Table 2.
In Vitro Evidence of the Interplay of Endocannabinoids and Oxidative/Nitrative Stress
| Model | Changes in eCB level | Changes in cannabinoid receptor expression | Changes in oxidative stress markers following eCB targeted treatment | Ref. |
|---|---|---|---|---|
| Cultured mouse cortical neurons | Not measured | Not measured | CB1/CB2 activation by WIN 55,212-2 or by AEA reduced neuronal cell death and attenuated oxidative stress induced by Fe2+. Protection was abolished by the administration of rimonabant. | (165) |
| PC12 pheochromocytoma cell line | Not measured | Not measured | 6-OHDA-induced cell death was attenuated by AEA. | (217) |
| Rat glioma C6.9 cell line and primary rat cortical astrocytes | Not measured | Not measured | CBD treatment induced apoptosis in glioma cells via stimulation of ceramide synthesis; however, It did not affect viability of primary astrocytes. Long-term CBD incubation prevented H2O2-induced cell loss and abrogated sensitization to oxidative stress in serum-deprived astrocytes. | (45) |
| C6 glioma cell line | Not measured | Not measured | THC dose-dependently increased cell damage and death in the presence of agents generating ROS in a CB1-mediated manner. | (110) |
| Murine microglial BV-2 cell line or primary rat microglia culture | Not measured | High expression of CB2 in both BV-2 cells and primary microglia cells | Both CB1 and CB2 agonists attenuated LPS-induced iNOS expression, NO production and ROS generation. | (287) |
| Microglial BV-2 cell line | Not measured | Not measured | CBD and THC repressed the expression of several proinflammatory genes (CCL2, CCL7, CXCL14, CCL6, and CCL9). Interestingly, the authors found and increased ROS formation in BV-2 cells induced by CBD via the upregulation of genes involved in redox homeostasis. | (157) |
| Microglial BV-2 cell line | Not measured | Not measured | CBD and THC decreased the production and release of IL-1β, IL-6, and IFN-β following LPS challenge. CBD, but not THC, reduced the activity of the NF-κB pathway and activated STAT3 signaling. | (175) |
| Primary mouse microglia culture | Not measured | Not measured | NADA prevented ROS formation and PGE2 generation, whereas AEA exerted the opposite effects in LPS-primed primary microglial cells. | (237) |
| Human primary mDC and pDC | High expression of FAAH in pDC cells derived from MS patients. | High expression of CB2 in mDCs and pDCs originated from MS subjects. | mDCs produced high level of IL-6 and IL-12, whereas pDCs accounted for lower levels of IFN-γ in MS subjects compared with healthy controls. AEA inhibited cytokine production of dendritic cells as well as their ability to generate Th1 and Th17 lineages. | (53) |
6-OHDA, 6-hydroxydopamine; AEA, anandamide; CBD, cannabidiol; CCL, C-C motif chemokine; H2O2, hydrogen peroxide; IFN, interferon; IL, interleukin; iNOS, inducible nitric oxide synthase; LPS, lipopolysaccharide; mDC, myeloid dendritic cell; MS, multiple sclerosis; NADA, N-arachidonoyl dopamine; NFκB, nuclear factor kappa-light-chain-enhancer of activated B cells; NO, nitric oxide; pDC, plasmacytoid dendritic cell; PGE2, prostaglandin E2; ROS, reactive oxygen species; STAT3, signal transducer and activator of transcription 3; Th1, T helper 1; Th17, T helper 17.