L-ornithine liposomal nanoparticles as a potent candidate for hepatic encephalopathy therapy via inhibiting Δ1-pyrroline-5-carboxylate dehydrogenase.

Hepatic encephalopathy (HE), a neuropsychiatric condition linked to liver malfunction and hyperammonemia. This study aims to investigate the therapeutic efficacy of L-ornithine liposomal nanoparticles in a rat model of HE, focusing on their capacity to inhibit Δ1-pyrroline-5-carboxylate dehydrogenase (∆1P5CDH) in HE rat model. Ten experimental groups were formed: G1-G4 acted as negative controls, G5 served as the untreated HE- control, and G6-G10 received treatments with L-ornithine, L-ornithine liposomal nanoparticles, or LOLA, either individually or in combination. A variety of assessments were performed, encompassing body weight monitoring, behavioral analysis, oxidative stress markers, inflammatory gene expression, (IL-1β, NF-κβ, IL-6, IL-10, TNFα, iNOS, TGF-β), protein expression for target ∆1P5CDH and histological evaluation. The untreated HE group displayed notable abnormalities, such as augmented liver and brain weights, cognitive deficits, hyperammonemia, oxidative stress, and neuroinflammation. Treatment with L-ornithine, LOLA, and particularly L-ornithine liposomal nanoparticles resulted in significant enhancements by diminishing ammonia toxicity, re-establishing neurotransmitter equilibrium, decreasing oxidative stress, downregulating pro-inflammatory cytokine expression, and suppressing target protein ∆1P5CDH, a key enzyme in proline metabolism. Histological features showed a reduction in hepatocellular degeneration and stored the nervous tissue function in the treatment groups compared with the HE untreated group. Thus, our findings elucidated that L-ornithine liposomal nanoparticles could serve as a potent therapeutic agent for HE therapy.