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Lartey, N. L.

Publications and source records attributed to Lartey, N. L..

2 recordsLinked to original sources

Acute and sub-chronic toxicity of aqueous stem-bark extract of Annickia polycarpa

Background and aimThe lack of standardization and scientific validation of the use of most plant extracts leads to toxicity problems. The stem bark extract of Annickia polycarpa has been shown to possess antioxidant, antidiabetic, analgesic, and anti-colitis effects. However, nothing is known about the effects of the prolonged use of the extract. Thus, we investigated the acute and sub-chronic toxicity of the aqueous stem bark extract of (APE) in Sprague-Dawley rats. Experimental procedureThe LD50 and sub-chronic toxicity of APE (20 mg/kg, 100 mg/kg, and 500 mg/kg) was studied over 3 months in Sprague-Dawley rats. Serum alkaline phosphatase (ALP), alanine transaminase (ALT), direct bilirubin and creatinine were measured after 3 months of treatment. Hematological analysis and urinalysis were also performed. Also, the effect of APE on blood clotting time and pentobarbital-induced sleeping time were determined at the termination of treatment. Finally, histological analysis was done on liver, kidney, lung, and heart after hematoxylin-eosin staining of tissue cross-sections at the termination of treatment. Results and conclusionThe LD50 of APE in rats was higher than 5000 mg/kg with no observable signs of toxicity. APE also showed no hematotoxic effect when used consistently for 3 months. Additionally, APE had no adverse effect on the liver and kidney evidenced by a lack of effect on serum biochemical parameters (ALP, ALT, direct bilirubin, and creatinine), urinalysis as well as the tissue morphology of these organs. No adverse morphological effects were also observed with the heart muscle cells. However, APE showed mild selective toxicity to the lung characterized by alveolar space closing and interstitial fibrosis and alveolar septa thickening. These results indicate that APE is generally non-toxic at the tested doses but shows mild selective pneumotoxicity when used over a long period of time.

pharmacology and toxicology↗

ADAM17 inhibition prevents neutrophilia and lung injury in a mouse model of Covid-19

Severe coronavirus disease 2019 (Covid-19) is characterized by lung injury, cytokine storm and increased neutrophil-to-lymphocyte ratio (NLR). Current therapies focus on reducing viral replication and inflammatory responses, but no specific treatment exists to prevent the development of severe Covid-19 in infected individuals. Angiotensin-converting enzyme-2 ACE-2) is the receptor for SARS-CoV-2, the virus causing Covid-19, but it is also critical for maintaining the correct functionality of lung epithelium and endothelium. Coronaviruses induce activation of a disintegrin and metalloprotease 17 (ADAM17) and shedding of ACE-2 from the cell surface resulting in exacerbated inflammatory responses. Thus, we hypothesized that ADAM17 inhibition ameliorates Covid-19-related lung inflammation. We employed a pre-clinical mouse model using intra-tracheal instillation of a combination of polyinosinic:polycytidylic acid (poly-I:C) and the receptor-binding domain of the SARS-CoV-2 spike protein (RBD-S) to mimic lung damage associated with Covid-19. Histological analysis of inflamed mice confirmed the expected signs of lung injury including edema, fibrosis, vascular congestion and leukocyte infiltration. Moreover, inflamed mice also showed an increased NLR as observed in critically ill Covid-19 patients. Administration of the ADAM17 inhibitors apratastat and TMI-1 significantly improved lung histology and prevented leukocyte infiltration. Reduced leukocyte recruitment could be explained by reduced production of pro-inflammatory cytokines and lower levels of the endothelial adhesion molecules ICAM-1 and VCAM-1. Additionally, the NLR was significantly reduced by ADAM17 inhibition. Thus, we propose inhibition of ADAM17 as a novel promising treatment strategy in SARS-CoV-2-infected individuals to prevent the progression towards severe Covid-19.

pathology↗