The inhibition of heme oxigenase-1 (HO-1) abolishes the mitochondrial protection induced by sesamol in LPS-treated RAW 264.7 cells.

Redox impairment and mitochondrial dysfunction have been seen in inflammation. Thus, there is interest in studies aiming to find molecules that would exert mitochondrial protection in mammalian tissues undergoing inflammation. Sesamol (SES) is an antioxidant and anti-inflammatory molecule as demonstrated in both in vitro and in vivo experimental models. Nonetheless, it was not previously demonstrated whether and how SES would cause mitochondrial protection during inflammation. Thus, we investigated here whether a pretreatment (for 1 h) with SES (1-100 μM) would prevent mitochondrial impairment in lipopolysaccharide (LPS)-treated RAW 264.7 cells. It was also evaluated whether the heme oxigenase-1 (HO-1) would be involved in the effects on mitochondria induced by SES. We found that SES reduced the levels of lipid peroxidation and protein nitration in the membranes of mitochondria obtained from LPS-treated RAW 264.7 cells. SES also attenuated the production of superoxide anion radical (O2-•) and nitric oxide (NO•) in this experimental model. SES suppressed the LPS-elicited mitochondrial dysfunction, as assessed through the analyses of the activities of the mitochondrial complexes I and V. SES also abrogated the LPS-induced decrease in the levels of adenosine triphosphate (ATP) and in the mitochondrial membrane potential (MMP). SES induced mitochondria-related anti-apoptotic effects in LPS-treated cells. Besides, SES pretreatment abrogated the LPS-triggered inflammation by decreasing the levels of pro-inflammatory proteins. The SES-induced mitochondria-associated protection was blocked by the specific inhibitor of HO-1, ZnPP IX (20 μM). Therefore, SES induced mitochondrial protection in LPS-treated cells by a mechanism involving HO-1.