ArticleNaunyn-Schmiedeberg's archives of pharmacology2025
Protective effect of valsartan alone and in combination with neprilysin inhibitor (valsartan + sacubitril) against hepatic ischemia-reperfusion injury: targeting angiotensin II receptor-neprilysin and modulating SMAD-4/NF-κβ/JNK pathways in rats.
Article in Naunyn-Schmiedeberg's archives of pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed.
- Dynamic regulation and targeted intervention of neutrophils in hepatic ischemia‑reperfusion injury (Review).International journal of molecular medicine · 2026Review
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ischemia-reperfusion injury (IRI) is a common pathogenic situation that arises throughout all liver surgeries, including liver transplants. We aimed to compare the preventive effects of valsartan (VST) against valsartan + sacubitril (LCZ696) on hepatic injury caused by IRI. A total of thirty-six male Westar albino rats were split into six groups randomly: sham, IRI, VST + IRI, LCZ696 + IRI, VST, and LCZ696. The medicines were given orally for 10 days in a row. Hepatic tissues and blood were examined through histopathological imaging and immunohistochemical detection of hepatic SMAD-4 protein expression plus serum aminotransferase (ALT, AST) and gamma-glutamyl transferase (GGT) levels. Angiotensin II, aldosterone, and plasma renin activity were evaluated in rat serum. Liver tissue homogenate was utilized to assess reduced glutathione (GSH), myeloperoxidase (MPO), malondialdehyde (MDA), and total nitric oxide (NOx) levels. Pro-inflammatory indicators, tumor necrosis factor-alpha (TNF-α), and interleukin-1β (IL-1β), moreover with apoptosis indicators, BCL2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), and galactine-9 (GAL9) proteins plus caspase-3, were measured in hepatic tissue homogenate. Hepatic endothelin-1 and neprilysin activity were evaluated. Western blot was done for c-Jun N-terminal kinase (JNK-7) plus nuclear factor-kappa B (NF-κβ) expressions. The study revealed that VST and LCZ696 pretreatment showed significant restoration of liver injury, correction of oxidative profile, and inhibition in the angiotensin II receptor-neprilysin pathway. Inflammatory mediators and apoptosis were significantly inhibited. The expression of SMAD-4, JNK-7, and NF-κβ proteins was notably diminished. The improvement in hepatic architecture supports these histopathological results. In conclusion, LCZ696 possesses a potentially significant protective effect against liver IRI superior to VST alone.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.