Protective role of vitamin C in diazepam-induced apoptosis in rat thymocytes

Abstract

Diazepam, a peripheral-type benzodiazepine receptor ligand, is widely used as a therapeutic agent. On the other hand, peripheral-type benzodiazepines have been shown to induce apoptosis in different immune cell types. In this study, we examined the possible protective role of vitamin C in diazepam-induced apoptosis and evaluated the cellular content of glutathione during this process. Rat thymocytes were incubated for 24 hours with diazepam and increasing concentrations of vitamin C or with diazepam alone. The exposure to diazepam resulted in an increase in apoptotic cell death and decrease in glutathione content in rat thymocytes. Vitamin C was effective in ameliorating the effect of diazepam in rat thymocytes by decreasing the proportion of apoptotic cells and increasing the cellular content of glutathione. These results suggest that vitamin C reduced the diazepam-induced apoptosis in rat thymocytes by restoring the cellular content of glutathione, which may be useful in preventing the diazepam-induced immunosupression (Tab. 1, Fig. 1

High dietary intake of vitamin C suppresses age-related thymic atrophy and contributes to the maintenance of immune cells in vitamin C-deficient senescence marker protein-30 knockout mice

“…There is a significant age-associated increase in apoptosis that affects the double-negative cell population of thymocytes, partly due to the elevated expression of the cell death gene caspase-3 in aged mice ( 35 , 36 ) . VC has been shown to inhibit thymocyte apoptosis by up-regulating the expression of the anti-apoptotic protein B-cell lymphoma-2 ( 37 – 39 ) . We found that the total number of thymocytes and the number of double-positive cells and CD4 + or CD8 + SP thymocyte subpopulations were markedly higher in the 0·2 % VC group than in the 0·02 % VC group after 1 year of dietary treatment, possibly reflecting the inhibitory effect of high-dose dietary VC intake on the apoptosis of thymocytes through the induction of B-cell lymphoma-2.…”

Lorazepam induces acinar cells apoptosis of rat parotid glands

“…Similar to the present study, Pavlovic et al (2012) evaluated the apoptotic power of BZDs on rat thymocytes, since they incubated cells for a twenty-four-hour period with a BZD. After this period, the authors found that exposure to the drug resulted in an increase in cell death by apoptosis.…”

The Role of Anesthetic Drugs in Liver Apoptosis

“…a)Normal hepatocytes counteract apoptosis by neutralizing free oxygen species using agents like vitamin C and vitamin E; ferritin, glutathione, and a number of enzymes; as mentioned before, administration of vitamin C could suppress the apoptotic effects of benzodiazepines through "restoration of cellular glutathione reservoirs" (4, 118, 126-129). …”