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Published on: April 2, 2017
[Effects of selective induceble nitric oxide synthase inhibitor on immunological hepatic injury in rat]
Objective:
To investigate the role and induced regulation of nitric oxide (NO) in rat immunological hepatic injury, and the effect of selective inhibitor on induceble nitric oxide synthase (iNOS).
Methods:
The intracellular NOS gene expression in the immune damaged hepatocytes was determined by in situ PCR technique, and NO concentration and lactate dehydrogenase (LDH) activity in culture supernatant were measured.
Results:
Administration of bacille calmette guerin (BCG, 15, 30, 50 mg/rat, i.v.) alone or BCG with the inflammatory cytokines mixture (CM), including IL-1 beta, IFN-gamma, TNF-alpha and lipopolysacchride (LPS) significantly increased NO production and LDH release in culture medium(P < 0.05). NO production was enhanced with hepatic injury degree in direct proportion, and with BCG dose in inverse proportion. Under immunological stimuli condition, hepatocytes NOS mRNA mainly expressed an induceble and soluble isoform (iNOS) in cytoplasm. Aminoguanidine (AG), a selective iNOS inhibitor, inhibited NO production and LDH release (83.4% and 36.0%, P < 0.05), but the transcription inhibitor actinomycin D enhanced LDH level in the medium (25.5%, P < 0.05).
Conclusion:
NO produced by immunological stimuli participates in rat hepatic injury mechanism.
Insights
Nitric oxide (NO) produced during immunological stimuli contributes to rat liver injury. An inducible nitric oxide synthase (iNOS) inhibitor reduced NO production and liver damage markers.
Area of Science:
- Immunology
- Hepatology
- Biochemistry
Background:
- Immunological hepatic injury is a complex process.
- The role of nitric oxide (NO) in this injury is not fully understood.
- Investigating the regulation of inducible nitric oxide synthase (iNOS) is crucial.
Purpose of the Study:
- To explore the function and regulation of NO in rat immunological hepatic injury.
- To assess the impact of a selective iNOS inhibitor on this process.
Main Methods:
- In situ PCR was used to determine intracellular NOS gene expression in immune-damaged hepatocytes.
- NO concentration and lactate dehydrogenase (LDH) activity were measured in culture supernatants.
- The effects of bacille calmette guerin (BCG) and inflammatory cytokines were evaluated.
Main Results:
- BCG administration, alone or with inflammatory cytokines, significantly increased NO production and LDH release (P < 0.05).
- Hepatocytes primarily expressed iNOS mRNA under immunological stimuli.
- Aminoguanidine (AG), an iNOS inhibitor, reduced NO production and LDH release, while actinomycin D enhanced LDH levels.
Conclusions:
- NO generated by immunological stimuli plays a role in the mechanism of rat hepatic injury.
- Targeting iNOS may offer a therapeutic strategy for immunological liver damage.
