Mechanism and Efficiency of Cell Death of Type II Photosensitizers: Effect of Zinc Chelation

A series of meso-substituted tetra-cationic porphyrins, which have methyl and octyl substituents, was studied in order to understand the effect of zinc chelation and photosensitizer subcellular localization in the mechanism of cell death. Zinc chelation does not change the photophysical properties of the photosensitizers (all molecules studied are type II photosensitizers) but affects considerably the interaction of the porphyrins with membranes, reducing mitochondrial accumulation. The total amount of intracellular reactive species induced by treating cells with photosensitizer and light is similar for zinc-chelated and free-base porphyrins that have the same alkyl substituent. Zinc-chelated porphyrins, which are poorly accumulated in mitochondria, show higher efficiency of cell death with features of apoptosis (higher MTT response compared with trypan blue staining, specific acridine orange/ethidium bromide staining, loss of mitochondrial transmembrane potential, stronger cytochrome c release and larger sub-G1 cell population), whereas nonchelated porphyrins, which are considerably more concentrated in mitochondria, triggered mainly necrotic cell death. We hypothesized that zinc-chelation protects the photoinduced properties of the porphyrins in the mitochondrial environment.

Pancreatic iron stores assessed by magnetic resonance imaging (MRI) in beta thalassemic patients

Purpose: To assess the correlation between MRI findings of the pancreas with those of the heart and liver in patients with beta thalassemia; to compare the pancreas T2* MRI results with glucose and ferritin levels and labile plasma iron (LPI). Materials and methods: We retrospectively evaluated chronically transfused patients, testing glucose with enzymatic tests, serum ferritin with chemiluminescence, LPI with cellular fluorescence, and T2* MRI to assess iron content in the heart, liver, and pancreas. MRI results were compared with one another and with serum glucose, ferritin, and LPI. Liver iron concentration (LIC) was determined in 11 patients' liver biopsies by atomic absorption spectrometry. Results: 289 MRI studies were available from 115 patients during the period studied. 9.4% of patients had overt diabetes and an additional 16% of patients had impaired fasting glucose. Both pancreatic and cardiac R2* had predictive power (p < 0.0001) for identifying diabetes. Cardiac and pancreatic R2* were modestly correlated with one another (r(2) = 0.20, p < 0.0001). Both were weakly correlated with LIC (r(2) = 0.09, p < 0.0001 for both) and serum ferritin (r(2) = 0.14, p < 0.0001 and r(2) = 0.03, p < 0.02, respectively). None of the three served as a screening tool for single observations. There is a strong log-log, or power-law, relationship between ratio of signal intensity (SIR) values and pancreas R2* with an r(2) of 0.91. Conclusions: Pancreatic iron overload can be assessed by MRI, but siderosis in other organs did not correlate significantly with pancreatic hemosiderosis. (C) 2011 Elsevier Ireland Ltd. All rights reserved.