Strand scission in DNA induced by quercetin and Cu(II): role of Cu(I) and oxygen free radicals

The naturally occurring flavonoid, quercetin, in the presenceof Cu(II) and molecular oxygen caused breakage of calf thymusDNA, supercolled pBR322 plasmid DNA and single-stranded M13phage DNA. In the case of the plasmid, the product(s) were relaxedcircles or a mixture of these and linear molecules dependingupon the conditions. For the breakage reaction, Cu(II) couldbe replaced by Fe(III) but not by other ions tested [Fe(II),Co(II), Ni(II), Mn(II) and Ca(II)]. Structurally related flavonoids,rutin, galangin, apigenin and fisetin, were ineffective or lesseffective than quercetin in causing DNA breakage. In the caseof the quercetln-Cu(II) reaction, Cu(I) was shown to be an essentialintermediate by using the Cu(I)-sequestering reagents, neocuproineand batho cuproine. By using Job plots we established that,in the absence of DNA, five Cu(II) ions can be reduced by onequercetin molecule; in contrast, two ions were reduced per quercetinmolecule in the DNA breakage reaction. Equally neocuproine inhibitedthe DNA breakage reaction. The involvement of active oxygenin the reaction was established by the inhibition of DNA breakageby superoxide dismutase, iodide, mannitol, formate and catalase(the inhibition was complete in the last case). From these datawe propose a mechanism for the DNA strand scisslon reactionof quercetin and related fiavonoids.     

Regression of left ventricular hypertrophy in a transplanted heart

A woman with advanced coronary artery disease underwent heart transplantation. The donor heart had left ventricular hypertrophy. The electrocardiographic and echocardiographic evidence of left ventricular hypertrophy regressed during follow up; estimated left ventricular mass decreased from 393 g to 171 g. The adaptation of myocardial mass and performance after transplantation is not fully understood. This case illustrates the potential for regression of left ventricular hypertrophy in response to altered loading conditions.     

Prazosin blunts the antinatriuretic effect of circulating angiotensin II in man.

OBJECTIVE: The present study examines the role of alpha 1-adrenoceptors in determining the renal haemodynamic and sodium excretory responses to a physiological dose of angiotensin II in man. DESIGN: The effects of a low-dose infusion of angiotensin II (1 ng/kg per min) and a non-depressor dose of prazosin (0.25 mg), alone and in combination, on urinary sodium excretion (UNaV), effective renal plasma flow (ERPF), glomerular filtration rate (GFR) and segmental tubular function were studied in eight normal male subjects. METHODS: Subjects were studied undergoing maximal water diuresis. Clearances of inulin and para-aminohippurate were employed to estimate GFR and ERPF, respectively. Segmental tubular handling was assessed by both lithium clearance (CLi) and solute-free water methods. RESULTS: Angiotensin II decreased UNaV without altering ERPF and GFR. Angiotensin II caused a significant fall in fractional CLi, which may indicate a proximal tubular effect of angiotensin II. Angiotensin II alone also increased fractional reabsorption of sodium delivered to the distal nephron, as evaluated by both the CLi method and by estimation of solute-free water clearance. When angiotensin II was given in combination with prazosin, which on its own had no apparent effects on any renal parameters, the antinatriuretic and tubular effects of angiotensin II were significantly blunted. CONCLUSIONS: These findings suggest that low doses of circulating angiotensin II are able to modulate UNaV by increasing sodium reabsorption in the proximal and, to some extent, the distal nephron segment in man. The study also showed that a non-depressor dose of prazosin blunted the renal effects of angiotensin II, thereby providing tentative evidence of a renal interaction between alpha-adrenoceptors and angiotensin II in man.