What is Cisplatin?
How it works
Cisplatin is a “chemotherapeutic agent” that can covalently bind with DNA using the purine base, mainly guanine, in a cross-link that leads to transcription inhibition, cell cycle arrest, and an apoptotic effect27. Cisplatin is responsible for the production of reactive oxygen species28. Absorption of cisplatin into the nuclear DNA binds two adjacent guanines in the same DNA strand, causing an inhibition of DNA synthesis and cell death29. Moreover, programmed cell death or apoptosis has been associated with several anticancer drugs, including cisplatin. This active form of cell death is characterized by morphological changes such as cell shrinkage, vacuolization, chromatin condensation, and DNA fragmentation, which often require the formation of new proteins called caspases30.
In our study, cisplatin seemed to affect the histological pattern of the pulp tissue. The histological examination of the pulp, injected with a single dose of Cisplatin, revealed a fatty degeneration and vacuolization of some areas of the odontoblastic layer and, in other areas, showed crowding in odontoblasts. Osteodentine was an idiopathic calcification inside pulp tissues; some areas showed hyaline degeneration. These changes were thought to be due to the mechanism of action of cisplatin that aims for cell death. Fibrosis of pulpal connective tissue with chronic inflammatory cells, which coincides with a previous study on the kidney that noticed there was an increase in the chronic inflammatory cells and fibrosis induced by injection with Cisplatin31. A study by Jiang et al. demonstrated that the DNA-damaging agent cisplatin lowered the contractile function of thoracic aortas and caused direct vessel wall damage and cytotoxicity towards smooth muscle cells32. This study agreed with our results that showed multiple dilated blood vessels of different sizes, engorged with blood, appearing with areas of vacuolization in the pulp tissue core.
How it works
L-carnitine is an essential amine in skeletal muscle metabolism as it is important in fatty acid metabolism, regulating caspase activity and expression. As mentioned, caspases are essential in apoptosis33. In the present study, the typical appearance of pulp tissue in the third group, which received L-carnitine before cisplatin injection, indicated that L-Carnitine has an anti-oxidant and anti-inflammatory role that protects the cells from the harmful effects of cisplatin34. In addition, L-Carnitine counteracts the induced fibrosis, which cisplatin can trigger35. Marilyn et al. reported that L-Carnitine causes vasodilation of human subcutaneous arteries, an effect that appears to be largely mediated by endothelial production of prostaglandins, but also seems to have a modest smooth muscle cell component at higher concentrations. Therefore, the beneficial cardiovascular effects of this compound may be related to vasodilation and improved blood flow36. Marilyn’s findings agreed with our results, as group III, that received a single dose of L-Carnitine before Cisplatin, showed dilation in the blood vessels of the pulp core.