Paeonol Reverses Adriamycin Induced Cardiac Pathological Remodeling through Notch1 Signaling Reactivation in H9c2 Cells and Adult Zebrafish Heart.

Adriamycin is a commonly prescribed chemotherapeutic drug for a wide range of cancers. Adriamycin causes cardiotoxicity as an adverse effect that limits its clinical application in cancer treatment. Several mechanisms have been proposed to explain the toxicity it causes in heart cells. Disruption of inherent cardiac repair mechanism is the least understood mechanism of Adriamycin-induced cardiotoxicity. Adriamycin induces pathological remodeling in cardiac cells by promoting apoptosis, hypertrophy, and fibrosis. We found that Adriamycin inhibited Notch1 in a time- and dose-dependent manner in H9c2 cells. We used Paeonol, a Notch1 activator, and analyzed the markers of apoptosis, hypertrophy, and fibrosis in H9c2 cells in vitro and in adult zebrafish heart in vivo as model systems to study Adriamycin-induced cardiotoxicity. Paeonol activated Notch1 signaling and expression of its downstream target genes effectively in the Adriamycin-treated condition in vitro and in vivo. Also we detected that Notch activation using Paeonol protected the cells from apoptosis, collagen deposition, and hypertrophy response using functional assays. We conclude that Adriamycin induced cardiotoxicity by promoting the pathological cardiac remodeling through inhibition of Notch1 signaling and that the Notch1 reactivation by Paeonol protected the cells and reversed the cardiotoxicity.

Occurrence, spatial and seasonal variations of emerging contaminants in the aquatic environment of Sharjah, United Arab Emirates.

The occurrence, seasonal variations and spatial distribution of emerging contaminants (ECs) in wastewater effluents from wastewater treatment plant (WWTP) and UAE's receiving coastal aquatic environment (seawater and sediments) were evaluated in the present study. A total of 21, 23, and 22 contaminants in the effluents, seawater, and sediments, respectively, at concentrations ranging from low ng L-1 up to 1782 ng L-1 in effluents, from low ng/l up to 236.10 ng L-1 in seawater, and from low ng g-1 up to 60.15 ng g-1 in sediments were recorded. The study revealed that imidacloprid, thiabendazole, and acetaminophen were the most ubiquitous compounds in effluents, seawater, and sediments, respectively, since they were found in all samples collected with a detection frequency of 100%. The study also revealed that the higher concentrations of most contaminants were recorded in autumn. However, thiabendazole in effluents and seawater, acetamiprid in effluents, and sulphapyridine in seawater and sediments showed a higher load in winter. This study highlights the need for proper monitoring and management of ECs in wastewater effluents, seawater, and sediments, especially during the autumn and winter seasons, to minimize their impact on the marine ecosystem and public health.