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Effects of dichlorodiphenyltrichloroethane and its analogues on rat liver mitochondria
Abstract:
The effects of dichlorodiphenyltrichloroethane (DDT) and sixteen analogues on respiration, swelling and latent ATPase of rat liver mitochondria were examined systematically. The compounds tested could be divided into four groups: DDT-type, DDE-type, kelthane-type and others by substituent groups on the ethane bridge of bis(p-chlorophenyl) ethane. Most compounds tested were shown to inhibit State 3 respiration. A linear relation was observed between the logarithms of the concentrations giving half-inhibition of State 3 respiration and the logarithms of the partition coefficients of the tested compounds. Four compounds of the kelthane type and chlorobenzilate stimulated State 4 respiration to the level of dinitrophenol-stimulated respiration. The compounds that have a hydroxy group on the ethane bridge-rapidly induced mitochondrial swelling, but DDT-type and DDE-type compounds induced swelling when the suspension contained 0.15 M KCl and 5 mM Tris-HCl. Latent ATPase of mitochondria was stimulated to different maximum levels by each of the tested compounds except DDA. The oligomycin-sensitive ATPase of submitochondria was inhibited by a series of kelthane-type compounds.
Insights
Dichlorodiphenyltrichloroethane (DDT) and its analogues impact rat liver mitochondria function, affecting respiration and ATPase activity. These compounds disrupt mitochondrial energy production and membrane integrity, with varying effects based on chemical structure.
Area of Science:
- Biochemistry
- Toxicology
- Mitochondrial Physiology
Background:
- Mitochondria are crucial for cellular energy production.
- Dichlorodiphenyltrichloroethane (DDT) and its analogues are environmental contaminants with known toxic effects.
- The specific mechanisms by which DDT and its analogues affect mitochondrial function require further elucidation.
Purpose of the Study:
- To systematically investigate the effects of DDT and sixteen analogues on rat liver mitochondria.
- To analyze the impact of these compounds on mitochondrial respiration, swelling, and latent ATPase activity.
- To correlate the chemical structure of DDT analogues with their observed effects on mitochondrial function.
Main Methods:
- Isolated rat liver mitochondria were used for experimental analysis.
- Mitochondrial respiration (State 3 and State 4) was measured.
- Mitochondrial swelling was induced and monitored.
- Latent and oligomycin-sensitive ATPase activities were assayed.
- Compounds were categorized into DDT-type, DDE-type, kelthane-type, and others based on structural features.
Main Results:
- Most DDT analogues inhibited State 3 mitochondrial respiration.
- A linear correlation was found between inhibitory concentrations and partition coefficients.
- Kelthane-type compounds and chlorobenzilate stimulated State 4 respiration.
- Hydroxy-containing analogues rapidly induced mitochondrial swelling.
- Latent ATPase was stimulated by most analogues, except DDA.
- Kelthane-type compounds inhibited oligomycin-sensitive ATPase.
Conclusions:
- DDT and its analogues exhibit diverse effects on mitochondrial bioenergetics.
- The chemical structure significantly influences the mode and potency of mitochondrial disruption.
- These findings provide insights into the molecular mechanisms of DDT toxicity at the mitochondrial level.