Punicalagin ameliorates the elevation of plasma homocysteine, amyloid-ß, TNF-α and apoptosis by advocating antioxidants and modulating apoptotic mediator proteins in brain.

The present study investigated the neuroprotective role of punicalagin, a major polyphenolic compound of pomegranate on methionine-induced brain injury. Hyperhomocysteinemia (HHcy) was induced in two months old male BALB c mice by methionine supplementation in drinking water (1 g/kg body weight) for 30 days. Punicalagin (1 mg/kg) was injected i.p every other day concurrently with methionine. Punicalagin significantly prevented the rise in the levels of homocysteine, amyloid-ß and TNF-α. HHcy is associated with a decrease in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (PGx) and glutathione reductase (GR) and glutathione (GSH) levels in the brains of methionine-treated mice while these antioxidants are increased by punicalagin supplementation. The treatment with punicalagin significantly decreased oxidative stress as indicated by decreased malondialdehyde and protein carbonyl formation in the brain. Compared with methionine-treated animals, mice that treated with methionine and punicalagin remarkably displayed less apoptosis, indicated by the lower level of proapoptotic protein (Bax, caspases- 3, 9 and p53) and higher levels of antiapoptotic Bcl-2 protein than those in hyperhomocysteinemic mice. The potent bioactivity of punicalagin extends to protect neuronal DNA as evidenced by the inhibition of the increase of comet parameters compared to the methionine-treated mice. In conclusion, punicalagin protected from methionine-induced HHcy and brain damage with an ability to repress apoptosis by modulating apoptotic mediators and maintaining DNA integrity in the brain of mice.

Melatonin controls oxidative stress and modulates iron, ferritin, and transferrin levels in adriamycin treated rats.

AIM: Chemotherapy with adriamycin (ADR) is limited by its iron-mediated pro-oxidant toxicity. Because melatonin (MLT) is a broad spectrum antioxidant, we investigated the ability of MLT to control iron, its binding proteins, and the oxidative damage induced by ADR. MAIN METHODS: ADR was given as single i.p. dose of 10 mg kg(-1) body weight into male rats. MLT at a dose of 15 mg kg(-1) was injected daily for 5 days before ADR treatment followed by another injection for 5 days. Biochemical methods were used for this investigation. KEY FINDINGS: ADR injection caused elevations in plasma creatine kinase isoenzyme, lactic dehydrogenase, and aminotransferases, iron, ferritin, and transferrin. These changes were associated with increases in lipid peroxidation and protein oxidation as well as decreases in glutathione (GSH) levels and glutathione-S-transferase (GST) activity, while glutathione peroxidase (GSH-Px), and catalase (CAT) activity were elevated in the heart and liver of ADR treated rats. In the MLT+ADR group, the cardiac and hepatic function parameters and the levels of iron, transferrin and ferritin in plasma were normalized to control levels. The rats that were subjected to MLT+ADR had normalized CAT and GSH-Px activity and decreased TBARS and protein carbonyl levels compared the group only treated with ADR. GST activity and GSH concentration in the heart and liver were normalized when MLT accompanied ADR treatment. SIGNIFICANCE: MLT ameliorated oxidative stress by controlling iron, and binding protein levels in ADR treated rats demonstrating the usefulness of adriamycin in cancer chemotherapy and allowing a better management of iron levels.