ABSTRACT
Individuals with uncontrolled diabetes are highly susceptible to tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tb) infection. Novel treatments for TB are needed to address the increased antibiotic resistance and hepatoxicity. Previous studies showed that the administration of liposomal glutathione (L-GSH) can mitigate oxidative stress, bolster a granulomatous response, and diminish the M. tb burden in the lungs of M. tb-infected mice. Nonetheless, the impact of combining L-GSH with conventional TB treatment (RIF) on the cytokine levels and granuloma formation in the livers of diabetic mice remains unexplored. In this study, we evaluated hepatic cytokine profiles, GSH, and tissue pathologies in untreated and L-GSH, RIF, and L-GSH+RIF treated diabetic (db/db) M. tb-infected mice. Our results indicate that treatment of M. tb-infected db/db mice with L-GSH+RIF caused modulation in the levels of pro-inflammatory cytokines and GSH in the liver and mitigation in the granuloma size in hepatic tissue. Supplementation with L-GSH+RIF led to a decrease in the M. tb burden by mitigating oxidative stress, promoting the production of pro-inflammatory cytokines, and restoring the cytokine balance. These findings highlight the potential of L-GSH+RIF combination therapy for addressing active EPTB, offering valuable insights into innovative treatments for M. tb infections.
ABSTRACT
Mycobacterium avium (M. avium), a type of nontuberculous mycobacteria (NTM), poses a risk for pulmonary infections and disseminated infections in immunocompromised individuals. Conventional treatment consists of a 12-month regimen of the first-line antibiotics rifampicin and azithromycin. However, the treatment duration and low antibiotic tolerability present challenges in the treatment of M. avium infection. Furthermore, the emergence of multidrug-resistant mycobacterium strains prompts a need for novel treatments against M. avium infection. This study aims to test the efficacy of a novel antimicrobial peptide, cyclic [R4W4], alongside the first-line antibiotics azithromycin and rifampicin in reducing M. avium survival. Colony-forming unit (CFU) counts were assessed after treating M. avium cultures with varying concentrations of cyclic [R4W4] alone or in conjunction with azithromycin or rifampicin 3 h and 4 days post-treatment. M. avium growth was significantly reduced 4 days after cyclic [R4W4] single treatment. Additionally, cyclic [R4W4]-azithromycin and cyclic [R4W4]-rifampicin combination treatments at specific concentrations significantly reduced M. avium survival 3 h and 4 days post-treatment compared with single antibiotic treatment alone. These findings demonstrate cyclic [R4W4] as a potent treatment method against M. avium and provide insight into novel therapeutic approaches against mycobacterium infections.
ABSTRACT
Glutathione (GSH) is an important intracellular antioxidant responsible for neutralizing reactive oxygen species (ROS). Our laboratory previously demonstrated that the oral administration of liposomal GSH improves immune function against mycobacterium infections in healthy patients along with patients with HIV and Type 2 diabetes. We aim to determine if the topical application of a glutathione-cyclodextrin nanoparticle complex (GSH-CD) confers a therapeutic effect against mycobacterium infections. In our study, healthy participants received either topical GSH-CD (n = 15) or placebo (n = 15) treatment. Subjects were sprayed four times twice a day for three days topically on the abdomen. Blood draws were collected prior to application, and at 1, 4, and 72 h post-initial topical application. GSH, malondialdehyde (MDA), and cytokine levels were assessed in the processed blood samples of study participants. Additionally, whole blood cultures from study participants were challenged with Mycobacterium avium (M. avium) infection in vitro to assess mycobacterium survival post-treatment. Topical GSH-CD treatment was observed to elevate GSH levels in peripheral blood mononuclear cells (PBMCs) and red blood cells and decrease MDA levels in PBMCs 72 h post-treatment. An increase in plasma IL-2, IFN-γ, IL-12p70, and TNF-α was observed at 72 h post-topical GSH-CD treatment. Enhanced mycobacterium clearance was observed at 4 h and 72 h post-topical GSH-CD treatment. Overall, topical GSH-CD treatment was associated with improved immune function against M. avium infection. The findings of this pilot study suggest GSH-cyclodextrin complex formulation can be used topically as a safe alternative mode of GSH delivery in the peripheral blood.
ABSTRACT
Coronaviruses represent a diverse family of enveloped positive-sense single stranded RNA viruses. COVID-19, caused by Severe Acute Respiratory Syndrome Coronavirus-2, is a highly contagious respiratory disease transmissible mainly via close contact and respiratory droplets which can result in severe, life-threatening respiratory pathologies. It is understood that glutathione, a naturally occurring antioxidant known for its role in immune response and cellular detoxification, is the target of various proinflammatory cytokines and transcription factors resulting in the infection, replication, and production of reactive oxygen species. This leads to more severe symptoms of COVID-19 and increased susceptibility to other illnesses such as tuberculosis. The emergence of vaccines against COVID-19, usage of monoclonal antibodies as treatments for infection, and implementation of pharmaceutical drugs have been effective methods for preventing and treating symptoms. However, with the mutating nature of the virus, other treatment modalities have been in research. With its role in antiviral defense and immune response, glutathione has been heavily explored in regard to COVID-19. Glutathione has demonstrated protective effects on inflammation and downregulation of reactive oxygen species, thereby resulting in less severe symptoms of COVID-19 infection and warranting the discussion of glutathione as a treatment mechanism.
