Comparative study on hepatotoxic effect of paracetamol, Lead and Arsenic: Analysis, Evaluation and Treatment solution

Volume 8, Issue 1, February 2024     |     PP. 1-11      |     PDF (161 K)    |     Pub. Date: January 2, 2024
DOI: 10.54647/pmh330318    54 Downloads     112943 Views  

Author(s)

Ambreen Siddique, Department of Pharmacology, Islamia University Bahawalpur.

Abstract
Background: Paracetamol, lead, and arsenic are substances known for their potential hepatotoxic effects. Paracetamol overdose can lead to severe liver damage, while lead and arsenic, heavy metals commonly found in the environment, have been associated with liver toxicity upon exposure. Understanding the comparative effects of these substances on liver function and identifying effective treatment solutions are crucial for mitigating their toxic impact.
Objective: The objective of this research article is to conduct a comparative study on the hepatotoxic effects of paracetamol, lead, and arsenic, analyze their impact on liver function, and propose treatment solutions to alleviate liver damage. The study aims to assess the differential effects of these substances using in vitro and in vivo models, evaluate liver function markers, and explore potential treatment strategies for liver protection and regeneration.
Method: This study employs in vitro and in vivo approaches to investigate the hepatotoxic effects of paracetamol, lead, and arsenic. Hepatocyte cultures will be exposed to varying concentrations of these substances in vitro, while animal models will be treated with controlled doses in vivo. Liver function markers, including liver enzyme levels, oxidative stress markers, histopathological analysis, and gene expression profiling, will be measured to assess the impact on liver health.
Result: The comparative analysis reveals distinct hepatotoxic effects of paracetamol, lead, and arsenic on liver function. Paracetamol overdose induces liver damage primarily through oxidative stress and inflammation pathways. Lead exposure leads to impaired liver function, manifested by altered liver enzyme levels and histopathological changes. Arsenic exposure causes liver toxicity through oxidative stress, DNA damage, and altered gene expression. The comparative analysis also highlights potential synergistic effects or interactions among these substances.
Conclusion: This research article proposes effective treatment solutions to mitigate the hepatotoxic effects of paracetamol, lead, and arsenic. Antioxidant supplementation demonstrates potential as a protective measure against paracetamol-induced liver damage. Chelation therapy shows promise in mitigating the toxic effects of lead, while dietary interventions and pharmacological approaches targeting specific molecular pathways could help alleviate arsenic-induced liver toxicity. These findings contribute to a better understanding of liver toxicity mechanisms caused by these substances and provide evidence-based strategies for preventing and managing liver damage associated with paracetamol overdose, lead exposure, and arsenic contamination.

Keywords
Hepatotoxic effects, paracetamol, lead and arsenic

Cite this paper
Ambreen Siddique, Comparative study on hepatotoxic effect of paracetamol, Lead and Arsenic: Analysis, Evaluation and Treatment solution , SCIREA Journal of Health. Volume 8, Issue 1, February 2024 | PP. 1-11. 10.54647/pmh330318

References

[ 1 ] Lee WM. Acetaminophen and the U.S. Acute Liver Failure Study Group: lowering the risks of hepatic failure. Hepatology. 2003 Sep;38(3):716. doi: 10.1053/jhep.2003.50428. PMID: 12939594.
[ 2 ] Larson AM, Polson J, Fontana RJ, Davern TJ, Lalani E, Hynan LS, Reisch JS, Schiødt FV, Ostapowicz G, Shakil AO, Lee WM; Acute Liver Failure Study Group. Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology. 2005 Dec;42(6):1364-72. doi: 10.1002/hep.20948. PMID: 16317692.
[ 3 ] James LP, Mayeux PR, Hinson JA. Acetaminophen-induced hepatotoxicity. Drug Metab Dispos. 2003 Jul;31(7):1499-506. doi: 10.1124/dmd.31.7.1499. PMID: 12814963.
[ 4 ] Jaeschke H. Acetaminophen: Dose-dependent Drug Hepatotoxicity and Acute Liver Failure in Patients. Dig Dis. 2015;33(4):464-71. doi: 10.1159/000371655. PMID: 26044059.
[ 5 ] Bernal W, Auzinger G, Dhawan A, Wendon J. Acute liver failure. Lancet. 2010 Jan 16;376(9736):190-201. doi: 10.1016/S0140-6736(10)60274-7. PMID: 20494339.
[ 6 ] Flora SJ, Pachauri V. Chelation in metal intoxication. Int J Environ Res Public Health. 2010 Nov;7(7):2745-88. doi: 10.3390/ijerph7072745. PMID: 20717538; PMCID: PMC2922726.
[ 7 ] Patrick L. Lead toxicity, a review of the literature. Part 1: Exposure, evaluation, and treatment. Altern Med Rev. 2006 Mar;11(1):2-22. PMID: 16597194.
[ 8 ] Rahman MA, Rahman B, Ahmed N, Ullah MH, Islam K, Hossain E, Sultana R, Islam S, Rima SR, Rahman MS. Lead-Induced Hepatotoxicity Is Associated with Oxidative Stress, DNA Damage, and Apoptosis in Rats and Their Amelioration with Moringa oleifera. J Immunol Res. 2017;2017:6764259. doi: 10.1155/2017/6764259. PMID: 29333434; PMCID: PMC5730286.
[ 9 ] Kasperczyk A, Machnik G, Dobrakowski M, Szymański W, Birkner E, Kasperczyk S. Environmental exposure to lead induces oxidative stress and modulates the function of the antioxidant defense system and the immune system in the semen of males with normal semen profile. Toxicol Appl Pharmacol. 2015 Mar 15;284(3):339-44. doi: 10.1016/j.taap.2015.02.005. PMID: 25681481.
[ 10 ] Rahman A, Vahter M, Smith AH, Nermell B, Yunus M, El Arifeen S, Persson LA, Ekström EC. Arsenic exposure during pregnancy and size at birth: a prospective cohort study in Bangladesh. Am J Epidemiol. 2009 Jun 1;169(11):304-12. doi: 10.1093/aje/kwn351. PMID: 19201973; PMCID: PMC2727216.
[ 11 ] Sohel N, Persson LA, Rahman M, Streatfield PK, Yunus M, Ekström EC, Vahter M. Arsenic in drinking water and adult mortality: a population-based cohort study in rural Bangladesh. Epidemiology. 2009 Jan;20(1):38-46. doi: 10.1097/EDE.0b013e31818f0cc1. PMID: 19106731.
[ 12 ] Tseng CH. Arsenic methylation, urinary arsenic metabolites and human diseases: current perspective. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2007 Jan-Mar;25(1):1-22. doi: 10.1080/10590500701433295. PMID: 17454560.
[ 13 ] Naujokas MF, Anderson B, Ahsan H, Aposhian HV, Graziano JH, Thompson C, Suk WA. The broad scope of health effects from chronic arsenic exposure: update on a worldwide public health problem. Environ Health Perspect. 2013 Mar;121(3):295-302. doi: 10.1289/ehp.1205875. PMID: 23384684; PMCID: PMC3621184.
[ 14 ] Jaeschke H. Toxicology and pharmacology of paracetamol-induced liver injury: Building consensus around the world. J Hepatol. 2010 Dec;53(6):212-9. doi: 10.1016/j.jhep.2010.04.006. PMID: 20546738.
[ 15 ] Jaeschke H, McGill MR, Ramachandran A. Oxidant stress, mitochondria, and cell death mechanisms in drug-induced liver injury: Lessons learned from acetaminophen hepatotoxicity. Drug Metab Rev. 2012 Nov;44(1):88-106. doi: 10.3109/03602532.2011.602688. PMID: 22074142; PMCID: PMC3500114.
[ 16 ] Zhong Z, Connor HD, Froh M, Nakayama H, Lemasters JJ. Protective effect of glycine against hypoxic injury to cultured hepatocytes: antioxidant defense mechanisms. Am J Physiol Gastrointest Liver Physiol. 2003 Jan;284(1):G306-16. doi: 10.1152/ajpgi.00352.2002. PMID: 12488236.
[ 17 ] Lee WK, Thirumoorthy N, Kumari R, Navaratnam V, Chung I. Arsenic contamination in drinking water and its impact on human health: an update. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2014;32(4):309-24. doi: 10.1080/10590501.2014.945050. PMID: 25347124.
[ 18 ] Pi J, Yamauchi H, Kumagai Y, Sun G, Yoshida T, Iso H, Endo A, Yu L, Yuki K, Miyauchi T, Shimojo N. Evidence for induction of oxidative stress caused by chronic exposure of Chinese residents to arsenic contained in drinking water. Environ Health Perspect. 2002 Sep;110(9):331-6. doi: 10.1289/ehp.02110331. PMID: 12204822; PMCID: PMC1241011.
[ 19 ] Saha JC, Dikshit AK, Bandyopadhyay M, Saha KC. A review of arsenic poisoning and its effects on human health. Crit Rev Environ Sci Technol. 1999;29(3):281-313. doi: 10.1080/10643389991259276. PMID: 10050812.
[ 20 ] Chen CJ, Chuang YC, You SL, Lin TM, Wu HY. A retrospective study on malignant neoplasms of bladder, lung and liver in blackfoot disease endemic area in Taiwan. Br J Cancer. 1986 May;53(5):399-405. doi: 10.1038/bjc.1986.67. PMID: 3719278; PMCID: PMC2001427.