Melatonin ameliorates chronic copper-induced lung injury.

Copper (Cu) is an important trace element required for several biological processes. The use of copper is increasing gradually in several applications. Previous studies suggest that excess levels of copper are attributed to induce oxidative stress and inflammation, mediating tissue damage. Inline, melatonin the hormone of darkness has been reported to exhibit various therapeutic effects including strong free radical scavenging properties and anti-inflammatory effects. However, its effects against pulmonary injury promoted by copper are not explored and remain unclear so far. Therefore, the present study was aimed to investigate the protective effect of melatonin against copper-induced lung damage. Female Sprague Dawley (SD) rats were exposed to 250 ppm of copper in drinking water for 16 weeks and treated with melatonin (i.p.) 5 and 10 mg/kg from the week (13-16th). The extent of tissue damage was assessed by tissue oxidative stress parameters, metal estimation and histological analysis. Copper-challenged rats showed altered oxidative stress variables. In addition, metal analysis revealed increased copper accumulation in the lungs and histological staining results further indicated severe tissue injury and inflammatory cell infiltration in copper-exposed rats. To this side, treatment with melatonin showed antioxidant and anti-inflammatory activities evidenced by reduced oxidative stress, tissue inflammation and collagen deposition as compared to copper-exposed animals. Moreover, spectral findings suggested melatonin treatment modulated the frequency sift, as compared to copper-challenged animals. Altogether, the present results suggest that melatonin might play a potential role in preventing copper-induced lung aberrations via inhibiting the ROS-mediated oxidative stress and inflammation.

Targeted Delivery of Montelukast for the Treatment of Alzheimer's Disease.

Alzheimer's Disease (AD) is one of the most common neurodegenerative diseases, which affects millions of people worldwide. Accumulation of amyloid-ß plaques and hyperphosphorylated neurofibrillary tangles are the key mechanisms involved in the etiopathogenesis of AD, characterized by memory loss and behavioural changes. Effective therapies targeting AD pathogenesis are limited, making it the largest unmet clinical need. Unfortunately, the available drugs provide symptomatic relief and primary care, with no substantial impact on the disease pathology. However, in recent years researchers are working hard on several potential therapeutic targets to combat disease pathogenesis, and few drugs have also reached clinical trials. In addition, drugs are being repurposed both in the preclinical and clinical studies for the treatment of AD. For instance, montelukast is the most commonly used leukotriene receptor antagonist for treating asthma and seasonal allergy. Its leukotriene antagonistic action can also be beneficial for the reduction of detrimental effects of leukotriene against neuro-inflammation, a hallmark feature of AD. The available marketed formulations of montelukast present challenges such as poor bioavailability and reduced uptake, reflecting the lack of effectiveness of its desired action in the CNS. While on the other side, targeted drug delivery is a satisfactory approach to surpass the challenges associated with the therapeutic agents. This review will discuss the enhancement of montelukast treatment efficacy and its access to CNS by using new approaches like nano-formulation, nasal gel, solid lipid formulation, nano-structure lipid carrier (NSLC), highlighting lessons learned to target AD pathologies and hurdles that persist.