Phosphodiesterase-5 (PDE-5) Inhibitors as Emergent Environmental Contaminants: Advanced Remediation and Analytical Methods

Abstract

Pharmaceuticals, fundamental in therapy and the prevention of known pathologies, are responsible for environmental pollution. These substances, called “emerging contaminants,” are harmful to human health because they enter the environment in quantities exceeding the natural self-capacity purification of the ecosystems. Furthermore, wastewater treatment plants (WWTPs) cannot remove these substances, which can undergo chemical/biological transformations in the environment, thus forming by-products, sometimes more toxic than the parent molecules; successively, they move into rivers and could reach the drinking water supplies. All these phenomena represent a severe public health problem. Therefore, the Water Framework Directive by European Union imposed the monitoring of drugs’ levels in aqueous matrices. Every two years, the EU carefully updates the list of potential water pollutants, called the Watch List, including pharmaceuticals, to evaluate their risk on the aquatic environment. The last Commission Implementing Decision (EU 2018/840) comprises several substances of primary concern. In addition, the scientific community is giving particular attention to other pharmaceuticals not yet on the Watch list, whose markets are in growth; particularly, the Phosphodiesterase 5 (PDE-5) inhibitors used for the pharmaceutical treatment of erectile dysfunction (ED) in men. This review discusses the presence of PDE-5 inhibitors in environmental systems, their toxic effects, the different kinds of removal, and the analytical methods normally adopted for their detection. In addition, the study helps figure out the best possible strategy to tackle pharmaceutical pollution by using analytical and advanced diagnostic methods.

Single and combined toxicity of tadalafil (Cilais) and microplastic in Tilapia fish (Oreochromis niloticus)

“…The dosage of tadalafil employed in our study was chosen based on previous research 21 . However, a study by Bianco et al [ 21 ] indicated that there is no human health risk for exposure to sildenafil (LC50 = 42.74 for B. calyciflorus ) and tadalafil (LC50 = no effect up to 20 for B. calyciflorus ). However, they require special care as this form of contamination is found in any aquatic system evaluated.…”

“…One hundred and twenty fish ( O. niloticus) were selected and divided into four treatments, each treatment contains 30 fish in triplicates (as 10 fish for each) in 96L glass aquarium water. The fish were distributed into 1st group control group (fish exposed to only water); 2nd group exposed to 10 mg/LPE-MPs 15 ; 3rd group exposed to 20 mg/l tadalafil (Cilais) 21 ; 4th group exposed to 20 mg/l tadalafil (Cilais) + 10 mg/LPE-MPs. Twelve fish from each group were chosen at random after 15 days of exposure and put unconscious with crushed ice 36 .…”

“…Later, it is utilized to treat asthma and sexual dysfunction 23 . Tadalafil, an emerging polluter, might be eliminated in stool or urine and carried through sewers to public wastewater treatment facilities alongside other pharmaceutical drugs 21 . Despite the fact that the freshwater rotifer (Brachionus calyciflorus) was not acutely adversely affected by tadalafil up to the highest dosage (20 mg L −1 ).Few studies have explored sildenafil residues in the environment using multi-residue approaches [24][25][26] , and even fewer have measured tadalafil and vardenafil residues or included their metabolic products 27,28 .…”

“…These contaminants may enter the environment at rates greater than the ecosystems' inherent capability for detoxification 20 . Furthermore, sewage treatment facilities were unable to eradicate these compounds because they may convert to metabolic by-products that were frequently more dangerous than the original compounds; as a result, they entered rivers and could spread into drinking water sources 21 .…”

Determination of Five Phosphodiesterase-5 Inhibitors in Multiple Honey-Based Consumer Products by Chromatographic Technique in Rat Plasma

“…Multiple studies have shown that ED results from cardiovascular diseases and other health problems, such as smoking, high blood pressure, high cholesterol, metabolic syndrome, and diabetes. However, it can also be caused by (i) neurological (deficit in nerve signaling to the "corpora cavernosa"), (ii) psychological (depression, stress, or anxiety), or (iii) endocrinologic (low testosterone levels or other hormone imbalances) factors [6][7][8][9]. Several PDE5Is are currently on the market, including the FDA-approved medications sildenafil, vardenafil, tadalafil, and avanafil, as well as the non-FDA-approved medications lodenafil, udenafil, and mirodenafil [10].…”