In vitroantioxidant capacity and antigenotoxic properties of protoporphyrin and structurally related tetrapyrroles

Abstract

The antioxidant properties of protoporphyrin IX and related tetrapyrroles are poorly characterized. Therefore, eight tetrapyrroles, five of which are produced in vivo, were tested to assess their antioxidant capacities in the Salmonella reverse mutation, TEAC, FRAP and ORAC assays. Tertiary-butyl hydroperoxide (tert-BOOH) in the presence or absence of metabolic activation (±S9) was added to Salmonella strain TA102 together with the test compounds. In the absence of metabolic activation, the order of effectiveness was protoporphyrin > biliverdin > bilirubin ditaurate > bilirubin > biliverdin dimethyl ester > stercobilin > bilirubin dimethyl ester > urobilin. In the presence of S9, the effectiveness was reversed, with urobilin > biliverdin dimethyl ester > bilirubin dimethyl ester > stercobilin > biliverdin > bilirubin > bilirubin ditaurate > protoporphyrin. In the antioxidant capacity assays FRAP, TEAC and ORAC, mainly bilirubin, bilirubin ditaurate, biliverdin and protoporphyrin showed antioxidant activity. This study reports that previously untested tetrapyrroles of related structure prevent oxidatively induced genotoxicity, and for some, novel underlying mechanisms of antioxidant action were revealed. These results support the physiological importance and biological relevance of tetrapyrroles including protoporphyrin that might act as antioxidants, protecting from oxidatively induced DNA damage, particularly in the tissues/organs where they accumulate.

Long-Term Acclimation to Iron Limitation Reveals New Insights in Metabolism Regulation of Synechococcus sp. PCC7002

“…Instead, they could play a key role in detoxification of reactive oxygen species (Busch and Montgomery, 2015), that are produced as a result of the low capacity for electron transfer under Fe limitation. Indeed, protoporphyrin and other tetrapyrroles have been reported to have antioxidant properties (Mölzer et al, 2012). This lead us to hypothesize that the up-regulation of genes involved in porphyrin and chlorophyll metabolism under severe-Felim is reflected in the increase of the energetically detached light harvesting complexes that accumulate in the cells under severe-Felim reported by Schrader et al (2011).…”

Physical and chemical interactions between bile pigments and polyaromatic mutagens

“…129,130 The monolayers exhibit the brush border associated with the intestinal epithelia on the apical membrane and express most of the digestive enzymes and transporters present in the small intestine. 20,21 The apparent permeability (P app ) of small molecules across the monolayer has been shown to directly correlate to the compound's in vivo oral bioavailability.…”

“…[15][16][17][18][19][20][21] High concentrations of 1.1 (UCB) in the blood and bodily tissues leads to serious health problems such as jaundice, athetoid cerebral palsy, and hearing loss or deafness, particularly in newborn infants where the blood-brain barrier is not yet well formed and so may allow bilirubin to enter the brain. 3,15 The beneficial biological effects of BPs and their derivatives have been of mounting interest recently as their potent anti-mutagenicity, 15,18,19,21 and anti-oxidant properties 18,[22][23][24][25][26][27][28] come to light as well as their ability to bind to certain important enzymes.…”

“…These properties have been exploited in nanomaterials comprising metal and BF 2 complexes of dipyrrolylmethenes (BODIPY) 177 which generate a strongly polarised -electron system, and have proved useful as optical limiters, 178 sensors, fluorescent markers, 179,180 photosensitisers, 181,182 antioxidants, 183 and laser radiation limiters. 184,185 Other important pyrrole containing compounds, for example, bile pigments and their dimethyl esters, are also reported in many reviews of their potential biological properties, such as antioxidant [18][19][20]183 and anti-mutagenic acivities 15,18,19,186 . In spite of these promising properties and a variety of syntheses which aim to optimise the yield and efficiency, the need of pyrroles and dipyrroles for chemical interaction studies is not commercially available.…”

“…14,15,19,20,186 Furthermore, recent studies report that 6.7 (UCB) is a potent inhibitor of cytochrome P450 2A activities, 30,254 which is also known to contribute to the activation of some environmental carcinogens 36,255,256 . Bulmer et al 14 used the S9 fraction of rat liver homogenate and bacterial cultures to test the anti-mutagenic properties of 6.7 (UCB) and 6.8 (BV) and showed that both compounds efficiently inhibited revertant growth.…”