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[Effect of mellaril on the liver lysosomes of rats with acute toxic hepatitis]
Abstract:
In 24 hours after a single administration of melleril (30 mg/kg) an elevated injuriousness of "heavy" and "light" liver lysosomes of rats subjected to "in vitro" treatment with a pH 5.0 solution at 37 degrees was recorded. Introduction of melleril to rats with toxic CCl4-induced hepatitis (CCl4 dosage of 0.15 ml per 100 g body weight) depresses free activity of acid phosphatase, this fall, however, failing to reach the corresponding values in intact animals. An elevated injuriousness of "heavy" and "light" lysosomas undergoing treatment at pH 5.0 and 37degrees, revealed in all variants of the tests, is related to activation of lysosomal phospholipases with subsequent liberation of surfactant lipids and volumetric changes of the particles.
Insights
Melleril administration increased liver lysosome fragility in rats, affecting acid phosphatase activity in CCl4-induced hepatitis. This damage is linked to lysosomal phospholipase activation and particle volume changes.
Area of Science:
- Hepatology
- Toxicology
- Cell Biology
Background:
- Carbon tetrachloride (CCl4) is a known hepatotoxin.
- Lysosomes are key organelles involved in cellular degradation and homeostasis.
- Drug-induced liver injury is a significant clinical concern.
Purpose of the Study:
- To investigate the effects of Melleril on rat liver lysosomes.
- To assess Melleril's impact on acid phosphatase activity in toxic hepatitis.
- To elucidate the mechanisms underlying Melleril-induced lysosomal injury.
Main Methods:
- Administration of Melleril (30 mg/kg) to rats.
- Induction of toxic hepatitis using carbon tetrachloride (CCl4).
- In vitro assessment of lysosomal fragility at pH 5.0 and 37°C.
- Measurement of acid phosphatase activity in liver homogenates.
Main Results:
- Melleril increased the fragility of "heavy" and "light" liver lysosomes 24 hours post-administration.
- In CCl4-induced hepatitis, Melleril depressed free acid phosphatase activity, though not to levels seen in intact animals.
- Elevated lysosomal fragility was observed across all tested conditions, linked to phospholipase activation and lipid release.
Conclusions:
- Melleril exhibits injurious effects on rat liver lysosomes, particularly under acidic conditions.
- The drug modulates acid phosphatase activity in the context of toxic hepatitis.
- Lysosomal phospholipase activation and subsequent surfactant lipid liberation contribute to Melleril-induced lysosomal damage.