Crocin Attenuates Cisplatin-induced Liver Injury In The Mice

ObjectiveTo investigate the protective effect of crocin on cisplatin(CDDP)-induced liver and kidney injury and its mechanismsMethods30male nude mice of5weeks were randomly divided into5groups, including the control (saline) group, CDDP group, the low and high concentration crocin group (6.25mg/kg·d,25mg/kg·d),and positive control group(silymarin100mg/kg·d). Crocin and silymarin was administered to the mice once daily for7consecutive days. On day1, a single intraperitoneal injection of CDDP was given at the dose of10mg/kg body weight. After7days, all the mice were executed. Blood was collected immediately on the day of sacrifice for alanine aminotransferase(ALT), aspartate aminotransferase(AST), creatinine(Cr), and blood urea nitrogen(BUN) assay. The paraffin sections of liver and kidney were stained with HE staining and then observed by light microscope. The level of malondialdehyde(MDA) and glutathione(GSH) were detected. Also, the activity of superoxide dismutase (SOD), glutathione peroxidase(GSH-px), and catalase(CAT) were detected. The p-p38MAPK, p53, and caspase-3expressions of the liver and kidney were detected by immunohistochemical technique and Western blot essay.Result1. The effects of crocin on the serum biochemistry index of the mice damaged by CDDPCompared with the control group, the level of ALT, AST, BUN and Cr in the CDDP group were significantly increased (p<0.05,totally). Compared with the CDDP group, the level of ALT, AST, BUN and Cr in the crocin and silymarin group were significantly decreased(p<0.05,totally). There was no significant difference between the crocin group and positive control silymarin group (p>0.05,totally)2. The effects of crocin on the histomorphology of the liver and kidney in the mice damaged by CDDPLiver and kidney histopathology indicated that crocin could alleviated CDDP-induced focal tissue damage.3. The effects of crocin on the antioxidant system of the mice damaged by CDDPCompared with the control group, the level of MDA of the liver and kidney in CDDP group were significantly increased (p<0.05,totally). Compared with the CDDP group, the level of MDA in the crocin and silymarin group were significantly decreased (p<0.05,totally). There was no significant difference between the crocin group and positive control silymarin group (p>0.05,totally)A significant reduction in GSH of the liver and kidney was found in CDDP group, compared to the control group (p<0.05, totally). Compared with the CDDP group, the level of GSH in the crocin and silymarin group were significantly decreased(p<0.05,totally). There was no significant difference between the crocin group and positive control silymarin group (p>0.05,totally)4. The effects of crocin on the antioxidant enzyme activity of the mice damaged by CDDPCompared with the control group, the anctivity of SOD, GSH-px, and CAT of the liver and kidney in CDDP group were significantly decreased (p<0.05,totally). Compared with the CDDP group, the anctivity of SOD, GSH-px, and CAT in the crocin and silymarin group were significantly increased (p<0.05,totally). There was no significant difference between the crocin group and positive control silymarin group (p>0.05,totally)5. The effects of crocin on the expression of p-p38MAPK, p53and caspase3The p-p38MAPK, p53, and caspase-3expressions of the liver and kidney were significantly increased (p<0.05,totally) in CDDP group, compared to the control group. Compared with the CDDP group, the expressions of p-p38MAPK, p53, and caspase-3in the crocin and silymarin group were significantly decreased (p<0.05,totally). There was no significant difference between the crocin group and positive control silymarin group (p>0.05,totally)Conclusion1. Crocin (6.25mg/kg·d、12.5mg/kg.d) treatment significantly improved CDDP-induced hepatic damage as indicated by serum ALT and AST. Crocin treatment also significantly improved CDDP-induced kidney damage as indicated by serum BUN and Cr.2. Liver and kidney histopathology indicated that crocin (6.25mg/kg·d、12.5mg/kg.d) alleviated CDDP-induced focal damage.3. Crocin relieved CDDP-induced oxidative stress by reducing MDA level and recovering the levels of GSH and antioxidant enzymes such as SOD, GHS-px, and CAT.4. Immunohistochemical staining and Western blot analysis showed that crocin (6.25mg/kg·d、12.5mg/kg.d) significantly decreased the levels of phospho-p38mitogen-activated protein kinase (MAPK), tumor protein53(p53), and caspase-3.