Protection against cadmium toxicity and enzyme inhibition by dithiothreitol

Abstract

In the present in vivo studies the alterations in cation transporting enzymes of the brain, kidney and liver tissues were assessed at intervals between 0 to 48 h after a single, acute (10 mg kg⁻¹, i.p.) dose of cadmium (Cd). The inhibition of Na⁺–K⁺–ATPase during the first 24 h does not parallel the changes in K⁺–PNPPase suggesting differential effects on phosphorylation and dephosphorylation steps of the overall ATPase reaction. Between 30 min to 2 h the inhibition in enzyme activity was steep (27 per cent in brain, 54 per cent in liver) followed by a rapid reversal between 2–6 h. This critical period may correspond to the time of induction of metallothionin. This enzyme reversal was followed by a significant decrease in Na⁺–K⁺ ATPase (40–68 per cent) and K⁺‐PNPPase (44–60 per cent) between 24 to 48 h. A similar pattern was observed in Ca²⁺–ATPase in all the three tissues. A 33 per cent mortality was observed in rats after 48 h of cadmium challenge. Administration of dithiothreitol (DTT, 20 mg kg⁻¹, i.p.) to CdCl₂ pretreated rats at 24 h resulted in mortality reduced from 33 per cent to 0 and reversal in the inhibition of Na⁺‐‐K⁺–ATPase in brain and kidney and Ca²⁺–ATPase in brain. Since protection of brain and kidney enzymes by DTT paralleled its protection against Cd toxicity, their inhibition by Cd may, in part, constitute the biochemical basis of Cd toxicity.