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Melatonin counteracts lipopolysaccharide-induced expression and activity of mitochondrial nitric oxide synthase in
Germaine Escames1, Josefa León, Manuel Macías
1Departamento de Fisiología, Instituto de Biotecnología, Universidad de Granada, Granada, Spain.
Abstract:
Mitochondrial nitric oxide synthase (mtNOS) is expressed constitutively, although it might be induced. Nitric oxide (NO) is a physiological regulator of mitochondrial respiration. Melatonin prevents mitochondrial oxidative damage and inhibits iNOS expression induced by bacterial lipopolysaccharide (LPS). The loss of melatonin with age may be related to the age-dependent mitochondrial damage. Thus, we examined the protective role of melatonin against the effects of LPS on mtNOS and on respiratory complexes activity in liver and lung mitochondria from young and old rats. The activity of mtNOS in control lung was low and did not change with age. LPS administration (10 mg/kg, i.v.) significantly increased mtNOS expression and activity and NO production in lung mitochondria, and the effect was greater in old rats. LPS administration also reduced the age-dependent decrease of the respiratory complexes I and IV. Melatonin administration (60 mg/kg, i.p.) prevented the LPS toxicity, decreasing mitochondrial NOS activity and NO production. Melatonin also counteracted LPS-induced inhibition of complexes I and IV. In general, the actions of melatonin were stronger in older animals than in younger ones. The results suggest that an inducible component of mtNOS, together with mitochondrial damage, occurs during sepsis, and melatonin prevents the mitochondrial failure that occurs during endotoxemia.
Insights
Melatonin protects against mitochondrial damage caused by bacterial lipopolysaccharide (LPS) in rats. This protective effect, particularly in older animals, highlights melatonin
Area of Science:
- Mitochondrial physiology
- Endocrinology
- Toxicology
Background:
- Mitochondrial nitric oxide synthase (mtNOS) regulates mitochondrial respiration.
- Melatonin (a hormone) protects against oxidative damage and inhibits inducible nitric oxide synthase (iNOS).
- Age-related decline in melatonin may contribute to mitochondrial dysfunction.
Purpose of the Study:
- To investigate melatonin's protective effects against lipopolysaccharide (LPS)-induced mitochondrial dysfunction.
- To examine the impact of LPS on mtNOS and respiratory complex activity in young and old rats.
- To assess melatonin's role in mitigating LPS toxicity in mitochondria.
Main Methods:
- Mitochondrial isolation from rat liver and lungs (young and old).
- Administration of LPS and melatonin via intravenous and intraperitoneal routes, respectively.
- Measurement of mtNOS activity, nitric oxide (NO) production, and respiratory complex I and IV activity.
Main Results:
- LPS increased mtNOS activity and NO production in lung mitochondria, more significantly in older rats.
- LPS administration attenuated the age-dependent decline in respiratory complexes I and IV activity.
- Melatonin administration counteracted LPS-induced mtNOS activation, NO production, and inhibition of respiratory complexes I and IV.
- Melatonin's protective effects were more pronounced in older rats.
Conclusions:
- An inducible component of mtNOS and mitochondrial damage occur during sepsis.
- Melatonin effectively prevents mitochondrial failure during endotoxemia.
- Melatonin's protective role against LPS-induced mitochondrial dysfunction is significant, especially in aging animals.
