Mechanisms of hepatocellular toxicity associated with the components of St. John's Wort extract hypericin and hyperforin in HepG2 and HepaRG cells.

St. John's Wort preparations are used for the treatment of mild to moderate depression. They are usually well tolerated but can cause adverse reactions including liver toxicity in rare cases. To date, the mechanism(s) underlying the hepatotoxicity of St. John's Wort extracts are poorly investigated. We studied the hepatocellular toxicity of hypericin and hyperforin as the two main ingredients of St. John's Wort extracts in HepG2 and HepaRG cells and compared the effects to citalopram (a synthetic serotonin uptake inhibitor) with a special focus on mitochondrial toxicity and oxidative stress. In HepG2 cells, hypericin was membrane-toxic at 100 µM and depleted ATP at 20 µM. In HepaRG cells, ATP depletion started at 5 µM. In comparison, hyperforin and citalopram were not toxic up to 100 µM. In HepG2 cells, hypericin decreased maximal respiration starting at 2 µM and mitochondrial ATP formation starting at 10 µM but did not affect glycolytic ATP production. Hypericin inhibited the activity of complex I, II and IV of the electron transfer system and caused mitochondrial superoxide accumulation in cells. The protein expression of mitochondrial superoxide dismutase 2 (SOD2) and thioredoxin 2 (TRX2) and total and reduced glutathione decreased in cells exposed to hypericin. Finally, hypericin diminished the mitochondrial DNA copy number and caused cell necrosis but not apoptosis. In conclusion, hypericin, but not hyperforin or citalopram, is a mitochondrial toxicant at low micromolar concentrations. This mechanism may contribute to the hepatotoxicity occasionally observed in susceptible patients treated with St. John's Wort preparations.

Backside light management of 4-terminal bifacial perovskite/silicon tandem PV modules evaluated under realistic conditions.

Perovskite/silicon tandem modules have recently attracted growing interest as a potential candidate for new generations of solar modules. Combined with a bifacial configuration it can lead to considerable energy yield improvement in comparison to conventional monofacial tandem solar modules. Optical modeling is crucial to analyze the optical losses of perovskite/silicon solar modules and achieve efficient light management. In this article we study the optical properties of four-terminal bifacial tandem modules, using metal-halide perovskite top solar cell and a conventional industrial crystalline silicon PERC bottom solar cell. We propose a method to analyze bifacial gains, improve back side light management and challenge it under realistic spectral conditions at several locations with various albedos. We show that both optimized designs for the back side show comparable advantages at all locations. These results are a good sign for the standardization of bifacial four-terminal perovskite/silicon modules.