Pharmacology and Toxicology
Doha Ismail Alrawi; Musab Mohammed Khalaf; Mohammed Khalid Jamaludeen
Abstract
Background: Exposure to both synthetic and naturally occurring chemical substances can cause a wide range of reactions such as Drug-Induced Liver Injury(DILI). It is a serious problem due to the increasing number of substances being used for the treatment of different illnesses, coupled with the growing ...
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Background: Exposure to both synthetic and naturally occurring chemical substances can cause a wide range of reactions such as Drug-Induced Liver Injury(DILI). It is a serious problem due to the increasing number of substances being used for the treatment of different illnesses, coupled with the growing popularity of herbal products encourage self-medication but are not strictly regulated. It can be challenging to predict, diagnose, and treat (DILI) due to the wide range of underlying mechanisms and risk factors. DILI can range in severity from moderate transaminase elevation to potentially fatal acute liver failure. Aim: The purpose of this review article is to gain a better understanding of DILI , which includes its causes, classification, the more toxic medications, and chemicals that can lead to DILI. The purpose also covers the biomarkers and liver function tests that can help identify this condition, as well as the substances that are commonly used for liver protection. Methods: We made a worldwide search through well-known online databases such as PubMed, Science Direct, Elsevier, and others to keep going with related liver disease trials that have been approved in previous years. Conclusion: DILI is one of the leading causes of liver disease globally, resulting from the use of prescription, over-the-counter, and herbal medications. Due to the lack of a single clinical, laboratory, or histologic characteristic specific to the illness, diagnosing DILI can be challenging.For an accurate diagnosis, it is essential to establish a causal correlation between the suspected substances and other causes of liver injury.
Pharmacology and Toxicology
khalil Amjad Hadid; Fawaz A. Alassaf; Mohammed Najim Abed
Abstract
Background: Chronic inflammation is responsible for low insulin sensitivity, making obesity a major risk factor for developing insulin resistance, type 2 diabetes mellitus, and metabolic syndrome. Increased expression of inflammatory cytokines activates several signaling pathways, consequently leading ...
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Background: Chronic inflammation is responsible for low insulin sensitivity, making obesity a major risk factor for developing insulin resistance, type 2 diabetes mellitus, and metabolic syndrome. Increased expression of inflammatory cytokines activates several signaling pathways, consequently leading to the accumulation of fats in adipocytes and contributing to the pathogenesis of insulin resistance. Aim: The review aimed to provide an overview of the potential molecular correlation between the insulin signaling pathway and the inflammatory process in addition to their linkage to the development of insulin resistance and other metabolic diseases, with an exploration of the possibility of using drugs that target inflammation in the management of diabetes. Results: Based on the obtained data from the latest literature, the source of cytokines in insulin-resistant states is the insulin targets themselves including the adipose tissue and liver, but to a greater extent the activated macrophages. Prolonged inflammation in these tissues may result in systemic insulin resistance via endocrine signaling and localized insulin resistance by paracrine/autocrine cytokine signaling. Conclusion: Inflammation is involved in the pathogenesis of insulin resistance and diabetes type 2, consequently, in the management of insulin resistance, anti-inflammatory agents may benefit, and the risk assessment may benefit from the use of inflammatory biomarkers in such disorders.
Pharmacology and Toxicology
Abdulnaser Ahmad Ali; Musab Mohammed Khalaf; Abdulla A. Ahmad
Abstract
Background: The prevention of drug-induced cardiotoxicity is a complicated challenge facing healthcare providers during the last few decades. This challenge is raised from the unclear definition of the term “cardiotoxicity”, the overlapping of the symptoms of heart dysfunction due to the ...
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Background: The prevention of drug-induced cardiotoxicity is a complicated challenge facing healthcare providers during the last few decades. This challenge is raised from the unclear definition of the term “cardiotoxicity”, the overlapping of the symptoms of heart dysfunction due to the underlying diseases and the used drugs or using a combination of drugs which makes it difficult to distinguish between the side effects of each drug. Objective: This review discusses the most causative agents of cardiotoxicity, and their mechanisms to induce cardiac muscle damage, and finally focuses on the most applicable methods to deal with these dangerous heart problems. Methods: The search method involved electronic databases, including PubMed, Web of Science, Springer, Google Scholar, and others to resume relevant trials of heart disease published in the period between 2010-2023. Conclusion: Cardiotoxicity is a common substantial adverse effect of many drugs including anticancer drugs and others. The prevention methods may include medications, such as (Enalapril or carvedilol), supplementation with antioxidants, or cardioprotective natural products.
Pharmacology and Toxicology
Hodhaifa Abdul Mohsin; Mohannad E Qazzaz; Mohanad Alfahad
Abstract
Introduction: Doxorubicin (Dox.) is a very effective antineoplastic agent for treating various tumours. It produces an anti-cancer mechanism through the intercalation of DNA and reducing topoisomerase II enzyme activity in fast-proliferating cancers. However, Dox. is associated with limited-use adverse ...
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Introduction: Doxorubicin (Dox.) is a very effective antineoplastic agent for treating various tumours. It produces an anti-cancer mechanism through the intercalation of DNA and reducing topoisomerase II enzyme activity in fast-proliferating cancers. However, Dox. is associated with limited-use adverse effects specifically accumulative and dose-dependent heart toxicity which is the underlying cause for increasing the risk of mortality in cancer patients that use this kind of anticancer. Results: Many related mechanisms have been suggested for Dox.-induced cardiac toxicity such as oxidative stress and deteriorated mitochondrial function, a disturbance in iron regulatory protein [(IRP)-1], the release of nitric oxide, autophagy and dysregulation of Ca2+ level. Unfortunately, there is no clinically approved protective agent against Dox.-induced cardiotoxicity has been discovered yet. Aim: The current review attempts to focus on collecting information related to the mechanism of stimulating heart disease resulting from the use of Dox. and trying to understand it at the molecular level and addressing the most important compounds, especially the natural ones, and their proposed mechanism of action against Dox.-induced heart toxicity. Conclusion: Dox. still one of the most effective anticancer medications. Due to its undesirable cardiotoxicity and the lack of effective preventative methods, Dox. uses could increase the risk of death and restrict its potential clinical applications. Many mechanisms have been implicated in Dox.-induced cardiac toxicity. Therefore, targeting this alteration using bee propolis has shown strong protective effects against the cardiotoxicity of Dox. and the decrease the death rate among patients suffering from cancer.
Pharmacology and Toxicology
Doaa Khalid Ibrahim; Nooralhuda Akram Yahya
Abstract
Background: Diabetes mellitus is a common metabolic disorder characterized by chronic high blood sugar levels due to impaired insulin secretion or action. Existing diabetic medications have limitations, including high costs and the risk of hypoglycemia. Aim: To overcome these challenges, researchers ...
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Background: Diabetes mellitus is a common metabolic disorder characterized by chronic high blood sugar levels due to impaired insulin secretion or action. Existing diabetic medications have limitations, including high costs and the risk of hypoglycemia. Aim: To overcome these challenges, researchers are exploring advanced treatments, and one potential path is studying plants and natural sources. Many plants include green tea (Camellia sinensis), rich in catechin derivatives, particularly epigallocatechin-3-gallate (EGCG), have shown promising effect because this agent may enhance beta cell proliferation, so it can produce dramatic response in management of diabetes mellitus and it is expected to reduce complication of this disease. Thorough data searching from September 2021 to June 2023 was used to conduct this study. The key terms diabetes mellitus, herbal treatment of diabetes, DYRK1A inhibitor, Epigallocatechin-3-gallate, and beta cell proliferation were concomitantly searched in Google Scholar, Web of Science, and PubMed in order to find relevant material. The publications that are presented here were published between 2014 and 2023. Conclusion: Collectively EGCG properties as a DYRK1A inhibitor may enhance β cell proliferation that is promising effects in diabetes mellitus treatment.
Pharmacology and Toxicology
Dilgash A Abdullah; Hani Almukhtar
Abstract
Background: Statins have demonstrated various beneficial clinical outcomes, not only in patients with elevated cholesterol levels but also in those with normal levels, a collective phenomenon known as pleiotropic effects. In the cardiovascular system, statins exhibit numerous pleiotropic effects, including ...
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Background: Statins have demonstrated various beneficial clinical outcomes, not only in patients with elevated cholesterol levels but also in those with normal levels, a collective phenomenon known as pleiotropic effects. In the cardiovascular system, statins exhibit numerous pleiotropic effects, including the improvement of endothelial function by enhancing nitric oxide synthesis, anti-inflammatory actions, and antioxidant properties. Similarly, within the gastrointestinal tract, statins confer advantageous pleiotropic effects. Aim: This review delves into the potential mechanisms underpinning the gastroprotective impact of statins against indomethacin-induced gastric ulcers. In particular, the administration of statins resulted in a notable elevation in the levels of NO and PGE2 in the mucosa of the stomach. These results substantiate the gastroprotective role of statin is attributed to scavenging of free radicals, elevation of nitric oxide levels, and enhancement of prostaglandin E2 levels. Conclusion: To sum up, the results indicate that statins could be a preferable therapeutic choice for individuals who are susceptible to developing gastric ulcers as a result of NSAIDs usage.
Pharmacology and Toxicology
Rahma Saadaldain Almallah; Hani Almukhtar
Abstract
Background: Mirabegron operates through a distinct mechanism compared to antimuscarinic agents. Its activation of β3-adrenoceptors results in the relaxation of the bladder during the filling phase of micturition. The activation of β3-adrenoceptors, which are connected to Gs-proteins, is hypothesized ...
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Background: Mirabegron operates through a distinct mechanism compared to antimuscarinic agents. Its activation of β3-adrenoceptors results in the relaxation of the bladder during the filling phase of micturition. The activation of β3-adrenoceptors, which are connected to Gs-proteins, is hypothesized to be the mechanism of mirabegron-induced smooth muscle relaxation. This coupling stimulates adenylyl cyclase, leading to an elevation of intracellular levels of cyclic adenosine monophosphate (cAMP). However, in rat and human corpus cavernosum, mirabegron induces relaxation through distinct mechanisms independently through the nitric oxide/cyclic guanosine monophosphate (NO-cGMP) pathway. Consequently, the precise mechanism by which mirabegron enhances relaxation is still not fully known. Aim: The main goal is to delve deeper into the complex mechanisms by which mirabegron causes smooth muscle relaxation in many tissues. Conclusion: Mirabegron and similar β3-adrenoceptor agonists hold promise for treating not only overactive bladder but also a range of other conditions including heart failure and metabolic disorders.
Pharmacology and Toxicology
Teeba H. Sagban; Ausama Ayob Jaccob; Abdulla Ayob Yaqoub; Huda Khadim
Abstract
Background: Topical corticosteroids (TCs) are widely used for dermatologic diseases. Unfortunately, there exists many adverse effects (local and systemic). These adverse effects are comparable to those observed when glucocorticoids are administered systemically, but they are typically less severe. Aim: ...
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Background: Topical corticosteroids (TCs) are widely used for dermatologic diseases. Unfortunately, there exists many adverse effects (local and systemic). These adverse effects are comparable to those observed when glucocorticoids are administered systemically, but they are typically less severe. Aim: To assess the systemic adverse effects of topical clobetasol (TCL) and counterfeit cosmetic products (CCP) on Iraqi women. Methods and patients: This was a cross-sectional observational study; carried out from October 2022 to March 2023. Patients visited the outpatient clinic of the Department Dermatology and Venereology in Abu-al Khasib Hospital in Basra City, Iraq. Patients may be categorized into two distinct groups: the first group of subjects utilized TCL (n=31), while the second group consisted of patients with CCP (n=32), and the remaining participants were designated as the control group (n=35). A specialized dermatologist conducted a clinical examination to make a diagnosis. A questionnaire was collected, and blood samples were obtained for laboratory investigations. Results: TCs suppressed vitamin D (Vit-D), interlukin-6 (IL-6), testosterone, and estrogen and reduced cortisol concentrations significantly. TCs elevated red blood cells (RBC), neutrophils percent (NEU%), and hemoglobin (HB) levels significantly and prolong bleeding time. While not affecting WBCs, PLT, MPV, MCH, MCV, ACTH, or insulin levels, with decreased in HCT, MCHC, Eos%, and Lym% for all groups in comparison to control group. Conclusion: Topical corticosteroids are extensively used, mostly for the treatment of dermatological conditions. However, they can be misused for their cosmetic effects as fairness creams. TCs misuse is a big problem in Iraq, resulting in massive skin effects and systemic deterioration, such as hematological and hormonal effects. Nevertheless, the general population remains ignorant of the systemic adverse effects. Educational activities targeting the public are suggested to address the systemic deterioration.
Pharmacology and Toxicology
Maha Abdalwahab Mahmood; Shatha Hani Mohammad
Abstract
Background: Cilnidipine, a common hypertension medication, is now being studied for its potential to improve insulin sensitivity, which plays a key role in regulating blood sugar levels. Recent research suggests that cilnidipine may benefit individuals with both hypertension and insulin resistance, offering ...
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Background: Cilnidipine, a common hypertension medication, is now being studied for its potential to improve insulin sensitivity, which plays a key role in regulating blood sugar levels. Recent research suggests that cilnidipine may benefit individuals with both hypertension and insulin resistance, offering a promising avenue for further investigation and potential therapeutic applications. Objective: The present study aimed to investigate the influence of cilnidipine on insulin sensitivity, seeking to comprehend how this medication affects the body's capacity to utilize insulin efficiently. Methods: The current literature search was conducted using diverse databases, primarily including PubMed, Elsevier, Google Scholar, and the Iraqi Virtual Science Library. The search was limited to publications up to [2009-2023], and the keywords "Cilnidipine" and "Insulin Sensitivity" were used to identify relevant articles. Inclusion and exclusion criteria were applied to filter the search results, and the number of papers retrieved meeting these criteria was recorded for further analysis. Results: indicate that cilnidipine may have a positive impact on insulin sensitivity in individuals with hypertension and type 2 diabetes. This suggests that cilnidipine could potentially be a beneficial therapeutic option for addressing insulin resistance in these patients. However, it is crucial to note that further research is necessary to confirm these findings and evaluate the long-term effects of cilnidipine on insulin sensitivity. Conclusion: The results of this study indicate a potential positive impact of cilnidipine on insulin sensitivity in individuals with both hypertension and type 2 diabetes. This suggests that cilnidipine could serve as a promising therapeutic option for addressing insulin resistance in these patients.
Pharmacology and Toxicology
Yaseen Khamees Jumaah; Zainab Haitham Fathi; Jehan Abdulwahab Mohammad
Abstract
Background: Angiotensin-converting enzyme (ACE) Inhibitors are medications pivotal in cardiovascular disease management, impacting the renin-angiotensin system which plays a critical role in cardiovascular health. These inhibitors not only modulate blood pressure and fluid balance but also influence ...
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Background: Angiotensin-converting enzyme (ACE) Inhibitors are medications pivotal in cardiovascular disease management, impacting the renin-angiotensin system which plays a critical role in cardiovascular health. These inhibitors not only modulate blood pressure and fluid balance but also influence adipose-derived hormones like visfatin and apelin. These adipokines are intricately linked with cardiovascular function and interact with the renin-angiotensin system, thereby affecting cardiovascular disease outcomes. Understanding the interplay between ACE inhibitors, visfatin, and apelin is crucial for optimizing therapeutic strategies in cardiovascular disease management. Visfatin is primarily expressed in visceral adipose tissue and is associated with hypertension, vascular inflammation, and insulin resistance. Elevated serum levels of visfatin correlate with increased systolic and diastolic blood pressure. Apelin, acting through the G protein-coupled receptor APJ, is implicated in cardiac system diseases and can lower arterial blood pressure, improving cardiac output. Different apelin isoforms have varying efficacies in arterial pressure regulation. ACE inhibitors, widely prescribed for hypertension and heart failure, are found to modulate serum levels of apelin and visfatin, potentially augmenting their cardioprotective effects. Aim: This review article aims to elucidate the effects of angiotensin-converting enzyme (ACE) inhibitors on the serum levels of visfatin and apelin and their implications for cardiovascular disease management. Conclusion: The interactions between ACE inhibitors, visfatin, and apelin present promising avenues for targeted therapies in hypertension and cardiovascular diseases. Despite some inconsistencies in the research, understanding these interactions could lead to novel therapeutic approaches and enhanced cardiovascular care.
Pharmacology and Toxicology
Zahraa Alhalawachee; Ghada Abd Alrhman Abd Alrhman Taqa
Abstract
Background: One of the most common chronic diseases globally is hypothyroidism. Thyroid hormones serve a significant role in maintaining the proper function and shape of the salivary gland. The aim of the study: Investigate the function of Ashwagandha roots extract in providing a protection role for ...
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Background: One of the most common chronic diseases globally is hypothyroidism. Thyroid hormones serve a significant role in maintaining the proper function and shape of the salivary gland. The aim of the study: Investigate the function of Ashwagandha roots extract in providing a protection role for salivary glands in hypothyroid rats following postnatal exposure to Propylthiouracil. Materials and Methods: Ten pregnant albino rats were obtained. Until the rat pups were detected, each pregnant rat was kept individually in clean rodent plastic. At postnatal day 3 (PND3), forty male rats were randomly assigned to one of two groups: group A, which served as a control group, and group B, which received orally (1mg/kg) Propylthiouracil (PTU) for three weeks. At PND22, group B was divided up into three subgroups: B1, the hypothyroid group that got no therapy; B2, the hypothyroid group that received an aqueous extract of Ashwagandha roots (200 mg/kg) for 21 days; and B3, the hypothyroid group that received Levothyroxine (4g/100g/day) for 21 days. At the end of the trial, the submandibular gland was assessed using sonographic instruments in all groups. Results: the sonographic assessment of hypothyroid group’s submandibular gland showed an increase in the overall size of the gland, a heterogeneous gland with a honeycomb appearance and hypoechoic regions in group remains without treatment, while the results in hypothyroid pups fed with Ashwagandha roots extract indicated a small improvement in gland size and echotexture when compared to pups who received levothyroxine, owing to its antioxidant properties.
Pharmacology and Toxicology
Muthanna Taha Khalaf; Ahmed Shuaib Karmoosh; Akram Ahmed Hamo; Zinah Jasim Mohammed
Abstract
Background: When the thyroid gland becomes overactive or underactive, a variety of health issues may occur, including eye illnesses. Thyroxine (T4) and triiodothyronine (T3) are the two primary hormones produced by the thyroid gland. These hormones are essential for maintaining of proper eye function. ...
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Background: When the thyroid gland becomes overactive or underactive, a variety of health issues may occur, including eye illnesses. Thyroxine (T4) and triiodothyronine (T3) are the two primary hormones produced by the thyroid gland. These hormones are essential for maintaining of proper eye function. When the thyroid gland is hyperactive, it can cause a variety of eye disorders for example Graves' ophthalmopathy. Aim: To explore the potential link between eye disorders and toxic thyroid glands, specifically how hyperthyroidism (an overactive thyroid gland) may contribute to the development of eye conditions like Graves' ophthalmopathy. . The ultimate goal is to enhance patient outcomes through better knowledge and management of these complicated illnesses. Patients and Methods: The second survey questionnaire was completed by 100 patients with thyroid disorders. Several approaches are available to assess the link between ocular problems and toxic thyroid glands. Among these methods are Thyroid Function Tests and a Comprehensive Eye Exam: Thyroid function tests include measuring the plasma levels of TSH, T3, and T4 levels to see if there is an underlying thyroid gland dysfunction which may produce abnormalities in the eyes. Results: The study included 100 patients, with 81% of them being women. Individual ocular problems are more common in male than in female patients. Exophthalmos was reported by about 70% of the men (the most frequently). Patients also frequently reported redness of the eyes (68%), edema or swelling of the eyelids (67%), and ocular dryness (61%). They were less likely to have a hazy vision, but about one-third did. Conclusion: Hyperthyroidism and Graves' disease can lead to eye problems such as bulging eyes, double vision, dry eyes, and sensitivity to light. It is important to have regular eye exams and seek medical attention if any changes occur.
Pharmacology and Toxicology
Ghada M Ahmed; Mohammed N Abed; Fawaz A Alassaf
Abstract
Background: Sodium-Glucose Co-Transporter-2 Inhibitors (SGLT2-IS) have been shown to increase hemoglobin (Hb) levels, hematocrit, and erythrocyte count. It has also been found that these agents can potentially reduce the risk of anemia and minimize the need for erythropoiesis stimulating agents (ESA) ...
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Background: Sodium-Glucose Co-Transporter-2 Inhibitors (SGLT2-IS) have been shown to increase hemoglobin (Hb) levels, hematocrit, and erythrocyte count. It has also been found that these agents can potentially reduce the risk of anemia and minimize the need for erythropoiesis stimulating agents (ESA) and other treatments in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). However the precise mechanism for such an effect is still conflicting. Aim: We aimed at providing an overview of the effects of SGLT2-IS on hematological parameters, specifically focusing on their potential to improve anemia and erythropoiesis in patients with diabetes mellitus (DM). Additionally the proposed mechanisms by which SGLT2-IS may improve Hb levels besides their clinical importance and future directions will also be highlighted. Results: Based on the obtained data from latest literatures, SGLT2-IS may improve the status of anemia and other linked abnormalities via their mild diuretic potential, effects on erythropoietin (EPO) production, and possible increase in renal oxygen delivery. Conclusion: SGLT2-IS may have a promising role in improving multiple aspects of blood, circulatory and renal systems health in patients with DM, beyond their primary glucose-lowering role.