Protective effects of foods rich in carotenoids against DNA damages due to reactions of chemically induced triplet states of melanin derivatives
Final Report Abstract
UV-exposure is a major risk factor for skin cancer with photochemically induced DNA damage as the underlying mechanism. Dietary intake of compounds with photoprotective properties is suggested as additional protection to the use of topical sunscreens. Carotenoids and flavonoids are such photoprotective agents. Pure compounds and plant extracts rich in these carotenoids were investigated in the present study with focus on the prevention of delayed DNA damage due the delayed formation of so called „dark dimers“. In context with the study, analytical methods for the determination of carotenoids and flavonoids in cells and plant extracts were established and the compounds were isolated from the plant extracts. Further analytical and biochemical methods were developed to measure biomarkers of UV-induced damage in model systems and cell culture in order to evaluate light-protective properties of dietary constituents. In addition to lycopene, β-carotene and lutein, the flavonoids luteolin, tricetin, nobiletin and tangeretin were investigated. Especially tricetin and luteolin proved to be efficient photoprotectants as shown in normal and artificially aged skin cells (fibroblasts). The basal effects of UV-irradiation on aged fibroblasts were further investigated. Upon UV-stress, aged cells showed an increase in cellular respiration along with an increase in ROS formation and a lower sensitivity towards UV-dependent damage, as compared to non-aged control cells. Several methods based on HPLC-MS/MS analyses, immunochemistry or specific enzymatic cleavage were established for the determination of UV-induced dark dimers. With the latter, no protective effects of carotenoids on „dark dimer“ formation was found. Here more sensitive analyses such as improved HPLC-MS/MS are required. It was observed that upon low-dose UV-irradiation, fibroblast show a strong increase in the expression of the enzyme hemeoxygenase-1. In context with the effects of UV light on cellular respiration, we investigated the implication of hemeoxygenase-1 as a source for the signalling molecule CO (carbon monoxide). We showed that the exposure of cells towards CO- generating compounds (CORMs) provoke CO-typical responses like inhibition of the respiratory chain and compensation via increased glycolysis. Interestingly, we demonstrated an additional short term effect of CO which comprises a transient shift in glucose utilization from glycolysis to the pentose phosphate pathway. This is likely to compensate for NADPH-dependent metabolic demands under stress conditions and thus related to UV-exposure. The present data show that dietary constituents contribute to photoprotection, however, the analysis of different biomarkers is required to establish underlying mechanisms of protection.
Publications
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(2019) Carbon monoxide releasing molecule 401 (CORM-401) modulates phase I metabolism of xenobiotics. Toxicol in Vitro. 59: 215
Walter M, Stahl W, Brenneisen P, Reichert AS, Stucki D
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(2020) Bioavailability of naringenin chalcone in humans after ingestion of cherry tomatoes. Int J Vitam Nutr Res. 90: 411
Kolot C, Rodriguez-Mateos A, Feliciano R, Bottermann K, Stahl W
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(2020) Carbon monoxide - beyond toxicity? Toxicol Let 333: 251
Stucki D, Stahl W
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(2020) Carotenoids in human skin. BBA 1865: 158588
Zerres S, Stahl W
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(2020) Effects of frequently applied carbon monoxide releasing molecules (CORMs) in typical CO-sensitive model systems – A comparative in vitro study. ABB 687:108383
Stucki D, Krahl H, Walter M, Steinhausen J, Hommel K, Brenneisen P & Stahl W
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(2020) Endogenous carbon monoxide signaling modulates mitochondrial function and intracellular glucose utilization: impact of the heme oxygenase substrate hemin. Antioxidants 9: 652
Stucki D, Steinhausen J, Westhoff P, Krahl H, Brilhaus D, Massenberg A, Weber APM, Reichert AS, Brenneisen P, Stahl W
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(2021) Carbon monoxide exposure activates ULK1 via AMPK phosphorylation in murine embryonic fibroblasts. Int J Vitam Nutr Res.
Stucki D, Westhoff P, Brilhaus D, Weber APM, Brenneisen P, Stahl W
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(2021) Nutritional cognitive neuroscience of aging: focus on carotenoids and cognitive frailty. Redox Biol 44:101996
Polidori MC, Stahl W, Griffiths HR
