Drinking Water Sources along the Banks of Buriganga River of Bangladesh are Polluted and Possess Serious Health Risks: A Comprehensive In Vivo Analysis.

Background: The river Buriganga, one of the major dumping zones of industrial wastes in Bangladesh, is responsible for contaminating the drinking water sources along its length. This study aimed to assess the water quality from these sources by monitoring the changes in hematological, biochemical, and histological parameters caused in healthy rats due to their consumption. Methods: Using ethylenediaminetetraacetic acid (EDTA) as an anticoagulant agent, hematological and biochemical analyses of Sprague-Dawley rat models were executed in this study. Following blood sampling, the rats were sacrificed, and the heart, lungs, kidneys, liver, and spleen were separated to carry out the histological analysis. Later, to perform the statistical analysis, SPSS, V.25.0 was utilized. Results: A significant rise (p < 0.02) in body weight was recorded due to increased protein synthesis, inflammations; increased lymphocyte, white blood cell (WBC), and neutrophil count but hemoglobin (20.0 ± 1.39 g/dL vs. 15.25 ± 0.36 g/dL; p) and red blood cell (RBC) count ((6.24 ± 0.45) × 106/µL vs. (5.47 ± 0.34) × 106/µL)) decreased due to infections and hematopoietic stem cell poisoning by pathogens in water samples. Elevated (p < 0.01) serum urea, creatinine, alanine, and aspartate aminotransferase levels indicated kidney malfunction and hepatic tissue necrosis. Histological analysis revealed gross lesions, internal hemorrhages in the brain; inflammations, granulomas, migrating macrophages in the spleen; fibrosis (resulting in hypo-perfusion), and collagen formation in cardiac muscles. Conclusions: The findings in this study provide comprehensive evidence, based on in vivo analysis, that the water bodies around the Buriganga river are likely to be contaminated with toxic chemicals and microbial entities making them unfit for human consumption.

Targeting the P2Y13 Receptor Suppresses IL-33 and HMGB1 Release and Ameliorates Experimental Asthma.

Rationale: The alarmins IL-33 and HMGB1 (high mobility group box 1) contribute to type 2 inflammation and asthma pathogenesis. Objectives: To determine whether P2Y13-R (P2Y13 receptor), a purinergic GPCR (G protein-coupled receptor) and risk allele for asthma, regulates the release of IL-33 and HMGB1. Methods: Bronchial biopsy specimens were obtained from healthy subjects and subjects with asthma. Primary human airway epithelial cells (AECs), primary mouse AECs, or C57Bl/6 mice were inoculated with various aeroallergens or respiratory viruses, and the nuclear-to-cytoplasmic translocation and release of alarmins was measured by using immunohistochemistry and an ELISA. The role of P2Y13-R in AEC function and in the onset, progression, and exacerbation of experimental asthma was assessed by using pharmacological antagonists and mice with P2Y13-R gene deletion. Measurements and Main Results: Aeroallergen exposure induced the extracellular release of ADP and ATP, nucleotides that activate P2Y13-R. ATP, ADP, and aeroallergen (house dust mite, cockroach, or Alternaria antigen) or virus exposure induced the nuclear-to-cytoplasmic translocation and subsequent release of IL-33 and HMGB1, and this response was ablated by genetic deletion or pharmacological antagonism of P2Y13. In mice, prophylactic or therapeutic P2Y13-R blockade attenuated asthma onset and, critically, ablated the severity of a rhinovirus-associated exacerbation in a high-fidelity experimental model of chronic asthma. Moreover, P2Y13-R antagonism derepressed antiviral immunity, increasing IFN-λ production and decreasing viral copies in the lung. Conclusions: We identify P2Y13-R as a novel gatekeeper of the nuclear alarmins IL-33 and HMGB1 and demonstrate that the targeting of this GPCR via genetic deletion or treatment with a small-molecule antagonist protects against the onset and exacerbations of experimental asthma.