Effects of inorganic lead in vitro on ion exchanges and respiratory metabolism of rat kidney cortex

Abstract

The effects of Pb2+ added in vitro to tissue slices, isolated tubules and isolated mitochondria of rat kidney cortex have been studied. Slices were depleted of K+ and loaded with Na+, Cl- and water by pre-incubation at 1 degree C, and reversal of these changes was then induced by incubation under metabolically favourable conditions. The net reaccumulation of K+ was reduced by a maximum of 30% when Pb2+ was present in the medium, the maximal effect being caused by 200 microM Pb2+. Lead also caused a reduction of Na+ extrusion which was approximately equimolar with its effect on K+, but it did not affect the extrusion of Cl- and water. The initial rates of the net, active movements of K+ and Na+ were not altered by Pb2+, divergence from control values only being noted after 15-30 min incubation. The O2 consumption and the ATP content were 25-30% lower in slices incubated with 200 microM Pb2+ than in control slices; the effect on ATP content was not observed until incubation had continued for 30 min. In tubules isolated from the renal cortex, the rate of respiration (50%) and ATP content (30%) were also partly reduced by 200 microM Pb2+. The consumption of O2 by mitochondria isolated from the cortex was much more sensitive to Pb2+ added in vitro than the respiration of intact cells; the rate of respiration in state 3 (presence of phosphate acceptor) and the respiratory control ratio were drastically reduced, with half-maximal inhibition at 30 and 20 microM Pb2+ respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Mitochondrial Oxidative Stress Is the General Reason for Apoptosis Induced by Different-Valence Heavy Metals in Cells and Mitochondria

“…Ruthenium red, N 3 -, and La 3+ were previously shown to inhibit the uptake of Pb 2+ by isolated rat kidney mitochondria [60]. Ca 2+ uptake inhibition, ∆Ψ mito decline, a swelling and state 4 0 increase, a state 3 decrease, and a fast release of accumulated Ca 2+ were induced by Pb 2+ in experiments with RKM, which were energized by CI-CII substrates [61][62][63]. RR prevented the Pb 2+ -induced ∆Ψ mito decline, state 3 respiration decrease, and Ca 2+ release in RKM energized by succinate but not by NAD-dependent substrates [60,61].…”