Disparity of selenourea and selenocystine on methaemoglobinemia in non-diabetics and diabetics.

ABSTRACT

Organoselenium drugs like selenourea (SeU) and selenocystine (SeC) are found to exhibit several medicinal properties and have reported roles in the field of cancer prevention. However, studies related to their interactions with the major erythroid protein, haemoglobin (HbA) are still in dearth despite being of prime importance. In view of this, it was considered essential to investigate the interaction of these two anticancer drugs with Hb. Both the drugs showed significant changes in absorption spectra of Hb at wavelength of maximum absorption (λmax) 630 nm. SeU itself had no effect on the absorbance value at 630 nm with respect to time even with 400 µM concentration. However, it was rapidly converted to nanoselenium in presence of nitrite and there was an increase in the absorbance rate at 630 nm from 3.39 × 10-3 min-1 (without nitrite) to 8.94 × 10-3 min-1 in presence of nitrite (200 µM) owing to the generation of reactive oxygen species in the medium. Although the generation and increase in peak intensity at 630 nm in Hb generally indicates the formation and rise in the levels of methaemoglobin (metHb), nanoselenium was observed to follow a different path. Instead of causing oxidation of Fe2+ to Fe3+ responsible for metHb formation, nanoselenium was found to interact with the protein part, thereby causing changes in its secondary structure which is reflected in the increasing absorbance at 630 nm. SeC, however, showed a different effect. It was shown to act as a novel agent to reduce nitrite-induced metHb formation in a dose-dependent manner. The efficiency of SeC was again found to be less in diabetic blood samples as compared to the non-diabetic ones. For similar ratio of metHb to SeC (18), % reduction of metHb was found to be 27.46 ± 0.82 and 16.1 ± 2.4 for non-diabetic and diabetic samples, respectively, with a two tailed P-value much <0.05 which implies that the data are highly significant.