The silver lining

The silver lining: towards the responsible and limited usage
of silver

Department of Biological Sciences, BITS Pilani K K Birla Goa Campus, Zuarinagar, Goa, India

Silver has attracted much attention as a potent, broad-spectrum, and natural antimicrobial agent since ancient times because of its nontoxic nature to the human body at low concentrations. It treats various infections and ulcers, stores water, and prevents bacterial growth on the surface and within materials. However, there are numerous medical and health benefits of colloidal or nanosilver apart from its microbicidal ability, which the medical community has not fully embraced. These include antiplatelet activity, antioxidant effect, anticancer activity, wound healing, bone regeneration, immunity enhancement, and increase in antibiotic efficiency. Additionally, silver also provides protection against alcohol toxicity, upper respiratory tract infections, and stomach ailments. Although nanosilver has been proposed for various topical applications, its usage by ingestion and inhalation remains controversial due to the lack of detailed and precise toxicity information. These beneficial properties can be utilized by using silver at very low concentrations, which are not harmful to the human body and environment. The following review discusses the diverse medical applications of silver and further recommends human clinical studies for its in vivo usage.

The creation of free radicals and induction of oxidative stress also contributes to the toxicity of AgNPs/ions(Kim et al., 2007; Cao and Liu 2010; Wong and Liu2010). The production of ROS is dependent, to some extent, on the catalytic activity of nanoscale silver. ROS generation is initiated mainly due to the respiratory enzymes and respiratory chain dysfunction (Choi and Hu2008). ROS are generated within or outside of the cell due to cell damage/disruption (Liu et al.2010). Studies using nitrifying bacteria have revealed that the increase in intracellular ROS levels was correlated with the rate of bacterial growth inhibition (Choi and Hu2008). Sustained release of silver ions by AgNPs inside the bacterial cells in an environment with lower pH may create free radicals and induce oxidative stress, thus further enhancing the bactericidal activity (Morones et al.2005; Song et al. 2006)

Genetic material is one of the important target sites, and nanostructured silver was also reported to cause damage to the DNA (Feng et al., 2000; Kim et al., 2010).DNA loses its replication ability once the bacteria are treated with nanosilver. This is due to the capacity of silver ions to bind to the phosphorane residues of DNA molecules (Hatchett and White 1996; Morones et al.2005). This interaction may prevent cell division and may ultimately lead to cell death. Furthermore, silver ions are also reported to affect gene expression. In E. coli, it has been shown that nanosilver denatures the 30S ribosomal subunit by preventing the expression of S2 protein, a component of the ribosomal subunit. Additionally, the expression of genes encoding other proteins and enzymes involved in energy reactions in ATP synthesis was also inhibited (Gogoi et al. 2006)

In the natural world, more than 99% of all bacteria exist as biofilms (Costerton et al1987). Biofilms are the protective structures created by the colonies of pathogens in order to evade the effects of antibiotic drugs. They are protected by an extracellular matrix held together by proteins and polysaccharides commonly referred to as extracellular polymeric substance. This affects the efficiency of the strongest of antibiotics and biofilms can be as much as a thousand times more resistant than planktonic cells. The growth of biofilms is a major problem within the healthcare and food industries. Biofilms can form on many medical implants such as catheters, artificial hips and contact lenses. According to the National Institute of Health more than 60% of all infections are caused by biofilms. These include, but are not limited to endocarditis, cystic fibrosis, otitis media, chronic prostatitis, urinary tract infections, dental plaque infections, gingivitis, periodontitis, chronic sinusitis, burn wound infections and bone infections (Kim 2001).

Many recent studies have demonstrated conclusively that antimicrobial silver can penetrate through the bacterial biofilms to completely destroy them and can even prevent microbes from developing biofilms. As compared to the antibiotics, silver is proposed to be less affected by the micro-environmental variations found in biofilms due to its multimodal mechanism of action (Bjarnsholt et al2007).