Improvement of hydrogen production by reduction of the photosynthetic oxygen in microalgae cultures of Chlamydomonas gloeopara and Scenedesmus obliquus

Age-related macular degeneration (AMD) is a degenerative disorder of the central retina and is the leading cause of irreversible central vision loss in elderly populations in developed countries, affecting 30 to 50 million people worldwide. Age-related macular degeneration is classified into early and late stages. Severe visual loss is usually associated only with the advanced (late) forms of the disease: geographic atrophy (GA) and choroidal neovascularization.1

Geographic atrophy is characterized by scattered or confluent areas of degeneration of RPE cells and the overlying photoreceptors, which rely on the RPE for trophic support. Currently, the mechanism and pathogenesis of GA are still unclear, and no treatment currently exists for GA. Oxidative stress, together with advanced age, smoking, and genetic factors, are considered major contributors to AMD development.2,3 The retina is particularly vulnerable to oxidative damage because of its intensive oxygen metabolism, continual exposure to light, high concentrations of polyunsaturated fatty acids, and the presence of photosensitizers, which increase the production of reactive oxygen species (ROS) in the retina.4,5 An overload of ROS can lead to RPE cell death and chronic inflammation, which can lead to a pathological immune response in AMD. Consistent with involvement of oxidative stress in dry AMD, the Age-Related Eye Disease Study (AREDS) formulation, which contains vitamins and zinc, has been shown to slow AMD progression.2

Currently, RPE cell death in AMD is mostly attributed to apoptosis,6 although there is some evidence from in vitro and in vivo studies supporting a necrotic nature of RPE cell death.7,8 By performing detailed morphological, biochemical, and molecular studies, we recently showed that necrosis is a major mechanism of RPE cell death in response to oxidative stress.9 The inflammatory nature of necrosis is consistent with the significant involvement of inflammation in AMD pathogenesis.

Cells have developed a complex system to protect them against oxidative stress. Initial exposure activates a battery of defensive genes that leads to both the detoxification of chemicals and ROS and the prevention of free radical generation so as to promote cell survival. The nuclear factor E2-related factor 2 (NRF2) pathway is a key cellular defense mechanism to combat oxidative stress. The NRF2 is a transcription factor and master regulator of many antioxidant/detoxification genes, including phase 2 antioxidant enzymes.10 The NRF2 functions by binding to a cis-acting element known as the antioxidant response element (ARE), and regulates expression and induction of antioxidant enzyme genes in response to a variety of stimuli, including oxidants, xenobiotics, metals, and UV irradiation.11,12 The RPE of older mice demonstrated impaired induction of the NRF2 pathway following oxidative stress induced with sodium iodate, indicating that the aging RPE is vulnerable to oxidative damage due to impaired NRF2 signaling and that the NRF2 pathway may play an important role in AMD pathogenesis.13

Hydroquinone derivatives have established antioxidant properties characterized by different dynamic of NRF2 induction and have been shown to activate phase 2 enzymes.14,15

Hydroquinone has the ability to induce HO-1 expression,16 whereas its derivatives, like quinone, quercetin, kaempferol, or tert-butylhydroquinone, activate HO-1 and NQO1 expression.17–19

A hydroquinone derivative, 4-Acetoxyphenol (4-AC), has been shown to be a potent activator of the NRF2-ARE pathway in motor neurons.20 It was also identified as an α-synuclein modulator that can possibly prevent or slow down the onset or progression of Parkinson's disease.21

We have identified several natural compounds approved by the US Food and Drug Administration (FDA) that protect oxidative stress–induced RPE death from a chemical library screening.22 Here we provide a detailed study on one of the top candidates, 4-AC. We found that 4-AC, a hydroquinone derivative, has potent antioxidation capability. It protects ARPE-19 cells from oxidative stress–induced necrosis by blocking an increase of intracellular ROS induced by oxidative stress through regulation of antioxidative genes NQO1 and HO-1. Mechanistically, 4-AC induces NRF2 stabilization and nuclear translocation; and NRF2 is required for 4-AC function in preventing RPE cells from oxidative stress–induced necrosis.

4-Acetoxyphenol Prevents RPE Oxidative Stress-Induced Necrosis by Functioning as an NRF2 Stabilizer.

The invention provides a quercetin hydrocarbylation derivative which is characterized in that in a general formula (1), R1, R2, R3 and R4 are respectively and independently selected from H, (CH2)3CH3, CH2CH=CHPh, CH2CH=CH(CH3)CH3, and CH2CH=CH(CH3)CH2CH2CH=CH(CH3)CH3, and the R1, the R2, the R3 and the R4 are not all Hs.

Quercetin hydrocarbylation derivative and preparation method and application thereof

Theoretical and experimental investigation on the electrochemical properties, structural and spectroscopic parameters of 6,7-dihydroxy-9-thia-1,4a-diaza fluoren-2-one (DTDFO)

1.

A new method is proposed for increasing the antioxidant efficiency of chemical compounds of the hydroquinone class by aminomethylation. Four Mannich base derivatives of hydroquinone were synthesized by this method.




2.

The relative antioxidant efficiency of the compounds synthesized was assessed by an accelerated kinetic method. All the hydroquinone derivatives investigated had a high antioxidant activity in the oxidation of methyl oleate.

The antioxidant efficiency of some hydroquinone derivatives

1.

7-Alkyl (butyl, pentyl, and isopentyl) ethers of quercetin were synethesized.




2.

It was shown that the compounds synthesized have high antioxidant efficiency with respect to methyl oleate and to solutions of vitamin A acetate in soybean oil.

7-alkyl ethers of quercetin and their antioxidant efficiency

The formation of OH radicals in the photoreduction of aqueous solutions of anthraquinonesulfonic acid as the result of electron transfer from water (OH−) to a triplet molecule has been demonstrated.

Photochemical reduction of organic electron acceptors in aqueous solutions

1.

Some 2-alkyl-6-methyl-3-pyridinols were synthesized by the reaction of 2-acyl-5-methylfurans with ammonia.




2.

A study was made of the antioxidative effectiveness of some 2,6-dialkyl-3-pyridinols for the oxidation of methyl oleate.




3.

The most effective antioxidant was 2-ethyl-6-methyl-3-pyridinol.




4.

The introduction of a dimethylaminomethyl, piperidinomethyl, or morpholinomethyl group in the 4 position of a 2,6-dialkyl-3-pyridinol molecule practically destroys the antioxidant properties of the substance.

S. I. Sholina

Papers

The antioxidant efficiency of some hydroquinone derivatives

7-alkyl ethers of quercetin and their antioxidant efficiency

Photochemical reduction of organic electron acceptors in aqueous solutions

Sterically hindered 3-pyridinols