Chlorogenic acid prevents vancomycin-induced nephrotoxicity without compromising vancomycin antibacterial properties.

Vancomycin (VCM) is an effective chemotherapeutic agent commonly used against gram-positive microorganisms but has serious nephrotoxic side effects that limit its effectiveness. New therapeutics and strategies are urgently needed to combat VCM associated nephrotoxicity. In this study, we determined the protective effect of chlorogenic acid (CA) in a rat model of VCM-induced nephrotoxicity. VCM administration led to markedly elevated blood urea nitrogen and serum creatinine levels that could be prevented with CA co-administration. VCM-mediated oxidative stress was also significantly attenuated by CA as reflected by decreased malondialdehyde and nitric oxide in VCM-treated kidneys. CA administration also prevented the VCM-mediated decrease in the renal antioxidative enzyme activities of glutathione reductase, glutathione peroxidase, and catalase and led to increased levels of reduced glutathione that had been depleted by VCM. Moreover, CA administration clearly inhibited VCM-induced expression of nuclear factor-kappa B, inducible nitric oxide synthase and the downstream pro-inflammatory mediators tumor necrosis factor-α and interleukins 1ß and 6. Apoptotic markers were also markedly down-regulated with CA. Overall, CA treatment mitigated VCM-induced oxidative and nitrosative stresses and countered the apoptotic and inflammatory effects of VCM. Notably, CA did not affect the antibacterial activity of VCM in vitro.

Programmable antibiotic delivery to combat methicillin-resistant Staphylococcus aureus through precision therapy.

The rapid dissemination of life-threatening multidrug-resistant bacterial pathogens calls for the development of new antibacterial agents and alternative strategies. The virulence factor secreted by bacteria plays a crucial role in the sophisticated processes during infections. Inspired by the unique capacity of many bacteria inducing clotting of plasma to initiate colonization, we propose a programmable antibiotic delivery system for precision therapy using methicillin-resistant S. aureus (MRSA) as a model. Coagulase utilized by MRSA to directly cleave fibrinogen into fibrin, is an ideal target not only for tracking bacterial status but for triggering the collapse of fibrinogen functionalized porous microspheres. Subsequently, staphylokinase, another virulence factor of MRSA, catalyzed hydrolysis of fibrin to further release the encapsulated antibiotics from microspheres. Our sequential triggered-release system exhibits high selectivity to distinguish live or dead MRSA from other pathogenic bacteria. Furthermore, such programmable microspheres clear 99% MRSA in 4 h, and show increased efficiency in a wound healing model in rats. Our study provides a programmable drug delivery system to precisely target bacterial pathogens using their intrinsic enzymatic cascades. This programmable platform with reduced selective stress of antibiotics on microbiota sheds light on the potential therapy for future clinical applications.

Rutin attenuates vancomycin-induced renal tubular cell apoptosis via suppression of apoptosis, mitochondrial dysfunction, and oxidative stress.

Vancomycin is a glycopeptide antibiotic widely used to treat infections caused by methicillin-resistant Staphylococcus aureus. However, nephrotoxicity is a major adverse side effect, and the development of effective nephroprotective agents remains a priority in antimicrobial chemotherapy. In this study, we investigated the cell protective effects of the flavonol glycoside rutin against vancomycin-induced toxicity. Vancomycin added to porcine renal tubular LLC-PK1 cells caused an increase of production of intracellular reactive oxygen species and subsequent apoptotic cell death. Pretreatment of LLC-PK1 cells with rutin at 5, 10, and 20 µM for 2 hr prior to 2-mM vancomycin exposure for 24 hr significantly decreased intracellular reactive oxygen species and increased superoxide dismutase and catalase activities. Rutin pretreatment also protected cells from vancomycin-induced caspase activation, mitochondrial membrane depolarization, and subsequent apoptosis. This study demonstrates a protective effect of rutin and suggests that rutin coadministration is an alternative therapy for treatment of vancomycin-induced nephrotoxicity.

Effects of pidotimod soluble powder and immune enhancement of Newcastle disease vaccine in chickens.

The aims of this study were to prepare pidotimod (PDM) soluble powder and to investigate the immune enhancement properties of PDM in chickens vaccinated with Newcastle disease virus vaccine. In vivo experiment, 360 6-day-old chickens were averagely divided into 6 groups. The chickens, except blank control (BC) group, were vaccinated with Newcastle disease vaccine (NDV). At the same time of the vaccination, the chickens in three PDM groups were given water with PDM for 5days, respectively, with the PDM at low, medium and high concentrations (0.25g/L, 0.5g/L, 1g/L), in control drug group was treated with 0.2ml/PDM dose via drinking water, in vaccination control (VC) and BC group, with equal volume physiological saline, once a day for five successive days. On days 14, 21 and 28 after the vaccination, the growth performance, the lymphocyte proliferation, serum antibody titer, the CD4/CD8 cell ratios and interleukin-2 (IL-2) and interferon-gamma (IFN-γ) were measured. The results showed that PDM at suitable dose could significantly promote growth performance, lymphocyte proliferation, enhance serum antibody titer, CD4/CD8 cell ratios and improve serum IL-2 and IFN-γ concentrations. It indicated that PDM could significantly improve the immune efficacy of Newcastle disease vaccine using doses of 0.5g/L, these results are consistent with the drug acting as an immunopotentiator.