Design and Synthesis of 1,2,3-triazole-Acetaminophen Hybrids from Expired Commercial Acetaminophen Tablets and their In-silico ADME-Tox Properties | Chapter 8 | Current Innovations in Chemical and Materials Sciences Vol. 9

 

A combination of two promising pharmacophore cores like 1,2,3-triazole (TA) and acetaminophen (APAP) in a single molecular entity could be useful in the lead optimization step of drug research. Therefore, designing and preparing new conjugated TA-APAP molecules is an important and actual task. This book chapter describes an impressively efficient catalyzed Huisgen reaction-based method for preparing a series of new 1-substituted 1,2,3-triazole-acetaminophen hybrids. The developed method, which does not require chromatography column separation, is a practical and efficient solution. It consists of the initial efficient O-propargylation reaction of APAP and subsequent CuBr(PPh3)3-catalyzed [3+2] cycloaddition reaction between O-propargylated APAP and diverse organoazides (R-N3) in the presence of tert-BuOH: H2O (1:1) system. APAP was easily obtained from expired commercial tablets using solid-liquid extraction as a starting material. An interesting nitric oxide-releasing 1,2,3-triazole hybrid of APAP was also obtained straightforwardly employing the developed method. These new drug hybrids were obtained with good yields (64–93%). According to the in-silico ADME-Tox assessment studies performed in this work and literature analysis, these hybrids could be interesting models in search of new pharmacological nontoxic agents endowed with anti-inflammatory and anticancer properties.

Author(s) Details:

Daniela Calderón Lamus,
Laboratorio de Química Orgánica y Biomolecular, Escuela de Química, Universidad Industrial de Santander, A.A. 680002, Bucaramanga, Colombia.

Prof. Dr. Vladimir V. Kouznetsov
Laboratorio de Química Orgánica y Biomolecular, Escuela de Química, Universidad Industrial de Santander, A.A. 680002, Bucaramanga, Colombia.

 

Please see the link here: https://stm.bookpi.org/CICMS-V9/article/view/14339

Assessment of Risks for Renal Dysfunction: An Approach towards Light to Moderate Drinking and Therapeutic Doses of Acetaminophen | Chapter 20 | Current Practice in Medical Science Vol. 1

This study examined the kidney's response to therapeutic doses of acetaminophen (APAP) and light-to-moderate alcohol use while controlling for conditions including hypertension, diabetes, and obesity that might increase the kidney's susceptibility to APAP and/or alcohol toxicity. The study was a secondary data analysis of the 2003–2004 National Health and Nutrition Examination Survey (NHANES). Odds ratios (OR) and 95 percent confidence intervals (CI) were generated from multiple logistic regression models by further controlling for potential predisposing factors like namel to compare the likelihood that people who ingested therapeutic doses of APAP and light–moderate amounts of alcohol, compared to those who did not, would have kidney dysfunction. Even after controlling for hypertension, diabetes, and obesity, respondents who reported using therapeutic doses of APAP and light-to-moderate amounts of alcohol had statistically significant higher odds of developing renal dysfunction [OR(95 percent CI) = 1.64(1.28-2.10) self-report, 2.18(1.81-2.63) SCr, 4.60(3.03-7.00) BUN, 3.14(2.42-4.07) GFR, and 1.71(1.36-2.14) ALBCR]. On the kidney, APAP and alcohol were thought to have harmful effects. Unknown threshold dosages exist at which these effects start to manifest. The results of this study indicate that even therapeutic dosages of APAP and light to moderate amounts of alcohol may have negative health effects when drunk together. Given that many individuals may be exposed to both APAP and alcohol, this study brings to light a crucial public health issue. The findings could have an impact on health policy. We also investigated the possible effects of conditions that may make the kidney more vulnerable to APAP and/or alcohol toxicity, such as hypertension, diabetes, and obesity.

Author(s) Details:

Harrison Ndetan,

Department of Epidemiology and Biostatistics, School of Community and Rural Health, University of Texas Health Science Center, 11937 US Hwy 271, Tyler, TX 75708, United States of America.

Marion W. Evans Jr,

Department of Food Science, Nutrition, and Health Promotion, 105 Herzer Building, Box 9805, Mississippi State, MS 39762, United States of America.

Ashwani K. Singal,

Division of Gastroenterology and Hepatology, Department of Medicine, University of Alabama Birmingham, 1720 2nd Ave, South, BDB 380, Birmingham, AL 35294-0012, United States of America.

Lane J. Brunner,

Ben and Maytee Fisch College of Pharmacy, University of Texas, Tyler, 3900 University Blvd, Tyler, TX 75799, United States of America.

Kirk Calhoun,

University of Texas Health Science Center, 11937 US Hwy 271, Tyler, TX 75708, United States of America.

Karan P. Singh,

Department of Epidemiology and Biostatistics, School of Community and Rural Health, University of Texas Health Science Center, 11937 US Hwy 271, Tyler, TX 75708, United States of America.

George Einstein,

University of Science, Arts and Technology (USAT), Olveston, Montserrat.

Orien Tulp,

University of Science, Arts and Technology (USAT), Olveston, Montserrat.

Please see the link here: https://stm.bookpi.org/CPMS-V1/article/view/7339

Phytochemical Appraisal and Evaluation of Effects of Aqueous Extract of Hypoestes rosea on Haematological Parameters of Acetaminophen – Induced Toxicity in Albino Rats| Chapter 10 | New Visions in Biological Science Vol.10

 Hypoestes rosea leaves are used as traditional medicine in most of Nigeria's Niger Delta regions and the western portion of Cameroon to treat a variety of diseases and sick states in children, such as fever, anaemia, and malaria. Despite its widespread use, research on its phytochemicals and effects on haematological parameters is limited. As a result, this study analyses its phytochemical evaluation and assesses the effects of an aqueous extract of Hypoestes rosea on haematological parameters in albino rats exposed to acetaminophen-induced toxicity. The goal of this study is to determine the phytochemical composition and haematological consequences of oral administration of crude extract leaves of Hypoestes rosea in albino rats. Acetaminophen, a regularly used painkiller and antipyretic, can be harmful and detrimental to essential organs of the body, disrupting homeostasis and erythropoiesis at high doses. In this study, phytochemical analysis of Hypoestes rosea leaves revealed the presence of flavonoids, tannins, alkaloids, terpenoids/steroids, saponins, carbohydrates, and cardiac glycosides, whereas the effects of an aqueous extract of Hypoestes rosea (AEHr) on haematological parameters of acetaminophen-induced toxicity in albino rats were assessed using acute (15 days) and sub-chronic (30 days) study durations A total of 156 adult albino rats weighing 180-220g were utilised in this investigation, 44 for the toxicity study and 112 for the extract control (EC), negative control (NC), positive control (PC), AEHr100mg/kg b w., AEHr 200mg/kg b w., and AEHr 300mg/kg b w. groups, each with six rats. After chloroform anaesthesia in a desiccator at the end of the study period, blood samples for haematological parameters were taken through jugular puncture (PCV, HB, RBC, WBC & Platelets). The results demonstrated that acetaminophen induction produced anaemia in albino rats, as evidenced by significant reductions in PCV, HB, RBC, and WBC levels. When comparing the PC group to the other experimental groups, P0.05 was found. However, different concentrations of aqueous extract of Hypoestes rosea were able to restore anaemia caused by acetaminophen induction to normal in a dose-dependent manner during different treatment stages in the acute and sub-chronic period. As a result, the findings of this study imply that Hypoestes rosea contains active components and phytochemicals that are responsible for its erythropoietic characteristics in rats, and that it should be studied further in higher mammals.

 

Author(s) Details:

E. Ogregade Ileimokumo,
Rivers State University / Bayelsa Medical University, Nigeria.


S. Bartimaeus Ebirien-Agana,
Rivers State University, Nigeria.


Igwe Felix,
Rivers State University, Nigeria.

G. Davies Tamuno-Emine,
Rivers State University, Nigeria.

Please see the link here: https://stm.bookpi.org/NVBS-V10/article/view/5989

NRCT Clinical Study in to Identify Acetaminophen-Induced Liver Injury Mechanism | Chapter 5 | Issues and Development in Health Research Vol. 3

 Acetaminophen (APAP) (N-acetyl-p-aminophenol) is a chemical compound utilised in paracetamol treatments to reduce pain and lower fever. In June 2009, an FDA advisory group issued a warning concerning the potential of APAP overdose due to the drug's side effects, which include drug-induced liver damage. In addition, the FDA has begun collecting data on APAP toxicity biomarkers in children and adolescents through multicenter non-interventional case-control studies. The National Center for Toxicological Research is a non-profit organisation that does toxicological research (NCTR), In partnership with various health institutes (hospitals, universities, and clinical centres) around the United States, the FDA coordinates the execution of APAP clinical trials. The purpose of these clinical trials is to collect enough data to build a list of biomarkers linked to acetaminophen toxicity that can be matched with specific adduct proteins; this information can then be used to investigate and predict future risks in children who are taking acetaminophen.

Author (S) Details

Yawo Akrodou
Department of Health Science, Walden University, Minneapolis, USA.

View Book :- https://stm.bookpi.org/IDHR-V3/article/view/3299

Tomato (Lycopersicon esculentum) Extracts Elicit Anti-Hepatotoxic Effects on Acetaminophen-Induced Liver Injury in Albino Wistar Rat | Chapter 4 | Technological Innovation in Pharmaceutical Research Vol. 10

 Introduction: Drug overdose is the largest cause of liver injury in the world today, according to numerous reports. Natural antioxidant-rich diets have been shown to provide significant relief from drug-induced organ damage.

The goal of this investigation was to see if tomato extract could protect rats from acetaminophen-induced acute hepatotoxicity.

Methods: Phytochemical tests were carried out. A total of 24 albino rats weighing 11010 g were divided into four groups (A-D), each with six rats. The usual control group, Group A, received no treatment. The negative control group got only a single dose of acetaminophen (750 mg/kg, i.p) as a single dose. The test group got a single dose of acetaminophen (750 mg/kg, i.p.) before receiving 14 days of therapy with tomato extract (30 mg/kg, oral). For 14 days, Group D was given tomato extract (30 mg/kg, oral) and acetaminophen (750 mg/kg, i.p) at the same time.

When compared to normal (p0.05 or p0.01), a single dosage of Acetaminophen induced liver cell damage and a significant increase in the levels of the liver enzymes: AST (67.6711.41U/L); ALT (46.3310.59U/L); and ALP (223.7023.31U/L) in rats in negative control. On the liver enzyme marker levels, daily injection of tomato extract was able to reduce the acetaminophen-induced hepatotoxicity: AST (23.00 3.61U/L, P0.01), ALT (17.67 3.48U/L, P0.05), and ALP (121.308.11U/L, P0.01) were all higher in Group C. When compared to the negative control group, AST (26.672.91U/L, P0.01), ALT (18.671.76 U/L, P0.05), and ALP (124.729.33U/L, P0.01) were significantly higher in Group D. In comparison to the normal control group, histological data demonstrated no substantial liver injury in the tomato extract groups.

Tomato extract has hepatoprotective properties against acetaminophen-induced liver damage.

Author (S) Details

I. K. Uchendu
Department of Medical Laboratory Science, Division of Clinical Chemistry, University of Nigeria, Enugu Campus, Enugu State, Nigeria.

C. E. Agu
Department of Medical Laboratory Science, Division of Clinical Chemistry, University of Calabar, Nigeria.

O. C. Orji
Department of Medical Laboratory Science, Division of Clinical Chemistry, University of Nigeria, Enugu Campus, Enugu State, Nigeria.

E. B. Nnedu
Department of Medical Laboratory Science, Division of Immunology, University of Nigeria, Enugu Campus, Nigeria.

C. Arinze
Department of Medical Laboratory Science, Division of Clinical Chemistry, University of Nigeria, Enugu Campus, Enugu State, Nigeria.

A. C. Uchenna
Department of Medical Laboratory Science, Division of Medical Microbiology, University of Nigeria, Enugu Campus, Enugu State, Nigeria.

U. C. Okongwu
Department of Medical Laboratory Science, Division of Medical Microbiology, University of Nigeria, Enugu Campus, Enugu State, Nigeria.

View Book :- https://stm.bookpi.org/TIPR-V10/article/view/2841

Study on the effect of Aqueous Extract of Bitter Leaf (Vernonia amygdalina) Against Acetaminophen-Induced Liver Damage in Rats | Chapter 3 | Technological Innovation in Pharmaceutical Research Vol. 10

 The goal of this investigation was to see if Vernonia amygdalina aqueous extract could protect abino wistar rats against acetaminophen-induced liver injury.

Methods: Twenty-five (25) albino rats weighing 120–20 g were allocated into five (5) groups, each with five (5) rats. Group A was used as a control group and did not receive any treatment. As a negative control, Group B received only a single dosage of acetaminophen (750 mg/kg, i.p.). Following an acetaminophen challenge, Group C got Vitamin C (200 mg/kg, oral) for 2 weeks, whereas Group D and E received aqueous bitter leaf extract; high dose (500 mg/kg, oral) and low dose (250 mg/kg, oral) separately for 2 weeks.

Results: A single dose of acetaminophen (750 mg/kg, i.p.) caused liver damage, with AST, ALT, and ALP values of 48.3310.14, 60.0013.23, and 229.6723.38U/L, respectively. When compared to acetaminophen alone, bitter leaf treatment reversed acetaminophen-induced liver damage, with AST, ALT, and ALP levels of 20.671.76U/L (P0.05), 16.673.52U/L (P0.01), and 131.677.27U/L (P0.01), respectively. The test groups likewise had mild or non-significant hepatic damage, indicating that Vernonia amygdalina provides hepatoprotection.

Conclusion: Vernonia amygdalina aqueous extract has hepatoprotective effects against acetaminophen-induced liver injury.

Author (S) Details

I. K. Uchendu
Department of Medical Laboratory Science, Division of Clinical Chemistry, University of Nigeria, Enugu Campus, Enugu State, Nigeria.

View Book :- https://stm.bookpi.org/TIPR-V10/article/view/2840

Approach to Early Detection and Management of Kidney Disease | Chapter 8 | Technological Innovation in Pharmaceutical Research Vol. 6

 The effectiveness of glomerular filtration is measured by serum urea (sU), which is generated in the liver, and serum creatinine (sCr), which is a breakdown product of muscle cells. Both sU and sCr have low predictive accuracy for renal injury, especially in the early stages of kidney disease, because they are evaluated when 60-70 percent of nephrons have already been damaged and kidney diseases have progressed to the point where dialysis or kidney transplantation are the only options. As a result, individuals face a variety of health issues as they approach death. As a result, early diagnosis of kidney injury using direct kidney injury markers, renal tubule injury markers, and proteomic genomic markers of kidney disorders from both urine and serum, as well as alternative treatment strategies for kidney disease management using medicinal plants, is now more important than ever. Tubular damage markers, such as KIM-1, proteomic and genomic markers from the proximal nephron, kidney functional markers, such as cystatin C, and oxidative stress markers, such as Malon di aldehyde (MDA), alpha Glutathione S Transferase (alpha GST). When renal tubules are stressed and wounded, key mediators such as IL-18, KIM-1, cystatin C, and GST emerge in urine. Terminellia arjuna (TA), a medicinal plant used in Ayurvedic medicine, includes phytoconstituents such as triterpenoids, tannins, flavonoids, and others that have been shown to have anti-cardiovascular, anti-cancer, anti-microbial, and nephroprotective characteristics. Antiuremic effects of aqueous bark extract of TA have been demonstrated in our laboratory on dehydration-induced uremic rats. As a result, the publication was written to look into kidney damage proteome and genomic biomarkers from both serum and urine in acetaminophen-induced renal problem rats, as well as to look into the therapeutic efficiency of phytocompounds from Terminalia arjuna bark (TA).

The first was to identify the best biomarkers for early screening of kidney disorders, whether they were plasma urea and creatinine or novel urinary low molecular weight protein biomarkers such as Interlukin-18 (IL-18), Kidney injury molecule-1 (KIM-1), and cystatin –C. Second, the therapeutic efficacy of Terminalia arjuna (MFTA) methanol fraction on urine new biomarkers.

Results demonstrated that APAP administration for 5 days, 10 days, and 15 days elevated novel urinary biomarkers such as IL-18, KIM-1, and cystatin-C by nearly twofolds and cystatin-C by nearly sixfolds compared to old biomarkers plasma urea and plasma creatinine. The protective impact of APAP with co-administration of MFTA was demonstrated by a decrease in established and new unique biomarkers such as Superoxide dismutase (SOD) and catalase, whereas the amount of malondialdehyde (MDA) increased. In APAP treatment rats, SDS-PAGE revealed new low molecular weight urine protein bands, whereas in normal rats, there was no band at this molecular level.

Conclusion: MFTA is the most potent nephroprotective drug, and urine low molecular proteins, rather than plasma urea and creatinine, are the best diagnostic tools for early diagnosis of kidney disease.

Author (s) Details

Deblina Giri
Research Unit, Department of Nutrition, Raja Narendralal Khan Women’s College, Midnapore-721102, Dist- Paschim Medinipur, West Bengal, India.

Dr. Koushik Das
Research Unit, Department of Nutrition, Belda College, Belda-721424, Dist- Paschim Medinipur, West Bengal, India.

Dilip Kumar Nandi
Department of Post Graduate Physiology of Raja Narendralal Khan Women’s College, Midnapore-721102, Dist- Paschim Medinipur, West Bengal, India.

View Book :- https://stm.bookpi.org/TIPR-V6/article/view/1708

A Narrative Review on the Effect of Acetaminophen and Ibuprofen in Orthodontic Tooth Movement | Chapter 14 | Challenges in Disease and Health Research Vol. 4

 Application of orthodontic force causes an inflammatory event resulting in bone resorption and subsequent orthodontic tooth movement (OTM) in the periodontium. The release of inflammatory mediators such as E2 prostaglandins and Interleukin-1β serve as potent bone resorption stimulators. Strong force application results in discomfort and the same non-steroidal anti-inflammatory medications (NSAIDs) are recommended for relief. By interfering with prostaglandin (PG) synthesis, these NSAIDs negate the inflammatory reactions, thereby inhibiting orthodontic tooth movement. The aim of this mini literature review was to highlight the impact on their pain relieving capacity and effect on OTM of the two widely used medications, namely acetaminophen and ibuprofen. It was concluded that acetaminophen was a potent analgesic that could be used to alleviate orthodontic treatment-related pain because its effect was at the level of the central nervous system and not at the cell level. The degree of the membrane as well as its inhibitory effect on OTM was not a matter of concern as it inhibited the PG synthesis only slightly. Ibuprofen, on the other hand, acted as a mild analgesic and, with its anti-inflammatory effect, also inhibited OTM. At the peripheral stage, ibuprofen reduces PGs, thereby influencing osteoclastic activity and the subsequent deceleration of orthodontic tooth movement. Instead of ibuprofen, acetaminophen is the recommended medication of choice for reliving pain and discomfort during orthodontic therapy.

Author (s) Details

Dr. A. Arif Yezdani
Department of Orthodontics and Dentofacial Orthopedics, Sree Balaji Dental College and Hospital, Bharath Institute of Higher Education and Research, Chennai, Tamil Nadu, India.


Dr. Mansi Giri
Department of Orthodontics and Dentofacial Orthopedics, Sree Balaji Dental College and Hospital, Bharath Institute of Higher Education and Research, Chennai, Tamil Nadu, India.

View Book :- https://bp.bookpi.org/index.php/bpi/catalog/book/287