Disease relevance of Dihydrothioctic acid

• Dihydrolipoate reduces neuronal injury after cerebral ischemia [1].
• Dihydrolipoate treatment (50 and 100 mg/kg) could not ameliorate neuronal damage in the rat hippocampus or cortex caused by 10 min of forebrain ischemia [1].
• In vivo, dihydrolipoate treatment (50 and 100 mg/kg) reduced brain infarction after permanent middle cerebral artery occlusion in mice and rats [1].
• Unlike these enzymes, thioredoxin from E. coli exhibited no stereoselectivity upon reduction with chemically obtained dihydrolipoate [2].
• Dihydrolipoate, if added into the perfusion buffer at 0.3 microM concentration, keeps the pH higher (7. 15) during hypoxia as compared to controls (6.98) [3].

High impact information on Dihydrothioctic acid

• Glutathione, mercaptoethanol, and dihydrolipoate support the hydroxylation of phenylalanine essentially as well as DTT [4].
• NF-kappa B activation that is induced by either calyculin A or okadaic acid (inhibitors of serine/threonine protein phosphatases 1 and 2A) is not blocked by N-acetylcysteine or dihydrolipoate in Jurkat and U937 cells [5].
• It has been shown in vitro that dihydrolipoate (DL-6,8-dithioloctanoic acid) has antioxidant activity against microsomal lipid peroxidation [1].
• In vitro, conjugate formation could be inhibited by the dithiol dihydrolipoate but not by its oxidised form, lipoic acid [6].
• Under conditions of reductive stress, alpha-lipoate decreases high NADH levels in the cell by utilizing it as a co-factor for its own reduction process, whereas in oxidative stress both alpha-lipoate and its reduced form, dihydrolipoate, may protect by direct scavenging of free radicals and recycling other antioxidants from their oxidized forms [7].

Chemical compound and disease context of Dihydrothioctic acid

• Lipoate/dihydrolipoate effectively reduced reperfusion injury in isolated working rat hearts and in exarticulated rat hind limbs after extended ischemia [8].

Biological context of Dihydrothioctic acid

• In contrast, dihydrolipoate and its disulfide lipoate protected the plasmid DNA [9].

Anatomical context of Dihydrothioctic acid

• Our results indicate that a transport system exists for alpha-lipoic acid and dihydrolipoate; resealed erythrocyte ghosts, containing trapped lipoamide dehydrogenase and pyridine nucleotides, reduced externally added lipoate [10].
• The aged mitochondria were able to catalyze the exchange of [14C]-bicarbonate-glycine and the oxidation of dihydrolipoate, indicating the persistence of P-, H-, and L-protein activities [11].
• The protection by GSH, but not dihydrolipoate or dithioerythritol, appeared to be enzymic since it was lost after microsomes were heated or treated with trypsin [12].
• However, during incubation with adipocytes, alpha-lipoate, and dihydrolipoate promoted the decline in immunoreactive insulin nearly equally [13].
• The stimulation of the mitochondrial permeability transition (MPT) by dihydrolipoate (DHLA) was studied in rat liver mitochondria in the presence of different respiratory substrates [14].

Associations of Dihydrothioctic acid with other chemical compounds

• Normal human erythrocytes reduced lipoate to dihydrolipoate only in the presence of glucose; deoxyglucose did not substitute for glucose, indicating that the reduction of lipoate requires glucose metabolism [10].
• The requirement of NADH and NADPH as cofactors in the cellular reduction of alpha-lipoic acid to dihydrolipoate has been reported in various cells and tissues [7].
• The reverse reaction, i.e., production of glycine from serine, ammonium, dihydrolipoate, and bicarbonate, was also inhibited in these aged mitochondria [11].
• The oxidation of the antioxidants dihydrolipoate and lipoamide by triplet duroquinone (3DQ) has been studied by laser flash photolysis and time-resolved resonance Raman (TR3) spectroscopy [15].
• Both substances promoted the permeability transition in isolated rat liver mitochondria and in permeabilized hepatocytes, dihydrolipoate most potently in spite of it being a dithiol [16].

Gene context of Dihydrothioctic acid

• These results indicated the involvement of the third complex component, dihydrolipoyl dehydrogenase, in the 2-oxoacid-dependent dihydrolipoate formation [2].
• Dihydrolipoate is a potent radical scavenger, and may provide significant antioxidant protection [10].
• Change in alpha-ketoglutarate dehydrogenase cooperative properties due to dihydrolipoate and NADH [17].
• Concomitantly, thioredoxin stimulates the complex-bound dihydrolipoate-dependent production of reactive oxygen species [18].
• When BSA (1 mM) was incubated with 500 mM glucose in the presence of alpha-lipoate homologues or dihydrolipoate (6,8-dimercaptooctanoate, DHLA) at 37 degrees C for 72 h, both alpha-lipoate (racemic, R- and S-forms) and DHLA inhibited BSA glycation similarly, but tetranorlipoate (1,2-dithiolane-3-carboxylate) did not [19].

Analytical, diagnostic and therapeutic context of Dihydrothioctic acid

• The dihydrolipoate group contained 8.3 microM in the modified reperfusate (controlled reperfusion) [3].
• Weights were measured every 3 days and venous blood obtained every 5 weeks for CBC; serum biochemical analyses; lymphocyte blastogenesis; thiobarbituric acid reactive substances concentration; and concentrations of plasma protein carbonyl, 8-OH d-guanosine, blood glutathione, plasma amino acid, lipoate, and dihydrolipoate [20].
• The addition of spin trapping nitrones N-tert-butyl-Alpha-phenyl-nitrone (PBN) or its sulfonated analog N-tert-butyl-Alpha(2-sulfophenyl)-nitrone (SPBN) to the pre-treatment cocktail enhanced neuroprotection at every dihydrolipoate concentration [21].

References