Abstract
To test the pharmacokinetics and toxicology of whole organs and tissues after intradiscal injection of simvastatin in rabbits. To provide the information needed to support human clinical trials. Twelve male and twelve female rabbits were randomly divided into four groups: control group (0 mg/ml), low dose group (0.1 mg/ml), medium dose group (1 mg/ml) and high dose group (10 mg/ml). Simvastatin at different concentrations of 10 μl was injected into L3/4, L4/5 and L5/6 intervertebral discs in each group. Poly (ethylene glycol) -poly (lactic-co-glycolic acid) -poly (ethylene glycol) (PEG-PLGA-PEG) polymer as the drug carrier. The pharmacokinetics of blood samples were measured by LC-MS/MS. Cerebrospinal fluid was obtained and the drug concentration was measured. Blood routine, blood biochemistry and urine of all animals were analyzed and evaluated. The heart, kidney, liver and spleen of each animal were observed and weighed. The intervertebral disc tissues were stained with hematoxylin and hematoxylin (H&E), and then qualitatively analyzed by optical microscopy. 28 days after intradiscal injection of simvastatin, 28 days after simvastatin intradiscal injection, there was no significant difference between the weight, food residue, blood routine, blood biochemistry, urine routine results and the weight of each organ in the four groups (p > 0.05). The serum concentration of simvastatin is lower than the lowest measurable concentration. The histological score of the intervertebral disc in the high-dose group was significantly higher than that in the other three groups at 28 days (p < 0.05). Three doses of simvastatin were injected into male and female animals respectively, showing no toxic effects. Microscopic histological evaluation of the intervertebral disc showed that the high dose group (10 mg/ml) had damage to the intervertebral disc tissue.
Highlights
Lower back pain (LBP) is a worldwide epidemic disease (Murray et al, 2013)
The food residues of all rabbits fluctuated with time, but there was no significant difference in the food residues between each group of animals (p > 0.05, Figure 3A,B)
Blood was taken from different groups of animals at different time points to obtain plasma, and the simvastatin content in the plasma was detected by liquid phase mass spectrometry. These results indicate that simvastatin was not detected in the blood in rabbits with different concentrations of simvastatin. (p < 0.05 represent statistically significant differences, n 3)
Summary
Lower back pain (LBP) is a worldwide epidemic disease (Murray et al, 2013). If the course of disease exceeds three months, it is called chronic low back pain. In the United States, LBP is one of the most frequently used opioids other than tumors (Andersson, 1981; Ringwalt et al, 2014). The main cause of LBP is the abnormal growth of nerve fibers into intervertebral discs, ligaments, articular processes, and other joints, causing pain below the costal margin and above the wrinkles below the hip. The main cause of LBP is from pain caused by degenerative disc (Adams, 2004), which accounts for more than 40% of LBP. Non-specific LBP caused by disc disease is called discogenic low back pain (DLBP)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
