Leukotrienes vs. Montelukast-Activity, Metabolism, and Toxicity Hints for Repurposing.

Increasing environmental distress is associated with a growing asthma incidence; no treatments are available but montelukast (MTK)-an antagonist of the cysteinyl leukotrienes receptor 1-is widely used in the management of symptoms among adults and children. Recently, new molecular targets have been identified and MTK has been proposed for repurposing in other therapeutic applications, with several ongoing clinical trials. The proposed applications include neuroinflammation control, which could be explored in some neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases (AD and PD). However, this drug has been associated with an increasing number of reported neuropsychiatric adverse drug reactions (ADRs). Besides, and despite being on the market since 1998, MTK metabolism is still poorly understood and the mechanisms underlying neuropsychiatric ADRs remain unknown. We review the role of MTK as a modulator of leukotriene pathways and systematize the current knowledge about MTK metabolism. Known toxic effects of MTK are discussed, and repurposing applications are presented comprehensively, with a focus on AD and PD.

Antioxidative response of lettuce (Lactuca sativa) to carbamazepine-induced stress.

Carbamazepine (CBZ) is a widely used anti-epileptic drug that has been detected in wastewaters from sewage treating plants and thus appears in rivers, streams and other water bodies. As plants can absorb this compound, it can also appear in edible plants like lettuce, entering the food chain. In this study, the effect of carbamazepine in lettuce plants grown in hydroponic solution is analyzed. CBZ was detected both in roots and in leaves and is shown to induce oxidative stress. Hydrogen peroxide levels increased both in leaves and in roots while malondialdehyde increased only in leaves. Regarding the activity of antioxidative enzymes in the leaves, it is shown that superoxide dismutase (SOD), catalase (CAT), guaiacol peroxidase (GPOD) and ascorbate peroxidase (APX) have a relevant role in quenching reactive oxygen species induced by oxidative stress. In roots, the only enzymes that showed increased activity were CAT, GPOD and glutathione reductase (GR). Ascorbate and glutathione also appear to have an important role as antioxidants in response to increased concentrations of carbamazepine. Although the roots are in direct contact with the contaminant, the leaves showed the strongest oxidative effects.