METHODS: HepG2 cells were treated with different concentrations of KMF and 0.5 mM palmitate (PA) for 24 h. The mRNA and protein levels of genes involved in lipid metabolism were evaluated using real-time PCR and western blot. The expression of Nrf2 was silenced using siRNA.
RESULTS: Data indicated that KMF (20 μM) reversed PA-induced increased triglyceride (TG) levels and total lipid content. These effects were accompanied by down-regulation of the mRNA and protein levels of lipogenic genes (FAS, ACC and SREBP1), and up-regulation of genes related to fatty acid oxidation (CPT-1, HADHα and PPARα). Kaempferol significantly decreased the levels of the oxidative stress markers (ROS and MDA) and enhanced the activities of antioxidant enzymes SOD and GPx in PA-challenged cells. Luciferase analysis showed that KMF increased the transactivation of Nrf2 in hepatocytes. The results also revealed that KMF-mediated activation of Nrf2 target genes was suppressed by Nrf2 siRNA. Furthermore, Nrf2 siRNA abolished the KMF-induced reduction in ROS and MDA levels in PA treated cells. In addition, the inhibitory effect of KMF on TG levels and the mRNA and protein levels of FAS, ACC and SREPB-1 were significantly abolished by Nrf2 inhibition. Nrf2 inhibition also suppressed the KMF-induced activation of genes involved in β oxidation (CPT-1 and PPAR-α).
CONCLUSION: The results suggest that KMF protects HepG2 cells from PA-induced lipid accumulation via activation of the Nrf2 signaling pathway.
CASE PRESENTATION: We described a 43 years old male who presented with a right mastoid swelling, nine years after a right retro-sigmoid craniotomy and excision for a cerebellopontine angle meningioma. He also had multiple cranial neuropathies involving trigeminal, facial and vestibulocochlear nerves. Temporal bone CT and MRI showed features suggestive of cholesterol granuloma with extensive bony erosions. He was treated with surgical excision and drainage where bone wax residues were found intraoperatively. Histopathological analysis of the lesion confirmed the diagnosis of cholesterol granuloma. Post-operatively, the mastoid swelling resolved and his recovery was uneventful.
CONCLUSION: Our case showed that CG could manifest as a complication of bone wax usage in a neurosurgical procedure. Even though further study is needed to draw a definitive conclusion on this theory, we believe this paper will contribute to the current literature as it is the only reported case of cholesterol granuloma with bone wax as the possible causative agent. This is important so that surgeons are aware of this potential complication and use this haemostatic agent more judiciously.