Marcin F. Osuchowski

Alterations in Regional Brain Neurotransmitters by Silymarin, a Natural Antioxidant Flavonoid Mixture, in BALB/c Mice

Silymarin, a natural antioxidant flavonoid mixture, exerts anti-inflammatory effects in the liver and hinders tumor formation. The effect of this flavonoid mixture on the central nervous system is unknown, although antioxidants are considered beneficial. Brain amines and metabolites were studied after a short-term silymarin treatment. BALB/c mice were intraperitoneally treated with 0, 10, 50, or 250 mg/kg of silymarin per day for 5 days. High-performance liquid chromatography coupled with electrochemical detection was performed to determine concentrations of norepinephrine (NE), dopamine (DA), dioxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxytryptamine (5-HT, serotonin) and 5-hydroxyindoleacetic acid (5-HIAA) in discrete brain regions. Analyses showed increased 5-HT levels in the cortex and increased DA and NE levels in the cerebellum in the highest dose group. Results indicated lack of general adverse effect on the brain amine metabolism and suggest that silymarin may have marginal serotonergic, dopaminergic, and noradrenergic effects.

Inhibition of Serine Palmitoyltransferase by Myriocin, a Natural Mycotoxin, Causes Induction of C-Myc in Mouse Liver

Myriocin, a fungal metabolite isolated fromMyriococcum albomyces, Isaria sinclairi, and Mycelia sterilia, is a potent inhibitor ofserine palmitoyltransferase (SPT), a key enzyme in de novo synthesis of sphingolipids. To evaluatethe biological effects of myriocin in vivo, we investigated the levels of free sphingoid basesand expression of selected genes regulating cell growth in mouse liver. Male Balb/c mice,weighing 22 g were injected intraperitoneally with myriocin at 0, 0.1, 0.3, and 1.0 mg kg-1 bodyweight daily for 5 days. Animals were euthanized 24 hours after the last treatment. Levelsof plasma alanine aminotransferase and aspartate aminotransferase were not significantlyaltered by the treatment. A dose-dependent decrease in free sphinganine but not sphingosine wasdetected by high performance liquid chromatography in both liver and kidney. The decreaseof free sphinganine paralleled the decrease in SPT activity. Reverse transcriptasepolymerase chain reaction analysis on liver mRNA revealed an increase in expression of c-myc,but no changes in tumor necrosis factor α, transforming growth factor β, andhepatocyte growth factor. Results showed that myriocin blocked de novo synthesis of sphingolipids in vivoby SPT inhibition and induced c-myc expression in liver.