Silymarin in Combination with Vitamin C, Vitamin E, Coenzyme Q10 and Selenomethionine to Improve Liver Enzymes and Blood Lipid Profile in NAFLD Patients.

Background and Objectives: Non-Alcoholic Fatty Liver Disease (NAFLD) is an emerging cause of hepatopathy that is showing an increasing trend and where the recommendations of lifestyle modification are often not sufficient. The aim of this study is to evaluate the efficacy and tolerability profile of the association of silymarin, vitamin C, vitamin E, coenzyme Q10 and selenomethionine (Medronys epato®) by analyzing liver enzymes, along with the lipidic profile, as markers of liver function, and ultrasound results in NAFLD patients. Materials and Methods: This study enrolled 81 patients with mild to severe NAFLD, divided into two groups: Group A (N = 41) received two capsules a day of silymarin, vitamin C, vitamin E, coenzyme Q10 and selenomethionine (Medronys epato®), and Group B (N = 40) received only recommendations for lifestyle modification including hypocaloric diet, physical exercise and encouragement for weight loss. Patients have been evaluated at three timepoints: baseline (T0), after 45 days of treatment (T1) and after 90 days of treatment (T2), by collecting blood parameters of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) and the lipid blood profile. Ultrasonographic results have been analyzed at T0 and T2, along with the tolerability profile and side effects, registered at time T2. Results: The administration of the association of silymarin, vitamin C, vitamin E, coenzyme Q10 and selenomethionine (Medronys epato®) was effective since it showed a significant reduction of the evaluated parameters of ALT, AST, ALP and GGT, a significant improvement of lipid parameters, evaluated as markers of liver function, and improvements of ultrasonographic results. The use of this formulation at the dosage of two capsules a day has been well tolerated and no adverse events have been reported during study period of three months. Conclusions: The administration of the association of silymarin, vitamin C, vitamin E, coenzyme Q10 and selenomethionine (Medronys epato®) was effective and well tolerated in the improvement of hepatic function of NAFLD patients.

Electron Transfer Reactions: KO tBu (but not NaO tBu) Photoreduces Benzophenone under Activation by Visible Light.

Long-standing controversial reports of electron transfer from KO tBu to benzophenone have been investigated and resolved. The mismatch in the oxidation potential of KO tBu (+0.10 V vs SCE in DMF) and the first reduction potential of benzophenone (of many values cited in the literature, the least negative value is -1.31 V vs SCE in DMF), preclude direct electron transfer. Experimental and computational results now establish that a complex is formed between the two reagents, with the potassium ion providing the linkage, which markedly shifts the absorption spectrum to provide a tail in the visible light region. Photoactivation at room temperature by irradiation at defined wavelength (365 or 400 nm), or even by winter daylight, leads to the development of the blue color of the potassium salt of benzophenone ketyl, whereas no reaction is observed when the reaction mixture is maintained in darkness. So, no electron transfer occurs in the ground state. However, when photoexcited, electron transfer occurs within a complex formed from benzophenone and KO tBu. TDDFT studies match experimental findings and also define the electronic transition within the complex as n → π*, originating on the butoxide oxygen. Computation and experiment also align in showing that this reaction is selective for KO tBu; no such effect occurs with NaO tBu, providing the first case where such alkali metal ion selectivity is rationalized in detail. Chemical evidence is provided for the photoactivated electron transfer from KO tBu to benzophenone: tert-butoxyl radicals are formed and undergo fragmentation to form (acetone and) methyl radicals, some of which are trapped by benzophenone. Likewise, when KOC(Et)3 is used in place of KO tBu, then ethylation of benzophenone is seen. Further evidence of electron transfer was seen when the reaction was conducted in benzene, in the presence of p-iodotoluene; this triggered BHAS coupling to form 4-methylbiphenyl in 74% yield.

Dual Roles for Potassium Hydride in Haloarene Reduction: CSNAr and Single Electron Transfer Reduction via Organic Electron Donors Formed in Benzene.

Potassium hydride behaves uniquely and differently than sodium hydride toward aryl halides. Its reactions with a range of haloarenes, including designed 2,6-dialkylhaloarenes, were studied in THF and in benzene. In THF, evidence supports concerted nucleophilic aromatic substitution, CSNAr, and the mechanism originally proposed by Pierre et al. is now validated through DFT studies. In benzene, besides this pathway, strong evidence for single electron transfer chemistry is reported. Experimental observations and DFT studies lead us to propose organic super electron donor generation to initiate BHAS (base-promoted homolytic aromatic substitution) cycles. Organic donor formation originates from deprotonation of benzene by KH; attack on benzene by the resulting phenylpotassium generates phenylcyclohexadienylpotassium that can undergo (i) deprotonation to form an organic super electron donor or (ii) hydride loss to afford biphenyl. Until now, BHAS reactions have been triggered by reaction of a base, MO tBu (M = K, Na), with many different types of organic additive, all containing heteroatoms (N or O or S) that enhance their acidity and place them within range of MO tBu as a base. This paper shows that with the stronger base, KH, even a hydrocarbon (benzene) can be converted into an electron-donating initiator.

KOtBu: A Privileged Reagent for Electron Transfer Reactions?

Many recent studies have used KOtBu in organic reactions that involve single electron transfer; in the literature, the electron transfer is proposed to occur either directly from the metal alkoxide or indirectly, following reaction of the alkoxide with a solvent or additive. These reaction classes include coupling reactions of halobenzenes and arenes, reductive cleavages of dithianes, and SRN1 reactions. Direct electron transfer would imply that alkali metal alkoxides are willing partners in these electron transfer reactions, but the literature reports provide little or no experimental evidence for this. This paper examines each of these classes of reaction in turn, and contests the roles proposed for KOtBu; instead, it provides new mechanistic information that in each case supports the in situ formation of organic electron donors. We go on to show that direct electron transfer from KOtBu can however occur in appropriate cases, where the electron acceptor has a reduction potential near the oxidation potential of KOtBu, and the example that we use is CBr4. In this case, computational results support electrochemical data in backing a direct electron transfer reaction.