Over-the-Counter Monocyclic Non-Steroidal Anti-Inflammatory Drugs in Environment—Sources, Risks, Biodegradation

Abstract

Recently, the increased use of monocyclic non-steroidal anti-inflammatory drugs has resulted in their presence in the environment. This may have potential negative effects on living organisms. The biotransformation mechanisms of monocyclic non-steroidal anti-inflammatory drugs in the human body and in other mammals occur by hydroxylation and conjugation with glycine or glucuronic acid. Biotransformation/biodegradation of monocyclic non-steroidal anti-inflammatory drugs in the environment may be caused by fungal or bacterial microorganisms. Salicylic acid derivatives are degraded by catechol or gentisate as intermediates which are cleaved by dioxygenases. The key intermediate of the paracetamol degradation pathways is hydroquinone. Sometimes, after hydrolysis of this drug, 4-aminophenol is formed, which is a dead-end metabolite. Ibuprofen is metabolized by hydroxylation or activation with CoA, resulting in the formation of isobutylocatechol. The aim of this work is to attempt to summarize the knowledge about environmental risk connected with the presence of over-the-counter anti-inflammatory drugs, their sources and the biotransformation and/or biodegradation pathways of these drugs.

Organic micropollutants paracetamol and ibuprofen—toxicity, biodegradation, and genetic background of their utilization by bacteria

“…In the UK, paracetamol is classified in the top three of the most frequently prescribed drugs. In the USA, where paracetamol is one of the 200 most frequently used pharmaceuticals its consumption during 2001–2005 reached about 29 billion doses (Li et al 2014 ; Marchlewicz et al 2015 ). Prevalent occurrence of paracetamol, as well as its main degradation product (4-aminophenol) in the environment, is also partly associated with their use for manufacturing of azo dyes and photographic materials (Zhang et al 2013 ).…”

“…Ibuprofen (abbreviated as IBU, 2-(4-methylpropyl)phenyl)propanoic acid) currently is the third most popular NSAID worldwide. The annual consumption of ibuprofen in selected EU countries is about 300 t in Germany, 162 t in the UK, and 58 t in Poland (Marchlewicz et al 2015 ). In recent years, increasing intake of ibuprofen was reported for Slovakia, Czech Republic, and Finland.…”

“…In human body, up to 15% of ibuprofen is excreted as an unchanged form or glucuronide and thiol conjugates or as metabolites, i.e., hydroxyibuprofen (mostly 2-OH and 3-OH, 1-OH is a minor product), carboxyibuprofen, and carboxyhydratropic acid, which have no apparent pharmacological activity. Nevertheless, conjugates of ibuprofen with glucuronides may be hydrolyzed in the environment (Marchlewicz et al 2015 ; Murdoch and Hay 2015 ). Ibuprofen has been found at different concentrations in environmental samples, e.g., in wastewater from 45 μg/L in Canada (Guerra et al 2014 ) to 703–1673 μg/L in Pakistan, 1.38 μg/L in South Africa, and 5.78 μg/L in Belgium (Vergeynst et al 2015 ; Ashfaq et al 2017a ), in sludge from 0.009 μg/kg for South Africa (Matongo et al 2015 ) to 2053–6064 μg/kg in Pakistan.…”

“…A wide range of unique emerging pollutants, including pharmaceuticals and their metabolites or residues, are continuously introduced into various environments mainly from hospital and municipal wastewater, consumer use, or disposal and discharges from pharmaceutical production (Hu et al 2013 ; Zhang et al 2013 ; Ebele et al 2017 ). Drugs that reach the environment are mainly excreted in unmodified or slightly metabolized form, i.e., hydroxylated or conjugated with charged molecules such as glutathione, glucuronic acid, or sulfate (Marchlewicz et al 2015 ). To date, wastewater treatment plants (WWTPs) are not designed to completely remove this kind of organic micropollutants, often characterized by high water solubility and poor biodegradability, which favor their environmental persistence (Candido et al 2017 ).…”

Putative Role of Flavobacterium, Dokdonella and Methylophilus Strains in Paracetamol Biodegradation

“…However, there is a lack of information about the environmental behavior of the human metabolites of paracetamol and respective transformation products resulting from their physicochemical and microbial removal in sewage treatment facilities (Peake et al 2016). Yet, given that these metabolites can be persistent and some are even more toxic than the parent compound, it is essential to determine their fate in biological systems (Wu et al 2012;Marchlewicz et al 2015;Peake et al 2016;Torun et al 2015;Mbokou et al 2016) and, hence, to search for new and effective ways to degrade or remove them from wastewater and resulting treated effluents. In this regard, biodegradation may represent a low-cost effective solution (Wu et al 2012), though several advanced oxidation processes have also been extensively studied for the degradation of paracetamol (e.g.…”