Effects of lead, copper, and zinc on the rat's lactate dehydrogenase in vivo and in vitro

Abstract

Following subacute intoxication of rats with Pb-, Cu-, and Zn-salts (separately or in mixture) for 5 weeks, the chelating agent D-penicillamine was administered for 3 weeks. In the course of the 3-month experiment, lactate dehydrogenase (LDH) was estimated in serum and in cytoplasmic fraction of the kidney. Pb2+ treatment resulted in an increase of LDH activity, Cu2+ in a slight decrease, whereas Zn2+ had no effect, respectively. Mixture of these metals caused a significant rise in the enzymatic activity. Seven weeks after the stoppage of the administration of toxic substances, altered LDH activity, both in serum and in kidney returned to normal. D-penicillamine treatment was found to accelerate a restoration of the enzyme activity. In the experiments in vitro, Cu2+ inhibited significantly the kidney LDH activity, Pb2+ and Zn2+ being 100- and 400-times less efficient, respectively. Cu2+ inhibition was reversed by D-penicillamine, whereas inhibition of LDH by Zn2+ or Pb2+ was irreversible.

Screening of a composite library of clinically used drugs and well-characterized pharmacological compounds for cystathionine β-synthase inhibition identifies benserazide as a drug potentially suitable for repurposing for the experimental therapy of colon cancer

“…One side-finding of the current work was the "re-rediscovery" of the inhibitory effect of copper ions on CBS activity; a finding that has already been described in 1958 by Matsuo and Greenberg [36], and re-discovered by the Kraus group in 2005 [37]. Although the potency of copper was found to be remarkable -in fact, copper is technically the most potent CBS inhibitor "compound" known to date -free copper ions did not exert antiproliferative effects in HCT116 cells, probably due to limited cell uptake, as well as the high ability of cells to sequester and neutralize any free copper ions [73,74].…”

“…11, copper only inhibited HCT116 cells proliferation at the highest concentration tested (1 mM), which also decreased MTT conversion and LDH activity. The paradoxical reduction in LDH activity is most likely the result of the previously reported [37] direct inhibition of the LDH enzyme by copper ions. The major benserazide metabolite 2,3,4trihydroxybenzylhydrazine (THBH, also known as Ro 04-5127) also acted as a CBS inhibitor with potency comparable to benserazide (at 10, 30 and 100 M, it exerted a 31 ± 2%, 51 ± 2% and 82% inhibition of recombinant CBS activity, n = 3) and inhibited HCT116 cell proliferation in vitro at 10-300 M; it reduced MTT conversion at 300 M, but did not exert cytotoxic effects, as evidenced by a lack of significant increase of LDH concentrations in the cell culture medium (Fig.…”

Hematological and serum biochemical parameters of blood in adolescent rats and histomorphological changes in the jejunal epithelium and liver after chronic exposure to cadmium and lead in the case of supplementation with green tea vs black, red or white tea

“…On the other hand, kidneys of leadpoisoned guinea pigs showed ischemia and a significant increase in LDH activity under the effect of Pb, which can be considered as an expression of metabolic adjustment of the tissue to cellular hypoxia due to reduced activity of the Krebs cycle. Moreover, Pb is known to influence the permeability of the cellular membrane; therefore, an additional amount of the enzyme may be released into the bloodstream (Dobryszczycka and Owczarek, 1981).…”

Biomarkers responses in muscle of Senegal sole (Solea senegalensis) from a heavy metals and PAHs polluted estuary

“…On prolonged exposure zinc-exposed fish could adapt to sublethal toxic stress. Dobryszycka and Owczarek (1981) following subacute intoxication of rats with Pb-, Cu-, and Zn-salts (separately or in mixture) for 5 weeks, (LDH) estimated in serum and in cytoplasmic fraction of the kidney. LDH activity was no affect; however, mixture of these metals caused a significant rise in the enzymatic activity.…”