Antimicrobial, Immunomodulatory and Anti-Inflammatory Potential of Liposomal Thymoquinone: Implications in the Treatment of Bacterial Pneumonia in Immunocompromised Mice.

Khaled S Allemailem,Masood Alam Khan,Ahmad Almatroudi,Amjad Ali Khan,Aseel Aljaghwani,Faris Alrumaihi,Fahad M Aldakheel,Asmaa M El-Kady,Abdullah M Alnuqaydan,Habibullah Khalilullah,Arif Khan,Hina Younus

doi:10.3390/biomedicines9111673

Khaled S Allemailem, Masood Alam Khan + Show 10 more

Open Access

https://doi.org/10.3390/biomedicines9111673

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Abstract

Acinetobacter baumannii has recently been increasing as an aggressive pathogen in immunocompromised persons. In the present study, we determined the in vitro antibacterial and anti-biofilm activity of thymoquinone (TQ) against A. baumannii. A liposomal formulation of TQ (Lip-TQ) was prepared and its therapeutic potential was investigated in the treatment of A. baumannii infection in immunocompromised mice. Leukopenia was induced in mice by injecting cyclophosphamide (CYP) at a dose of 200 mg/kg and the leukopenic mice were infected with 1 × 106 CFUs of A. baumannii. The effectiveness of free TQ or Lip-TQ against A. baumannii infection was assessed by analyzing the survival rate and bacterial burden. Moreover, the efficacy of Lip-TQ was also studied by examining the systemic inflammatory markers and the histological changes in the lung tissues. The results showed that the mice in the group treated with Lip-TQ at a dose of 10 mg/kg exhibited a 60% survival rate on day 40 post-infection, whereas all the mice treated with free TQ at the same dose died within this duration. Likewise, the lowest bacterial burden was found in the lung tissue of mice treated with Lip-TQ (10 mg/kg). Besides, Lip-TQ treatment remarkably alleviated the infection-associated inflammation, oxidative stress, and histological changes in the lung tissues. Based on the findings of the present study, we recommend considering Lip-TQ as a valuable therapeutic formulation in the treatment of A. baumannii-associated pneumonia in immunocompromised subjects.

Highlights

Introduction conditions of the Creative CommonsIn recent years, Acinetobacter baumannii infections have posed a massive challenge for clinicians due to its increasing prevalence in vulnerable persons [1,2]
A. baumannii infection results in the recruitment of neutrophils to the infection site in order to combat the bacteria by releasing multiple molecules, including myeloperoxidase, reactive oxygen species (ROS), β-defensins, cytokines, and chemokines [3]
Garcia-Patino et al extensively reviewed the important role of neutrophils and other immune cells against A. baumannii infection [20]

Summary

Introduction

Acinetobacter baumannii infections have posed a massive challenge for clinicians due to its increasing prevalence in vulnerable persons [1,2]. The cells of the innate immune system, neutrophils and macrophages, play a very important. Biomedicines 2021, 9, 1673 role in combating A. baumannii [3]. Immunocompromised mice demonstrated more severe pneumonia and an early impairment of the lung function [4]. Neutropenia has been reported to increase the susceptibility of mice to A. baumannii [5]. A. baumannii has shown a remarkable degree of resistance to commonly used first-line antibiotics [6]

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