Oxidative stress–mediated photoactivation of carbazole inhibits human skin cell physiology

Abstract

Prolonged exposure of the earth's surface to the sun's ultraviolet radiation may result in various skin diseases and cataract. Carbazole (CBZ), as a polycyclic‐aromatic hydrocarbon (PAH), is blended with a five‐member nitrogen‐containing ring. It is found in cigarette smoke, coal, eye kohl, tattoo ink, and wood combustion and affects various types of flora and fauna. Our findings suggest that CBZ generates reactive oxygen species (ROS) like O2•− through type‐I photodynamic reaction and causes phototoxicity in the human keratinocyte cell line (HaCaT), which has been proved by mitochondrial dehydrogenase and neutral red uptake assays. CBZ induces single strand DNA damage. We have investigated the involvement of the apoptotic pattern of cell death and confirmed it by cytochrome C release from mitochondria and caspase‐9 activation. Similarly, photo‐micronuclei formation was associated to CBZ‐induced phototoxicity. The results of this study strongly support that the upregulation of bax, cyto‐C, apaf‐1, casp‐9 and down regulation of bcl2, keap‐1, nrf‐2, and hmox‐1 genes cause apoptopic cell death. Downregulation of antioxidant genes showed a significant amount of ROS generation by photosensitized CBZ. Therefore, the current study will be a step forward to safeguard human beings from sunlight‐induced photosensitive CBZ prolonged exposure.

The effect of a color tattoo on the local skin redox regulatory network: an N-of-1 study

“…Nevertheless, oxidative stress has been proposed as the most important pathophysiological mediator responsible for tattoo-related health complaints such as swelling, itching and redness following solar radiation exposure in the famous "Beach study" (Hutton Carlsen and Serup 2014). Interestingly, association of reactive oxygen species (ROS) and tattoo ink in humans has so far only been supported by indirect findings from in vitro toxicological studies (Høgsberg et al 2013;Neale et al 2015) and theoretical assumptions based on the fact that mechanisms of photoactivation underlying the biological effects of photodynamic therapy were also shown for some chemicals that are often present in tattoo inks such as polycyclic aromatic hydrocarbons (Hutton Carlsen and Serup 2014;Srivastav et al 2020). Nevertheless, PubMed search for "tattoo" AND "oxidative stress" and "tattoo" AND "ROS" only yield 7 and 8 hits respectively, and none of the results provide any evidence for direct oxidative stress effects of tattooing in humans.…”

The Effect of a Color Tattoo on the Local Skin Redox Regulatory Network: An N-of-1 Study

“…Nevertheless, oxidative stress has been proposed as the most important pathophysiological mediator responsible for tattoo-related health complaints such as swelling, itching and redness following solar radiation exposure in the famous "Beach study" (Hutton Carlsen and Serup 2014). Interestingly, association of reactive oxygen species (ROS) and tattoo ink in humans has so far only been supported by indirect findings from in vitro toxicological studies (Høgsberg et al 2013;Neale et al 2015) and theoretical assumptions based on the fact that mechanisms of photoactivation underlying the biological effects of photodynamic therapy were also shown for some chemicals that are often present in tattoo inks such as polycyclic aromatic hydrocarbons (Hutton Carlsen and Serup 2014; Srivastav et al 2020). Nevertheless, PubMed search for "tattoo" AND "oxidative stress" and "tattoo" AND "ROS" only yield 7 and 8 hits respectively, and none of the results provide any evidence for direct oxidative stress effects of tattooing in humans.…”

Targeting autophagy to overcome drug resistance: further developments

“…CQ stimulates a slow protein accumulation, localized to lysosomes, while bortezomib induces a rapid buildup of proteins where aggresome formation is in the cytosol [141]. The accumulation events often lead to mitochondrial disorder, accompanied by the release of cytochrome c and the activation of Apaf-1 containing apoptotic complex [142]. Thus, the combination of proteasome inhibition with autophagy inhibition can achieve stronger antitumor effect.…”