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Jan 2024 DOI 10.14302/issn.2328-0182.japst-23-4771
Tariku Belay YilkalCorresponding author
Background Immunoglobulins are bio-receptors found embedded in the cell membrane with a biological role that detects the harmful molecules of a test compound. These bio-receptors interface between a biological system and its external environment that transduce information to the effector via intermediate messengers in which its response efficiency usually exhausts at high doses of exposure to external stimuli. The purpose of this review article is, therefore, to elaborate on the computational method for systemic biology which was designed to convert qualitative pharmacological data into the quantitative one that might help to determine the toxicity of a test compound. Methods First, acute toxicity studies using different levels of doses prepared from each test compound have been conducted on Balb c mice. Then, blood specimens from the tail and facial veins of each sampled Balb c mouse were collected 3 days before dosing as a reference test and 4 hr after dosing for comparison. The changes in the efficiency of immunoglobulins immune response (ΔIg) after dosing were determined using quantitative immunoassay and the body’s response against the dose as the toxic reaction rate (r) and the toxic severity (s) were finally determined using computational methods as r=d/t-ΔIg mg/sec and (s=r/w×100) %/sec respectively, where (w) represents the body weight of a study animal, (t) represents the period of time at which undesirable bio-physiological responses manifested on treated study animals and (ΔIg) represents the changes in the concentration of immunoglobulins in blood serum after dosing. Results The results of different studies revealed that the dose has never limited the toxic property of a test compound but the length of time at which the undesirable side effect was manifested on study animals. The period of time at which adverse effects manifested on treated Balb c mice was inversely related to the amount of dose administered in the oral route. The higher the dose of the administered test compound, the shorter the period of time at which the undesirable side effect was manifested on treated Balb c mice. This means that the adverse effect of test compounds was not because of the dose but rather due to its toxic reaction rate which ultimately determined the toxic severity in the natural process of treated Balb c mice. Balb c mice treated with a dose whose toxic reaction rate was ≤ 0 survived from death whereas Balb c mice treated with a dose that had a toxic reaction rate of > 0 died at different lengths of time after dosing depending on the toxic severity of a test compound. It could be a scientific fact to declare that a test compound is safe when the toxic reaction rate (r) and toxic severity (s) of a dose is ≤ 0 and toxic when it is > 0 in the natural processes of a study animal.
Mar 2023 DOI 10.14302/issn.2474-7785.jarh-22-4381
Tariku Belay YilkalCorresponding author
Background Ageing is a life process in which progressive molecular, cellular, physiological and anatomical changes manifesting in humans and animals including other organisms lead to the decline of biological functions. Immunoglobulins (Igs) are glycoprotein molecules produced by white blood cells mainly B lymphocytes following signal transduction as a result of their interaction with pathogenic microbes or poisonous substances introduced into the body systems. They elicit responses against the side effects of pathogens and poisons in which their response efficiency usually declines as we are ageing. Objective Thus, the similarities between Igs’ immune response against the different amounts of xenobiotics and the biological changes associated with ageing have been systematically assessed using the reports of different study results on humans and animals. Methods First, a literature search was carried out in google, PubMed and google scholar using planned search terms related to the title of this study. Review and original articles were retrieved, downloaded and saved on a computer. And then the effects of different factors i.e. xenobiotics, age, sex and lifestyle-based practices on the levels of serum Igs (IgG, IgA and IgM) in animals and humans have been studied using a systematic review of different literature sources. Finally, the relationship between the findings of various studies has been assessed and judgment on the possible cause of ageing has been made. Results The findings of different research have demonstrated that the signaling efficiency of immunoglobulin M (IgM) has been limited by the amount of test compounds administered to study Balb c mice in the oral route. The response efficiency of IgM immune response against the lower doses of test compounds were high compared to the higher doses of test compounds which was low. The results of different other studies also demonstrated that the decline of serum IgM levels was associated with ageing. The relationship between alcohol consumption and the concentration of serum Igs was also described in the report of different studies. These studies have shown that there was lower level of IgG in the blood serum of alcohol consumers compared to non-consumers. The study has also demonstrated a lower level of serum IgM with higher alcohol consumption and higher serum concentration with moderate beer consumption. Conclusion The trajectory of Igs’ immune response against different amounts of xenobiotics was highly associated with the trajectory of biological changes during ageing. These research findings might be the possible evidence to conclude that ageing is caused by the foodstuffs and non-foodstuffs we usually consume, the lifestyles we usually experience and the way of life we usually live in the environment which gradually defiling the natural processes of the body.
Jun 2022 DOI 10.14302/issn.2328-0182.japst-22-4193
Tariku Belay YilkalCorresponding author
School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda
The strategy for safe drug discovery and development has limited clinical success as compared to wasted time and resources annually. This is due to the fact that the results of multiphase preclinical trials are less likely to make an accurate early prediction on the safety of test compounds to progress into the clinic as a valuable therapeutic agent. A lot of time and resources has been wasted in the multistage processes of drug discovery and development that does not work at the end of the procedure every year. During pre-marketing stage, for instance, the number of unsuccessful clinical trials are greater than the successful one because of safety issues. A toxicity study at different stages of preclinical and clinical trials is a routine procedure to investigate the undesirable side effects of test compounds being manifested on the natural processes of living things. It deals with the effect and mechanism of toxicity of test compounds that triggers different biological responses on different organ systems. The biological responses that would be manifested as a result of interaction between the receptors and active molecules of a test compound could be desirable pharmacological effect or undesirable side effect or both responses are manifested simultaneously depending on the selectivity or specificity of the molecule of a test compound for its receptor subtype which makes safe drug discovery and development very challenging. The response efficiency of the body (the net outcome of the body’s biological reaction against the side effect) would determine the potency of a test compound to manifest undesirable pharmacologic effect. In other words, the amount of a drug required to cause a biological harm or injury depends on the magnitude of the body’s biological reaction in which the immune response plays a great pharmacological role by neutralizing and harmonizing xenobiotics with the biological molecules. The dose of a test compound at 100 mg/kg body weight, for instance, could be lethal to some of the study animals while it is still non-lethal to some other study animals depending on the response efficiency of the body. The immune system is well connected to each and every biological systems of the body which allows it to detect undesirable side effects being manifested through immunoglobulins signalling and activation mechanisms. This complex communication network helps to localize the diverse side effects of a test compound being manifested on different organ systems into the immune system which makes a toxicity study relatively simple to monitor. The cellular immune system becomes active following the molecule-receptor interaction and start producing antibodies which is also known as immunoglobulins to protect bodily harm and destruction. Under normal biological circumstances, the amount of immunoglobulins produced by the cellular immune system following exposure to a test compound is proportional to the number of harmful molecules interacted with its receptor subtype. Thus, with the reference to the changes in the immune response against the administered dose, it would be able to deal with the diverse undesirable side effects of a test compound being manifested on treated study animals using computational systemic biology.