Sodium Oleate: A Dual-Action Compound Enhancing Antibiotic Efficacy While Inducing Hepatotoxicity

General Description

Sodium oleate has shown promising potential in enhancing the sensitivity of Methylophilus quaylei biofilms to ampicillin by disrupting biofilm integrity and improving antibiotic penetration. This combination effectively inhibits biofilm formation and destabilizes established biofilms, offering a novel therapeutic strategy against biofilm-associated infections. However, sodium oleate also induces steatosis and inflammation in hepatocytes, leading to decreased cell viability, increased lipid accumulation, and heightened inflammatory responses mediated by Toll-like receptor 2 and nuclear factor-κB pathways. Understanding these dual effects is crucial for optimizing sodium oleate's application in combating antibiotic resistance while mitigating its hepatotoxicity.

Figure 1. Sodium oleate

Enhancing Ampicillin Sensitivity in Methylophilus quaylei Biofilms

Sodium oleate, a sodium salt of oleic acid, has emerged as a promising agent in combating bacterial biofilm resistance. In recent studies, sodium oleate has shown significant potential when combined with antibiotics like ampicillin. This synergy addresses the challenge of biofilm-associated infections, particularly those caused by Methylophilus quaylei.

Mechanism of Action

The effectiveness of sodium oleate lies in its ability to disrupt biofilm integrity and enhance antibiotic penetration. Biofilms of M. quaylei, known for their resistance to conventional treatments, exhibit increased susceptibility when exposed to a combination of ampicillin and sodium oleate. This combination not only inhibits biofilm formation but also destabilizes established biofilms, as demonstrated by reduced colony forming units (CFUs) and notable destruction under microscopy. ¹

Practical Implications and Future Applications

The practical implications of these findings suggest a potential therapeutic strategy against biofilm-associated infections. By augmenting the bactericidal activity of ampicillin, sodium oleate offers a novel approach to treating M. quaylei biofilms on surfaces like Teflon and polypropylene. Further research could explore optimized dosages and application methods to maximize efficacy while minimizing cytotoxicity, paving the way for clinical trials and eventual therapeutic use. In summary, sodium oleate represents a significant advancement in biofilm management, particularly in enhancing the effectiveness of antibiotics against M. quaylei biofilms. This approach not only addresses current challenges in antibiotic resistance but also opens avenues for innovative treatments in biomedical and environmental settings.

The study's results underscore the potential of sodium oleate as a synergistic agent in combination therapies, highlighting its role in combating biofilm-related antibiotic resistance. This research provides a foundation for future investigations into enhancing the efficacy of existing antibiotics through combination therapies involving sodium oleate. ¹

Side Effects

Impact of Sodium Oleate on Hepatocyte Function

Sodium oleate, a fatty acid salt, has been identified to induce steatosis and inflammation in L02 hepatocytes, according to recent studies. Research highlights that upon exposure to various concentrations of sodium oleate, L02 cells demonstrate a marked decrease in viability and an increase in growth inhibition. Specifically, the lipid accumulation within the cells significantly escalates with higher doses of sodium oleate, as evidenced by oil red staining. This accumulation correlates with the elevated levels of triglycerides, which starkly contrasts with control groups, indicating a disruptive metabolic response induced by sodium oleate. Furthermore, the inflammatory response is augmented as the concentration of interleukin-6 (IL-6) in the cell supernatant increases with the sodium oleate dosage, underscoring the compound’s role in inflammatory processes within hepatocytes. ²

Molecular Mechanisms Behind Sodium Oleate Induced Pathology

The molecular pathways affected by sodium oleate provide insights into its detrimental effects on hepatocyte health. The expression of Toll-like receptor 2 (TLR2) is significantly enhanced in cells treated with medium to high concentrations of sodium oleate, unlike Toll-like receptor 4 (TLR4), which does not show similar changes. This suggests that TLR2 may play a crucial role in mediating the inflammatory response to sodium oleate. Additionally, the sodium oleate-treated cells exhibit a decrease in SIRT1 protein levels, accompanied by an increase in the activation of nuclear factor-κB (NF-κB) p65. These alterations indicate that sodium oleate not only prompts lipid accumulation but also triggers an inflammatory pathway mediated by TLR2 and NF-κB, leading to cellular stress and potentially contributing to the pathogenesis of liver diseases. Thus, understanding these molecular interactions is essential for comprehending the full spectrum of sodium oleate's impact on liver health. ²

Reference

1. Mohamed AMHA, Vladimirovna SN, Grigorievich ZV, Borisovna PA, Ivanovich SV. Sodium Oleate Increases Ampicillin Sensitivity in Methylophilus quaylei Biofilms on Teflon and Polypropylene. Curr Pharm Biotechnol. 2019; 20(3): 261-270.

2. Chen C, Ma Y, Gong W, et al. Steatosis and inflammation of L02 hepatocytes induced by sodium oleate. Wei Sheng Yan Jiu. 2020; 49(3): 381-385.

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