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  • Acetaminophen N acetyl p aminophenol AAP Fig is a

    2024-11-12

    Acetaminophen (N-acetyl-p-aminophenol, AAP) (Fig. 1) is a medically important, low cost, readily available and commonly used over the counter analgesic and antipyretic drug [18,19]. Acetaminophen monotherapy is efficient and is safer than Aspirin and Ibuprofen [20]. The efficacy and tolerability in individual condition is warranted [18]. The mechanism of analgesic action of acetaminophen is complex and its action of medicament has not been completely understood [20]. At therapeutic doses, acetaminophen is safe drug but not devoid of side effects [18] and suggest the possibility of acetaminophen exerting other specific biological effects [21]. High dosages, in humans and experimental animals, lead to necrosis, nephrotoxicity, and extra hepatic lesions [22]. Nevertheless, it is grossly abused in Nigeria and it has been blamed for the rising cases of SF1670 attacks, stroke and early death [23,24]. The negative effect of Acetaminophen on the antioxidant defense enzyme system has been documented [23]. The interaction of acetaminophen with Human Serum Albumin (HSA) was previously investigated [25]. The authors detailed the biochemical and biophysical data illustrating the relevance of HSA to the acetaminophen pharmacokinetics. However, in a pathogenic state of human serum albumin, lower albumin concentration and weaker drug–protein interaction can result in the increase of drug concentration in the blood and lead to toxicity [26,27]. More worrisome, is the use of acetaminophen with alcoholic beverages [21,28]. The link between Aldehyde dehydrogenase and Acetaminophen metabolism is becoming increasingly imaginable [7,21]. ALDH has been identified as a major acetaminophen-binding protein [28]; and was down regulated in mouse liver exposed to high dosage of acetaminophen [29]. However, the affinity and interaction mechanism of acetaminophen to ALDH still remain uncharted. The effect of the complexation on ALDH structure and conformation is yet to be elucidated. Several spectroscopic techniques, as powerful tools, have been used to study the interaction between drugs and proteins. They allow non-intrusive measurements of substances in low concentration under physiological conditions [30]. Fluorescence technique is the simplest method to study the interaction of drugs/ligands and bio-macromolecules because it has the advantage of high sensitivity, rapidity and ease of implementation [31,32]. It is an important method to sense changes in the local microenvironment of fluorescent chromophore [33] and help understand the biopolymer's binding mechanisms to drugs and provide clues to the nature of the binding phenomenon [34,35]. The information on the acetaminophen-ALDH binding mode, the binding constant and the effects of acetaminophen complexation on the protein structure is obscured. In the present work, the binding of Acetaminophen to ALDH was studied under physiological conditions by spectroscopic techniques. The quenching mechanism between Acetaminophen and ALDH with regards stoichiometric and thermodynamic of ligand binding and consequently the effect on the protein conformation were investigated at molecular level. In addition, the effects of pH and viscosity of Acetaminophen -ALDH complex were also examined. All these were complimented by in silico analysis and molecular docking.
    Materials and methods
    Results and discussion
    Conclusions
    Acknowledgments This work is supported by the TETFund Research Grant of the Senate of The Federal University of Technology, Akure. The author thanked IFS for the funds (F/4449 1F and F/4449-2F) used to purchase the equipments used and CCMB, Hyderabad, India for the use of their CD during his stay in the institute. The effort of Dr. Olusola Elekofehinti is highly regarded in the docking experiment.
    Introduction A central problem in hematology is the limited lifespan of mature non-lymphoid cells, which necessitates constant production of new blood cells. In humans, the estimated lifespan of circulating red blood cells (RBCs) is 120days, polymorphonuclear neutrophils (PMNs) 2days, and platelets 5–10days. To maintain the blood system, approximately 2×1011 RBCs, 1.6×1011 PMNs, and 1011 platelets are produced daily [1–4]. The evolutionary resolution of this problem in mammals is based on a hierarchy of self-renewing multipotent hematopoietic stem cells (HSC), which give rise to non-self-renewing, lineage committed hematopoietic progenitor cells (HPC) capable of massive expansion and differentiation into mature blood cells.