Hepatic toxicity of TAT-P53 fusion protein in mice

OBJECTIVE: To study the potential toxicity of TAT-fused protein drugs. METHODS: B16 melanoma bearing mice were established via subcutaneously injection of B16 tumor cells in C57 mice. TAT-ODD-P53, TAT-P53 and P53 fusion proteins were used for anticancer therapy at the dose of 5 mg·kg^-1 by ip injection for 12 d. Twenty-four hours after the last injection, animals were executed and serum samples were harvested for aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), total protein (TP), albumin (Al), glucose (GLU), urea nitrogen (UREA), creatinine (Cre) and cholesterol (CHO). RESULTS: The level of AST and ALT in serum in TAT-P53 and P53 treatment groups was higher than that of in normal control group, but was higher in TAT-ODD-P53 treated mice than that of normal mice, and lower than in TAT-P53, P53 and saline buffer treatment groups. The TG level of P53 and TAT-P53 treated mice was higher than that of normal control mice or saline buffer and TAT-ODD-P53 treated tumor bearing mice. Moreover, the TP level from P53, TAT-P53 and saline treated mice was higher than that of normal control and TAT-ODD-P53 treated animals. There was no significant difference in Al, GLU, UREA, Cre and CHO between TAT-ODD-P53, TAT-P53 and P53 fusion protein groups compared with normal control group. CONCLUSION: TAT-P53 has potential toxicity to the liver.