Study on Toxicity Test of Rats with R-α-Lipoic Acid Injection

OBJECTIVE To study the toxicity of R-α-lipoic acid(R-α-LA) in rats by intravenous injection long-term consecutive administration and explore the mechanism of blood platelet reduction. METHODS One hundred eighty Rats were randomly divided into 6 groups:the control group, the R-α-LA low dose group, the R-α-LA medium dose group, the R-α-LA high dose group, the L-LA control group and the LA control group. Rats were administered for 4 weeks by intravenous injection. Same animals were observed during 4 weeks after drug withdrawal. Samples were tested after the end of drug administration. RESULTS It showed toxic symptoms such as decreased autonomic activity, salivation, hair loss, and slow weight gain in R-α-LA high dose group, L-LA control group and LA control group. These toxic symptoms could be recovered during recovery period. The platelet counts in R-α-LA high dose group and LA control group were reduced. But it recovered during recovery period. It showed mild liver function damage and hepatocyte degeneration in R-α-LA high dose group, L-LA control group and LA control group. The L-LA control group of liver cell degeneration was heaviest. Liver damage was alleviated after recovery period. The pathological results of the R-α-LA high dose group showed that the number and morphology of megakaryocytes was normal and the levels of platelet-related antibody IgG did not change in serum. The level of reactive oxygen species(ROS) in platelets was accumulated in R-α-LA high dose group. CONCLUSION The maximum non-toxic response dose of the R-α-LA was 40 mg·kg^-1. Its thrombocytopenia may be caused by non-immune mechanisms.