β-Carbolines That Accumulate in Human Tissues May Serve a Protective Role against Oxidative Stress

Abstract

␤-Carbolines are tricyclic nitrogen heterocycles formed in plants and animals as Maillard reaction products between amino acids and reducing sugars or aldehydes. They are being detected increasingly in human tissues, and their physiological roles need to be understood. Two ␤-carboline carboxylates have been reported to accumulate in the human eye lens. We report here on the identification of another ␤-carboline, namely 1-methyl-1-vinyl -2,3,4-trihydro-␤-carboline-3-carboxylic acid, in the lenses of some cataract patients from India. Analysis of these three lenticular ␤-carbolines using photodynamic and antioxidant assays shows all of them to be inert as sensitizers and effective as antioxidants; they quench singlet oxygen, superoxide and hydroxyl radicals and inhibit the oxidative formation of higher molecular weight aggregates of the test protein, eye lens ␥-crystallin. Such antioxidative ability of ␤-carbolines is of particular relevance to the lens, which faces continual photic and oxidative stress. The ␤-carboline diacid IV is also seen to display an unexpected ability of inhibiting the thermal coagulation of ␥-crystallin and the dithiothreitol-induced precipitation of insulin. These results offer experimental support to earlier suggestions that one of the roles that the ␤-carbolines have is to offer protection against oxidative stress to the human tissues where they accumulate.

Studies on Singlet Oxygen Formation and UVA Light-mediated Photobleaching of the Yellow Chromophores in Human Lenses

“…It is of interest that browning is markedly accelerated in dark brown and black brunescent cataracts, which may be due to the generation of singlet oxygen damage in these lenses. This would be consistent with the lower Trp levels in these lenses and the fact that several browning compounds isolated from dark brown cataracts are modi®ed Trp residues (Luthra et al, 1994;Pari et al, 2000).…”

Protective effects of Peganum harmala L. extract, harmine and harmaline against human low-density lipoprotein oxidation

“…As mentioned above, harmaline inhibited the maximal production of oxidation product and therefore protected the apolipoprotein moiety against alteration. These results were in agreement with Pari et al (2000) who showed that -carbolines could quench singlet oxygen, superoxide and hydroxyl radicals and inhibit the oxidative formation of higher molecular weight aggregates of the test protein.…”

Predictive modeling of the total deactivation rate constant of singlet oxygen by heterocyclic compounds

“…4). Despite the fact that they have been suggested as possible antioxidants [43], to the best of our knowledge there is no experimental (k t ) data for them. In aqueous solution, b-carbolines show an acid-base equilibrium with pK a around 7.…”