Phototoxicity of Kava — Formation of Reactive Oxygen Species Leading to Lipid Peroxidation and DNA Damage

Abstract

Kava is one of the most widely sold herbal dietary supplements in the United States. It has been reported that, besides exhibiting hepatotoxicity, kava also possesses photosensitivity and induces dermopathy in humans. In this study, we determined that UVA irradiation of kava in the presence of a lipid, methyl linoleate, generated lipid peroxidation which was mediated by singlet oxygen generated during photoirradiation. The six major kavalactones (yangonin, 7,8-dihydrokawa in, kawain, 7,8-dihydromethysticin, methysticin, and 5,6-dehydrokawain) were also studied in parallel; only 5,6-dehydrokawain and yangonin-induced a low level of lipid peroxidation. UVA irradiation of kava in human HaCaT skin keratinocytes induced cytotoxicity which was mediated by oxidative stress, led to DNA strand cleavage, and produced 8-hydroxy-2′-deoxyguanosine (8-OHdG) adduct. Study by the electron spin resonance (ESR) method revealed that UVA irradiation of kava produced singlet oxygen and carbon-centered radicals. The overall results suggest that kava is photocytotoxic and photogenotoxic, both mediated by free radicals generated during photoirradiation.

Reduced Disc Shedding and Phagocytosis of Photoreceptor Outer Segment Contributes to Kava Kava Extract–induced Retinal Degeneration in F344/N Rats

“…It has also been reported that kava possesses phototoxicity mediated by free radicals under UVA light (Xia et al 2012). Wavelength in the UVA band has little propagation into the eye beyond the lens; therefore, only drugs or chemicals with significant visible (VIS) wavelength absorption represent a likely phototoxic risk to the retina.…”

Nanotoxicology: A Review

“…Oxidative stress is referred to as an imbalance between the production of reactive oxygen species (ROS) and the cells' ability to reduce ROS, which may be as a result an increased ROS production, a decrease in the cell's defense mechanisms, or a combination of both [40]. An overproduction of ROS may induce oxidative stress, resulting in cells failing to maintain normal physiological redox-regulated functions further resulting in oxidative modification of proteins to generate protein radicals [41], initiation of lipid peroxidation [42], DNA strand breaks and modification to nucleic acids [43], modulation of gene expression [44], thereby leading to cell death and genotoxic effects [45]. To minimize the effects of ROS-oxidative damage to cellular components, biological systems have developed a complex antioxidant system, comprised of both enzymatic and non-enzymatic defense mechanisms.…”

Therapeutic Potential of Neem Synthesized Silver Nanoparticles on Human Gastric Cancer Cells <i>in Vitro</i>

“…Much of the evidence (Figure 13) shows that antioxidants scavenge free radicals directly, or interfere with the generation of free radicals-mediated events, inhibit the neoplastic process [132]- [135]. Overproduction of ROS can induce oxidative stress, resulting in DNA-strand breaks, modification to nucleic acids [49] [63], modulation of gene expression through activation of redox-sensitive transcription factors [64] [65], and modulation of inflammatory responses through signal transduction [66], leading to cell death and genotoxic effects [67] [69].…”