA group was significantly increased（P<0.01）.Compared with ZEA group,RSV co-treatment had no significant difference in low dose group（P>0.05）,while RSV co-treatment in medium dose group significantly decreased（P<0.01）,high dose group significantly decreased（P<0.05）.Compared with the control group,the liver CAT activity of the mice in the ZEA group was significantly decreased（P<0.01）;Compared with ZEA group,RSV co-treated low-dose and high-dose groups were significantly higher（P<0.05）,medium dose group was significantly increased（P<0.01）.Compared with the control group,the SOD of the mice in the ZEA group was significantly decreased（P<0.05）;compared with the ZEA group,the RSV cotreatment medium-dose group was significantly increased（P<0.05）,and there was no significant difference between the high-dose and low-dose groups（P>0.05）.Compared with the control group,the expression levels of Nrf-2,HO-1,γ-GCS and GSH-Px in the liver of mice in the ZEA group were significantly decreased（P<0.01）.There was no significant difference in the expression levels of the above genes in the dose groups（P>0.05）.The middle dose group and high dose group were significantly increased（P<0.01）.Compared with the control group,the liver immunohistochemistry in the ZEA group showed that the Nrf-2 nuclear entry was significantly reduced;compared with the ZEA group,the Nrf-2 nuclear entry in the RSV co-treatment groups was significantly increased,especially in the middle and high dose groups.The results showed that ZEA had a serious oxidative damage effect on the liver.RSV could improve the oxidative stress caused by ZEA by up-regulating the expression of Nrf-2,especially RSV at 100 mg/kg bw had the best antioxidant effect.3.The anti-inflammatory effect of resveratrol in alleviating ZEA-induced liver damageIn order to explore the effect of anti-inflammatory effect on RSV in relieving ZEAinduced liver injury,liver and serum samples were collected from mice in each experimental group.The levels of serum IL-6,TNF-α and IL-1β were detected by ELISA,and qRT-PCR was used to detect the contents of serum IL-6,TNF-α and IL-1β.The gene expression levels of iNOS,COX-2 and NF-κB in liver tissue were detected,and the expression of NF-κB protein in liver tissue was detected by immunohistochemistry.The results showed that compared with the control group,the serum levels of IL-6,TNF-α and IL-1β in the ZEA group were significantly increased（P<0.01）.The contents of IL-1β were significantly or extremely significantly decreased（P<0.05 or P<0.01）,and TNF-α was extremely significantly decreased in the middle-dose group（P<0.01）,while there was no significant difference in TNF-α between the high-dose group and the low-dose group（P<0.01）.P>0.05).Compared with the control group,the expression levels of NF-κB,iNOS and COX-2 in the liver of mice in the ZEA group were significantly increased（P<0.01）.NF-κB and iNOS gene expressions were significantly decreased（P<0.01）,while NF-κB gene expression was significantly decreased in low-dose group（P<0.05）There was no significant difference in iNOS gene expression in low-dose group（P>0.05）.).Besides,there was no significant difference in gene expression between COX-2 low-dose and high-dose groups（P>0.05）,while the gene expression in the middle-dose group was significantly decreased（P<0.01）.Compared with the control group,the liver immunohistochemistry in the ZEA group showed that the NF-κB entry into the nucleus was significantly increased.Compared with the ZEA group,the NF-κB entry into the nucleus in the RSV co-treatment groups was significantly decreased,especially in the middle and high dose groups.The results showed that ZEA had an inflammatory injury effect on the liver.RSV had a protective effect on the liver inflammatory injury caused by ZEA,especially RSV at 100 mg/kg bw had the best antiinflammatory effect.RSV ameliorated ZEA-induced inflammatory injury by down regulating of the NF-κB expression.Conclusion:ZEA has serious oxidative and inflammatory damage to the liver.RSV has a protective effect on liver damage caused by ZEA,especially RSV at 100 mg/kg bw has the best protective effect.RSV exerts its anti-oxidative and inflammatory effects on the liver caused by ZEA by up-regulating of the Nrf-2 and down-regulating of the NF-κB signaling pathway. |
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