Effect of temperature on the inhibition of rat brain synaptosomal ATPases by DDT and its structural analogs
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Abstract:
In vitro effects of DDT and its isomers or metabolites were studied on Na+-K+-ATPase and oligomycin-sensitive (OS) Mg++-ATPase activities at 17, 27 and 37 degrees C in rat brain synaptosomes. Dicofol and methoxychlor were found to be more effective inhibitors of Na+-K+-ATPase and OS Mg++-ATPase than DDT, DDD and DDE. Inhibition of OS Mg++-ATPase by the compounds tested (except DDE) was found to be greater at 17 degrees C than at higher temperatures (17 greater than 27 greater than 37 degrees C), suggesting a negative temperature correlation trend Na+-K+-ATPase was less sensitive to these compounds when compared with OS Mg++-ATPase and the inhibition was greater at higher temperatures (37 greater than 27 greater than 17 degrees C), suggesting a positive temperature correlation trend. Other DDT isomers and metabolites showed variable effects on Na+-K+-ATPase and OS Mg++-ATPases. DDD, but not DDE, inhibited both enzyme activities and the inhibition was independent of temperature. No significant differences were observed in the inhibitory potencies of the various DDT, DDD or DDE ring substitutes studied. The present data indicate that DDT, dicofol and methoxychlor were more effective inhibitors of OS Mg++-ATPase than Na+-K+-ATPase and that the inhibition of the former enzyme had a negative temperature dependence, a feature which parallels toxicity results in insects.
Insights
DDT and its related compounds inhibit key enzymes in rat brain synaptosomes. Dicofol and methoxychlor were potent inhibitors, with effects varying by enzyme and temperature.
Area of Science:
- Biochemistry
- Neurotoxicology
- Environmental Science
Background:
- Organochlorine pesticides like DDT can impact neurological functions.
- ATPases are crucial enzymes involved in cellular energy and ion transport.
- Understanding the in vitro effects of DDT metabolites on enzyme activity is important for assessing neurotoxicity.
Purpose of the Study:
- To investigate the in vitro effects of DDT and its isomers/metabolites on Na+-K+-ATPase and oligomycin-sensitive (OS) Mg++-ATPase activities.
- To determine the influence of temperature on the inhibitory effects of these compounds.
- To compare the inhibitory potency of DDT, dicofol, methoxychlor, DDD, and DDE on specific ATPase activities.
Main Methods:
- Enzyme activity assays were performed on rat brain synaptosomes.
- The effects of DDT, dicofol, methoxychlor, DDD, and DDE were tested at 17, 27, and 37 degrees C.
- Inhibition percentages for Na+-K+-ATPase and OS Mg++-ATPase were quantified.
Main Results:
- Dicofol and methoxychlor were more effective inhibitors of both Na+-K+-ATPase and OS Mg++-ATPase than DDT, DDD, and DDE.
- Inhibition of OS Mg++-ATPase by most compounds showed a negative temperature correlation (greater inhibition at lower temperatures).
- Na+-K+-ATPase inhibition exhibited a positive temperature correlation (greater inhibition at higher temperatures), and was less sensitive than OS Mg++-ATPase.
Conclusions:
- DDT, dicofol, and methoxychlor are more potent inhibitors of OS Mg++-ATPase than Na+-K+-ATPase.
- The negative temperature dependence of OS Mg++-ATPase inhibition by these compounds aligns with observed insect toxicity.
- The differential effects on ATPase activities and temperature dependence provide insights into the neurotoxic mechanisms of DDT and its analogs.