The Study On Chemopreventive Effect Of Curcumin On Hepatotoxicity Induced By Microcystin In Fujian

AbstractObjective: To investigate the acute and subchronical hepatotoxicity of microcystinfrom cyanobacteria blooms in Fujian in mice and rats ;To investigate the preventiveeffect of curcumin on hepatotoxicity induced by the microcystin from cyanobacteriablooms in Fujian ;And finally to study the possibility of curcumin on preventtingmicrocystin hepatotoxicity in the area where liver cancer incidence is high.Method:1. The microcystin-LR and microcystin-RR concentration of microcysty extract from cyanobacteria blooms in Fujian were detected in HPLC.2. The microcysty extract from cyanobacteria blooms in Fujian ip LD₅₀ was detected by sequential method.3. Eighty kunming male mice were weighted and randomly assigned to four group based on body weight and were administered intraperitoneally injected with microcysty extract from cyanobacteria bloom(dose is respectively 0, 0.1,0.3,0.6 LD₅₀).Three hours later, the mice were sacrified. the liver was immediately removed and examined grossly. Blood sample were collected and tested for ALT, AST, LDH.4. Fifty-two kunming male mice were randomly assigned to four group based on body weight. Groups were respectively ig 20g/kg curcuma, 300mg/L curcumin and the others is ig. physiological saline for 7 days. On the 8^th day, the mice were administered intraperitoneally injected with the microcysty extract (dose is 0.6 LD₅₀) except the control group. Three hours later, the mice were sacrified andtested for ALT, AST, LDH, SOD, MDA and GST in the hepatic homogenate.5. Fifty Spraue-Damley male rats were randomly assigned to five group based on body weight. MCE group and three curcumin groups were administered intraperitoneally injected with 1/100 LD50 dose of MCE. The latter were ig 100, 200, 400mg/kg curcumin. The control group was ip physiological saline and ig 0.5% sodium carboxymethycellulose. The experiment went on to 35 days. On the 36th day, The rats were sacrified, the blood and liver were immediately removed and tested for the active level of ALT, AST, LDH, SDH, GSH, GSH-PX, GST, SOD, MDA and the expressive level of C-jun, C-fos,Bax,Bcl-2.Result1.The microcystin-LR concentration of microcystis extract from cyanobacteria blooms in Fujian was 40μg /ml, but microcystin-RR was not detected.2.The microcystins from cyanobacteria blooms in Fujian ip LD50 was 42μg /kg(MC-LR).3. The ALT, AST, LDH level in serum of the mice administered intraperitoneally injected with microcystis extract from cyanobacteria blooms in Fujian in three hours significantly increased(P<0.05), and the liver structure was damaged. It showed that there exist the dose-effect relationship between microcystin and liver injury and ALT, AST, LDH were sensitive indexs reflected the liver injury.4.The level of ALT,LDH,GST MDA in hepatic homogenate on curcumin groups were signifinantly decreased (P<0.05)and SOD were signifinantly increased (P<0.05). It showed that curcumin can prevent the hepatotoxicity induced by the microcystin.5.The liver coefficent and SDH in serum of the rats injected by 1/100 LD50 dose of microcystis extract were signifinantly higher than the control, meanwhile,the SOD level in serum were signifinantly decreased (P<0.05)and the liver structure was damaged.6.The liver weight, SDH and GST level of the rats ig with 200mg/kg curcumin were significantly lower (P<0.05)and the SOD level was significantly higher(P<0.05) than the rats only injected by the microcystis extract.7.The SDH in the rats ig with 100mg/kg curcumin significantly lower than the rats only injected by the microcystis extract.but significantly higher than the control group.8.The liver weight, liver coefficent and SDH level in the rats ig with 400mg/kg curcumin were significantly higher than the control and the GST level was significantly lower than the rats only injected by the microcystis extract.Conclusion1. The microcystins from cyanobacteria blooms in Fujian mainly contain MC-LR. The microcystins ip LD50 was 42μg /kg (MC-LR).2.Acute hepatotoxicity and subchronic hepatotoxicity was occurred when the rats exposured to 0.6LD50 and 0.01 LD50 dose of microcystis extract from cyanobacteria blooms in Fujian, respectively.3.The curcumin can prevent the oxidative damage in liver caused by microcystin from cyanobacteria blooms in Fujian.Its mechanism probably is that curcumin has anti-free radicle effect and antioxidation effect.4. Curcumin effect is ambidirectiona dominance. The lower dose of curcumin groups represent preventive effect while the high dose of curcumin group represents some toxicity when exposed to MC at the same time.5. It is possible to use curcumin to prevent the MC hepatotoxicity in the area where liver cancer incidence is high.