Skin tumorigenic potential of benzanthrone: Prevention by ascorbic acid

Dwivedi, Neelam; Kumar, Sandeep; Ansari, Kausar M.; Khanna, Subhash K.; Das, Mukul

doi:10.1016/j.fct.2013.07.014

Cited by 5 publications

(3 citation statements)

References 44 publications

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“…Dwivedi et al (2013) reported measurable AHH and EROD activities in Swiss Albino female mice skin (0.34 ± 0.03 pmol/min/mg protein and 0.28 ± 0.02 pmol/min/mg protein, respectively; not clear whether this refers to S9 or total homogenate protein) which was reduced by topical treatment with commercial benzanthrone (150 nmol/mouse twice weekly for 30 weeks), the reduction of which was (partially or totally, respectively) prevented by simultaneous topical treatment with ascorbic acid (amount not given).…”

Section: Xenobiotica-metabolizing Enzymes In the Mouse Skinmentioning

confidence: 99%

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Xenobiotica-metabolizing enzymes in the skin of rat, mouse, pig, guinea pig, man, and in human skin models

2018

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Studies on the metabolic fate of medical drugs, skin care products, cosmetics and other chemicals intentionally or accidently applied to the human skin have become increasingly important in order to ascertain pharmacological effectiveness and to avoid toxicities. The use of freshly excised human skin for experimental investigations meets with ethical and practical limitations. Hence information on xenobiotic-metabolizing enzymes (XME) in the experimental systems available for pertinent studies compared with native human skin has become crucial. This review collects available information of which—taken with great caution because of the still very limited data—the most salient points are: in the skin of all animal species and skin-derived in vitro systems considered in this review cytochrome P450 (CYP)-dependent monooxygenase activities (largely responsible for initiating xenobiotica metabolism in the organ which provides most of the xenobiotica metabolism of the mammalian organism, the liver) are very low to undetectable. Quite likely other oxidative enzymes [e.g. flavin monooxygenase, COX (cooxidation by prostaglandin synthase)] will turn out to be much more important for the oxidative xenobiotic metabolism in the skin. Moreover, conjugating enzyme activities such as glutathione transferases and glucuronosyltransferases are much higher than the oxidative CYP activities. Since these conjugating enzymes are predominantly detoxifying, the skin appears to be predominantly protected against CYP-generated reactive metabolites. The following recommendations for the use of experimental animal species or human skin in vitro models may tentatively be derived from the information available to date: for dermal absorption and for skin irritation esterase activity is of special importance which in pig skin, some human cell lines and reconstructed skin models appears reasonably close to native human skin. With respect to genotoxicity and sensitization reactive-metabolite-reducing XME in primary human keratinocytes and several reconstructed human skin models appear reasonably close to human skin. For a more detailed delineation and discussion of the severe limitations see the Conclusions section in the end of this review.

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Section: Xenobiotica-metabolizing Enzymes In the Mouse Skinmentioning

confidence: 99%

“…Dwivedi et al (2013) reported measurable GST activities with CDNB as substrate in Swiss Albino female mice skin (140 ± 34 nmol/min/mg S9 protein).…”

Section: Xenobiotica-metabolizing Enzymes In the Mouse Skinmentioning

confidence: 99%

Xenobiotica-metabolizing enzymes in the skin of rat, mouse, pig, guinea pig, man, and in human skin models

2018

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“…This might be a consequence of its chemical structure, since it contains transitional met als known to induce ROS formation through the Fenton reaction (Calviello et al, 2006). Ascorbic acid (vita min C) represents the most important antioxidant in ex tracellular fluids (Dwivedi et al, 2013). This water solu ble vitamin has the ability to trap radicals in the aqueous phase and protect biomembranes from peroxidative damage (Eroglu et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

The Effect of Ascorbic Acid on Mancozeb-Induced Toxicity in Rat Thymocytes

Pavlovic,

Cekic,

Kamenov

et al. 2015

Fol. Biol.

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Mancozeb, as a dithiocarbamate fungicide, has been found to exhibit toxicological manifestations in different cells, mainly by generation of free radicals which may alter antioxidant defence systems in cells. The effect of mancozeb on the cells of a primary lymphoid organ has not been studied. In the present study, the effects of mancozeb (0.2, 2 and 5 μg/ml) or mancozeb+ascorbic acid (100 μg/ml), or ascorbic acid alone or control medium alone on the levels of cell viability, apoptosis, intracellular reactive oxygen species production (ROS), mitochondrial membrane potential (MMP) and ATP levels in rat thymocytes were examined in vitro. Cells treated with mancozeb displayed a concentration-dependent increase of hypodiploid cells and ROS production followed by markedly decreased viability of the cells, MMP and ATP levels. Application of ascorbic acid significantly reduced cytotoxicity in cell cultures treated with 0.2 and 2 μg/ml of mancozeb, together with significantly decreased ROS levels and increased MMP and ATP levels. In cells treated with 5 μg/ml of mancozeb, ascorbic acid failed to reduce toxicity while simultaneously increasing the apoptosis rate of thymocytes. These results suggest that ROS plays a significant role in mancozeb-induced toxicity, through alteration of mitochondrial function. Ascorbic acid administration reduced the toxicity rate in cells treated with lower mancozeb concentrations, while it may have the ability to shift cells from necrosis to apoptosis in the presence of highest mancozeb concentrations.

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