Effect of hexachlorobenzene on haem synthesis

Area of Science:

• Biochemistry
• Toxicology
• Pharmacology

Background:

• Drug administration can induce the liver microsomal mixed-function oxidase system.
• This induction is often linked to increased delta-aminolaevulinate synthetase, heme synthesis, and cytochrome P-450.
• The precise sequence and regulation of these events are not fully understood.

Purpose of the Study:

• To investigate the effects of the fungicide hexachlorobenzene on liver enzyme systems in female rats.
• To determine the relationship between hexachlorobenzene exposure, cytochrome P-450 levels, heme synthesis, and delta-aminolaevulinate synthetase activity.

Main Methods:

• Administration of hexachlorobenzene to female rats.
• Measurement of cytochrome P-450 content and synthesis rates.
• Assay of total heme synthesis rates.
• Determination of delta-aminolaevulinate synthetase activity.

Main Results:

• Hexachlorobenzene enhanced cytochrome P-450 amounts and synthesis rates without initially altering total heme synthesis.
• Initial increases in cytochrome P-450 occurred when delta-aminolaevulinate synthetase activity remained constant.
• Prolonged hexachlorobenzene administration led to a twofold increase in delta-aminolaevulinate synthetase activity, associated with porphyria.

Conclusions:

• Hexachlorobenzene can induce cytochrome P-450 independently of initial changes in total heme synthesis.
• The increase in delta-aminolaevulinate synthetase activity during prolonged exposure appears to be due to reduced enzyme degradation.
• These findings provide new insights into the mechanisms of drug-induced liver enzyme regulation and potential toxicity.