The protective effect of melatonin on benzo(a)pyrene-induced brain injury: role of apoptosis and autophagy pathways.

Benzo(a)pyrene (BaP), a toxic polycyclic aromatic hydrocarbon, is spread in different ways as an environmental pollutant. It has been proposed that BaP can induce toxicity through oxidative stress and apoptosis in vital organs. The present study evaluated the protective effect of melatonin, a circadian hormone of the pineal gland, on BaP-induced neurotoxicity focused on oxidative stress, autophagy, and apoptosis pathways. Thirty male mice in 5 groups were treated daily for 28 consecutive days: (I) control group (BaP and melatonin solvent), (II) BaP (75 mg/kg, orally), (III) and (IV) BaP + melatonin (10 and 20 mg/kg, i.p.), (V) melatonin (20 mg/kg). The oxidative stress markers were determined in the brain. Western blot was conducted for the level of LC3 II/I and Beclin1, as autophagy markers, caspase3 and Bcl2, as apoptosis proteins, and Sirt1 in the brain. The exposure of mice to BaP caused a marked increase in the malondialdehyde (MDA) level and decrease of glutathione (GSH) content in the brain. Furthermore, the Sirt1 level upregulated as well as LC3 II/I, Beclin1, and cleaved caspase3 proteins, while the level of Bcl2 did not change. Melatonin at 20 mg/kg concurrently with BaP restored the BaP alteration in the brain compared with the BaP group. In conclusion, BaP induced brain toxicity via the induction of oxidative stress, apoptosis, and autophagy, whereas melatonin afforded neuroprotection against BaP due to inhibition of these mechanisms.

Cytotoxic Effects of Ferula Latisecta on Human Glioma U87 Cells.

Glioblastoma multiforme (GBM) is the fatal type of astrocytic tumors with a survival rate of 12 months. The present study, for the first time, evaluated the cytotoxic impacts of Ferula latisecta (F. latisecta) hydroalcoholic extract on U87 GBM cell line. The MTT assay measured the cellular toxicity following 24- and 48 h treatment with various doses of F. latisecta (0-800 µg/mL). Apoptosis was evaluated by an Annexin V/propidium iodide (PI) staining 24 h after treatment by F. latisecta. Moreover, to determine the cellular metastasis of U87 cells, we used a gelatin zymography assay (matrix metalloproteinase [MMP]-2/-9 enzymatic activity). The outcomes showed that F. latisecta mitigated the viability of U87 cells in a concentration- and time-dependent manner with IC50 values of 145.3 and 192.3 µg/mL obtained for 24- and 48 h treatments, respectively. F. latisecta induced apoptosis in a concentration-dependent manner after 24 h. Also, MMP-9 activity was significantly decreased following 24 h after treatment concentration-dependently with no change in MMP-2 enzymatic activity. This study showed that F. latisecta induced cytotoxicity and apoptosis, and mitigated metastasis of U87 GBM cells. Hence, F. latisecta could be beneficial as a promising natural herb against GBM after further studies.