ANTIFIBROTIC EFFECTS OF ANGIOTENSIN RECEPTOR BLOCKERS IN ORGANOPHOSPHATE (CHLORPYRIFOS) INDUCED LIVER FIBROSIS
Main Article Content
Keywords
Liver fibrosis, chlorpyrifos, angiotensin receptor blockers, collagen, alpha smooth muscle actin
Abstract
Background: Organophosphates (OPs) are one of the pesticides causing toxicity to humans and animals. OPs toxicity involve many organs such as liver, kidney, nervous system and immune system. Liver fibrosis is a wound healing response in which there is increased production and deposition of extracellular matrix (ECM), due to prolonged injury to liver by viral hepatitis, alcohol consumption, metabolic diseases and toxins (pesticides). Angiotensin receptor blockers (ARBs) are potential therapeutic agents for liver fibrosis.
Objectives: To determine the effects of ARBs on Chlorpyrifos(CPF) induced liver fibrosis.
Methods: 40 adult male albino wistar rats were used in the study. Rats were grouped as control group (A1), positive control group (A2) and experimental groups (B, C and D). Group A2 was treated with carbon tetrachloride (CCL4) to induce liver fibrosis, with 2 ml/kg of 50% solution of CCL4 by oral gavage two times per week for eight weeks, group B was treated with 1ml/bw/day CPF intraperitoneally for eight weeks. Group C was treated with 1ml/bw/day CPF intraperitoneally for eight weeks and then ARBs orally (30mg/kg/day) for 8 weeks. Group D was simultaneously treated with CPF and ARBs for 8 weeks with same doses as for group C. At the end of experiment blood was collected by cardiac puncture for liver function test and rats were sacrificed to collect liver samples. Pathological changes in liver were examined using H&E and Masson’s trichrome staining. Real time PCR was used to detect alpha smooth muscle actin (α-SMA), transforming growth factor beta 1(TGF- β1) and Collagen-I(coll-I) mRNA expression.
Results: CPF caused liver injury evidenced by raised liver enzymes and bilirubin with histological changes and increased expression of genes. ARBs decreases liver enzymes, CPF induced histological changes and decreases the expression of α-SMA, TGF- β1 and Coll-I.
Conclusion: The present study suggests that ARBs prevent fibrogenesis and may serve as a promising therapeutic agent to reduce CPF induced liver fibrosis.
References
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8. Zhao W, Wang X, Sun K-H, Zhou L. α-smooth muscle actin is not a marker of fibrogenic cell activity in skeletal muscle fibrosis. PloS one. 2018;13(1):e0191031.
9. Rockey DC, Du Q, Shi Z. Smooth muscle α-actin deficiency leads to decreased liver fibrosis via impaired cytoskeletal signaling in hepatic stellate cells. The American journal of pathology. 2019;189(11):2209-20.
10. Jallow MF, Awadh DG, Albaho MS, Devi VY, Thomas BM. Pesticide knowledge and safety practices among farm workers in Kuwait: results of a survey. International journal of environmental research and public health. 2017;14(4):340.
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12. Mbah Ntepe LJ, Habib R, Judith Laure N, Raza S, Nepovimova E, Kuca K, et al. Oxidative Stress and Analysis of Selected SNPs of ACHE (rs 2571598), BCHE (rs 3495), CAT (rs 7943316), SIRT1 (rs 10823108), GSTP1 (rs 1695), and Gene GSTM1, GSTT1 in Chronic Organophosphates Exposed Groups from Cameroon and Pakistan. International journal of molecular sciences. 2020;21(17):6432.
13. Karami-Mohajeri S, Ahmadipour A, Rahimi H-R, Abdollahi M. Adverse effects of organophosphorus pesticides on the liver: a brief summary of four decades of research. Arhiv za higijenu rada i toksikologiju. 2017;68(4):261-75.
14. Yassin MM, Al-Najjar MS. Hepatic and Renal Toxicity of Methamidophos in Male Domestic Rabbits: Physiological Aspect. Recent Adv Biol Med. 2020;6(1):12457.
15. Mikhail T, Aggour N, Awadallah R, Boulos M, El-Dessoukey E, Karima A. Acute toxicity of organophosphorus and organochlorine insecticides in laboratory animals. Zeitschrift für Ernährungswissenschaft. 1979;18(4):258-68.
16. Shim KY, Eom YW, Kim MY, Kang SH, Baik SK. Role of the renin-angiotensin system in hepatic fibrosis and portal hypertension. The Korean Journal of Internal Medicine. 2018;33(3):453.
17. Wu C-H, Mohammadmoradi S, Chen JZ, Sawada H, Daugherty A, Lu HS. Renin-angiotensin system and cardiovascular functions. Arteriosclerosis, thrombosis, and vascular biology. 2018;38(7):e108-e16.
18. Bataller R, Schwabe RF, Choi YH, Yang L, Paik YH, Lindquist J, et al. NADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is critical in hepatic fibrosis. The Journal of clinical investigation. 2003;112(9):1383-94.
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21. Liu H, Zhang Z, Hu H, Zhang C, Niu M, Li R, et al. Protective effects of Liuweiwuling tablets on carbon tetrachloride-induced hepatic fibrosis in rats. BMC complementary and alternative medicine. 2018;18(1):1-8.
22. Kopjar N, Žunec S, Mendaš G, Micek V, Kašuba V, Mikolić A, et al. Evaluation of chlorpyrifos toxicity through a 28-day study: Cholinesterase activity, oxidative stress responses, parent compound/metabolite levels, and primary DNA damage in blood and brain tissue of adult male Wistar rats. Chemico-Biological Interactions. 2018;279:51-63.
23. Charan J, Kantharia N. How to calculate sample size in animal studies? Journal of Pharmacology and Pharmacotherapeutics. 2013;4(4):303-6.
24. Oruganti M, Gaidhani S. Routine bleeding techniques in laboratory rodents. International Journal of Pharmaceutical Sciences and Research. 2011;2(3):516.
25. Namisaki T, Moriya K, Kitade M, Takeda K, Kaji K, Okura Y, et al. Effect of combined farnesoid X receptor agonist and angiotensin II type 1 receptor blocker on hepatic fibrosis. Hepatology Communications. 2017;1(9):928-45.
26. Albasher G, Almeer R, Al-Otibi FO, Al-Kubaisi N, Mahmoud AM. Ameliorative effect of Beta vulgaris root extract on chlorpyrifos-induced oxidative stress, inflammation and liver injury in rats. Biomolecules. 2019;9(7):261.
27. Koenig F, Kilzer M, Hagl C, Thierfelder N. Successful decellularization of thick-walled tissue: Highlighting pitfalls and the need for a multifactorial approach. The International journal of artificial organs. 2019;42(1):17-24.
28. Suvik A, Effendy A. The use of modified Masson’s trichrome staining in collagen evaluation in wound healing study. Mal J Vet Res. 2012;3(1):39-47.
29. Almpanis Z, Demonakou M, Tiniakos D. Evaluation of liver fibrosis:“Something old, something new…”. Annals of gastroenterology: quarterly publication of the Hellenic Society of Gastroenterology. 2016;29(4):445.
30. Sule RO, Condon L, Gomes AV. A common feature of pesticides: oxidative stress—the role of oxidative stress in pesticide-induced toxicity. Oxidative Medicine and Cellular Longevity. 2022;2022.
31. Mdeni NL, Adeniji AO, Okoh AI, Okoh OO. Analytical evaluation of carbamate and organophosphate pesticides in human and environmental matrices: a review. Molecules. 2022;27(3):618.
32. Kunnaja P, Chansakaow S, Wittayapraparat A, Yusuk P, Sireeratawong S. In vitro antioxidant activity of Litsea martabanica root extract and its hepatoprotective effect on chlorpyrifos-induced toxicity in rats. Molecules. 2021;26(7):1906.
33. Liu D, Huang Y, Luo X. Farmers’ technology preference and influencing factors for pesticide reduction: evidence from Hubei Province, China. Environmental Science and Pollution Research. 2023;30(3):6424-34.
34. Wu Y-Q, Sun C-Y. Poison control services in China. Toxicology. 2004;198(1-3):279-84.
35. Marraffa JM, Cohen V, Howland MA. Antidotes for toxicological emergencies: a practical review. American Journal of Health-System Pharmacy. 2012;69(3):199-212.
36. Ghane T, Saberi S, Davoodabadi M. Descriptive analysis of recorded phone calls to Iran drug and poison information centers during 2011-2012. Asia Pacific Journal of Medical Toxicology. 2013;2(2):48-51.
37. Prajapati T, Prajapati K, Tandon R, Merchant S. Acute chemical and pharmaceutical poisoning cases treated in civil hospital, Ahmedabad: one year study. Asia Pacific Journal of Medical Toxicology. 2013;2(2):63-7.
38. Inam-ul-Haq M, Hyder S, Nisa T, Bibi S, Ismail S, Ibrahim Tahir M. Overview of biopesticides in Pakistan. Plant Growth Promoting Rhizobacteria (PGPR): Prospects for Sustainable Agriculture. 2019:255-68.
39. Khurram M, Mahmood N. Short communication-deliberate self-poisoning: experience at a medical unit. J Pak Med Assoc. 2008;58:455.
40. Siddiqui E, Razzak J, Naz F, Khan SJ. Factors associated with hydrocarbon ingestion in children. Journal of the Pakistan Medical Association. 2008;58(11):608.
41. Fatmi Z, Hadden WC, Razzak JA, Qureshi HI, Hyder AA, Pappas G. Incidence, patterns and severity of reported unintentional injuries in Pakistan for persons five years and older: results of the National Health Survey of Pakistan 1990–94. BMC public health. 2007;7(1):1-7.
42. Al-Arami AMJ, AL-Sanabani ASM. Histopathological Effects of Pesticide Imidacloprid Insecticide on the Liver in Male Rabbits. Ibn AL- Haitham Journal For Pure and Applied Sciences. 2021.
43. Yazdinezhad A, Abbasian MR, Hojjat Hosseini S, Naserzadeh P, Agh-Atabay A-H, Hosseini M-J. Protective effects of Ziziphora tenuior extract against chlorpyrifos induced liver and lung toxicity in rat: Mechanistic approaches in subchronic study. Environmental Toxicology. 2017;32:2191 - 202.
44. Ravikumar Y, Madhuri D, Lakshman MR, Gopalareddy A, Kalakumar B, Anilkumar B. Cadmium and Chlorpyrifos Induced Lipid Peroxidation in Brain, Liver and Kidney of Wistar Rats. Toxicology International. 2023.
45. Ragab MH, Laila A, Nahed SB, Henry SR. ASSESSMENT OF CURATIVE EFFECT OF USING STEM CELLS ON THE CONTROL OF PESTICIDE DAMAGING EFFECT ON LIVER. Journal of Environmental Sciences-china. 2017;39:23-39.
46. Wani H, Rehman S, Shoukat S, Kour N, Ayoub B. Patho-Morphological Changes in Liver, Kidney and Brain of Broiler Birds Due to Chlorpyrifos Intoxication. International Journal of Livestock Research. 2018;8:266-74.
47. Lasram MM, Annabi AB, El Elj N, Selmi S, Kamoun A, El-Fazaa S, et al. Metabolic disorders of acute exposure to malathion in adult Wistar rats. Journal of Hazardous Materials. 2009;163(2-3):1052-5.
48. Zhang Y, Jia Q, Hu C, Han M, Guo Q, Li S, et al. Effects of chlorpyrifos exposure on liver inflammation and intestinal flora structure in mice. Toxicology Research. 2021;10(1):141-9.
49. Shah B, Shah G. Antifibrotic effect of heparin on liver fibrosis model in rats. World journal of gastrointestinal pharmacology and therapeutics. 2012;3(6):86.
50. Nogueira CW, Borges LP, Souza ACG. Oral administration of diphenyl diselenide potentiates hepatotoxicity induced by carbon tetrachloride in rats. Journal of Applied Toxicology. 2009;29(2):156-64.
51. Czechowska G, Celinski K, Korolczuk A, Wojcicka G, Dudka J, Bojarska A, et al. The effect of the angiotensin II receptor, type 1 receptor antagonists, losartan and telmisartan, on thioacetamide-induced liver fibrosis in rats. J Physiol Pharmacol. 2016;67(4):575-86.
52. Murad H, Ahmed O, Ghabrah T, Gari M. Telmisartan self-nanoemulsifying drug delivery system, compared with standard telmisartan, more effectively improves hepatic fibrosis in rats. Dose-Response. 2020;18(4):1559325820982190.
53. Yang L, Bataller R, Dulyx J, Coffman TM, Ginès P, Rippe RA, et al. Attenuated hepatic inflammation and fibrosis in angiotensin type 1a receptor deficient mice. Journal of hepatology. 2005;43(2):317-23.
54. Novo E, di Bonzo LV, Cannito S, Colombatto S, Parola M. Hepatic myofibroblasts: a heterogeneous population of multifunctional cells in liver fibrogenesis. The international journal of biochemistry & cell biology. 2009;41(11):2089-93.
55. Henderson NC, Sheppard D. Integrin-mediated regulation of TGFβ in fibrosis. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2013;1832(7):891-6.
56. Rosenbloom J, Mendoza FA, Jimenez SA. Strategies for anti-fibrotic therapies. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2013;1832(7):1088-103.
57. Fujinaga Y, Kawaratani H, Kaya D, Tsuji Y, Ozutsumi T, Furukawa M, et al. Effective combination therapy of angiotensin-II receptor blocker and rifaximin for hepatic fibrosis in rat model of nonalcoholic steatohepatitis. International Journal of Molecular Sciences. 2020;21(15):5589.
58. Parreira NA, Ramalho FS, Augusto MJ, Silva DM, Prado CM, Júnior JE, et al. The comparative efficacy of renin-angiotensin system blockers in schistosomal hepatic fibrosis. Experimental parasitology. 2018;191:9-18.
2. Yu J, He J-Q, Chen D-Y, Pan Q-L, Yang J-F, Cao H-C, et al. Dynamic changes of key metabolites during liver fibrosis in rats. World Journal of Gastroenterology. 2019;25(8):941.
3. Li J, Zhao Y-R, Tian Z. Roles of hepatic stellate cells in acute liver failure: From the perspective of inflammation and fibrosis. World Journal of Hepatology. 2019;11(5):412.
4. Barry AE, Baldeosingh R, Lamm R, Patel K, Zhang K, Dominguez DA, et al. Hepatic stellate cells and hepatocarcinogenesis. Frontiers in Cell and Developmental Biology. 2020;8:709.
5. Bates J, Vijayakumar A, Ghoshal S, Marchand B, Yi S, Kornyeyev D, et al. Acetyl-CoA carboxylase inhibition disrupts metabolic reprogramming during hepatic stellate cell activation. Journal of Hepatology. 2020;73(4):896-905.
6. Haque S, Morris JC. Transforming growth factor-β: A therapeutic target for cancer. Human vaccines & immunotherapeutics. 2017;13(8):1741-50.
7. Mitchell AE, Colvin HM. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. 2010.
8. Zhao W, Wang X, Sun K-H, Zhou L. α-smooth muscle actin is not a marker of fibrogenic cell activity in skeletal muscle fibrosis. PloS one. 2018;13(1):e0191031.
9. Rockey DC, Du Q, Shi Z. Smooth muscle α-actin deficiency leads to decreased liver fibrosis via impaired cytoskeletal signaling in hepatic stellate cells. The American journal of pathology. 2019;189(11):2209-20.
10. Jallow MF, Awadh DG, Albaho MS, Devi VY, Thomas BM. Pesticide knowledge and safety practices among farm workers in Kuwait: results of a survey. International journal of environmental research and public health. 2017;14(4):340.
11. van den Dries MA, Pronk A, Guxens M, Spaan S, Voortman T, Jaddoe VW, et al. Determinants of organophosphate pesticide exposure in pregnant women: a population-based cohort study in the Netherlands. International journal of hygiene and environmental health. 2018;221(3):489-501.
12. Mbah Ntepe LJ, Habib R, Judith Laure N, Raza S, Nepovimova E, Kuca K, et al. Oxidative Stress and Analysis of Selected SNPs of ACHE (rs 2571598), BCHE (rs 3495), CAT (rs 7943316), SIRT1 (rs 10823108), GSTP1 (rs 1695), and Gene GSTM1, GSTT1 in Chronic Organophosphates Exposed Groups from Cameroon and Pakistan. International journal of molecular sciences. 2020;21(17):6432.
13. Karami-Mohajeri S, Ahmadipour A, Rahimi H-R, Abdollahi M. Adverse effects of organophosphorus pesticides on the liver: a brief summary of four decades of research. Arhiv za higijenu rada i toksikologiju. 2017;68(4):261-75.
14. Yassin MM, Al-Najjar MS. Hepatic and Renal Toxicity of Methamidophos in Male Domestic Rabbits: Physiological Aspect. Recent Adv Biol Med. 2020;6(1):12457.
15. Mikhail T, Aggour N, Awadallah R, Boulos M, El-Dessoukey E, Karima A. Acute toxicity of organophosphorus and organochlorine insecticides in laboratory animals. Zeitschrift für Ernährungswissenschaft. 1979;18(4):258-68.
16. Shim KY, Eom YW, Kim MY, Kang SH, Baik SK. Role of the renin-angiotensin system in hepatic fibrosis and portal hypertension. The Korean Journal of Internal Medicine. 2018;33(3):453.
17. Wu C-H, Mohammadmoradi S, Chen JZ, Sawada H, Daugherty A, Lu HS. Renin-angiotensin system and cardiovascular functions. Arteriosclerosis, thrombosis, and vascular biology. 2018;38(7):e108-e16.
18. Bataller R, Schwabe RF, Choi YH, Yang L, Paik YH, Lindquist J, et al. NADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is critical in hepatic fibrosis. The Journal of clinical investigation. 2003;112(9):1383-94.
19. Yokohama S, Tokusashi Y, Nakamura K, Tamaki Y, Okamoto S, Okada M, et al. Inhibitory effect of angiotensin II receptor antagonist on hepatic stellate cell activation in non-alcoholic steatohepatitis. World journal of gastroenterology: WJG. 2006;12(2):322.
20. Rimola A, Londoño M-C, Guevara G, Bruguera M, Navasa M, Forns X, et al. Beneficial effect of angiotensin-blocking agents on graft fibrosis in hepatitis C recurrence after liver transplantation. Transplantation. 2004;78(5):686-91.
21. Liu H, Zhang Z, Hu H, Zhang C, Niu M, Li R, et al. Protective effects of Liuweiwuling tablets on carbon tetrachloride-induced hepatic fibrosis in rats. BMC complementary and alternative medicine. 2018;18(1):1-8.
22. Kopjar N, Žunec S, Mendaš G, Micek V, Kašuba V, Mikolić A, et al. Evaluation of chlorpyrifos toxicity through a 28-day study: Cholinesterase activity, oxidative stress responses, parent compound/metabolite levels, and primary DNA damage in blood and brain tissue of adult male Wistar rats. Chemico-Biological Interactions. 2018;279:51-63.
23. Charan J, Kantharia N. How to calculate sample size in animal studies? Journal of Pharmacology and Pharmacotherapeutics. 2013;4(4):303-6.
24. Oruganti M, Gaidhani S. Routine bleeding techniques in laboratory rodents. International Journal of Pharmaceutical Sciences and Research. 2011;2(3):516.
25. Namisaki T, Moriya K, Kitade M, Takeda K, Kaji K, Okura Y, et al. Effect of combined farnesoid X receptor agonist and angiotensin II type 1 receptor blocker on hepatic fibrosis. Hepatology Communications. 2017;1(9):928-45.
26. Albasher G, Almeer R, Al-Otibi FO, Al-Kubaisi N, Mahmoud AM. Ameliorative effect of Beta vulgaris root extract on chlorpyrifos-induced oxidative stress, inflammation and liver injury in rats. Biomolecules. 2019;9(7):261.
27. Koenig F, Kilzer M, Hagl C, Thierfelder N. Successful decellularization of thick-walled tissue: Highlighting pitfalls and the need for a multifactorial approach. The International journal of artificial organs. 2019;42(1):17-24.
28. Suvik A, Effendy A. The use of modified Masson’s trichrome staining in collagen evaluation in wound healing study. Mal J Vet Res. 2012;3(1):39-47.
29. Almpanis Z, Demonakou M, Tiniakos D. Evaluation of liver fibrosis:“Something old, something new…”. Annals of gastroenterology: quarterly publication of the Hellenic Society of Gastroenterology. 2016;29(4):445.
30. Sule RO, Condon L, Gomes AV. A common feature of pesticides: oxidative stress—the role of oxidative stress in pesticide-induced toxicity. Oxidative Medicine and Cellular Longevity. 2022;2022.
31. Mdeni NL, Adeniji AO, Okoh AI, Okoh OO. Analytical evaluation of carbamate and organophosphate pesticides in human and environmental matrices: a review. Molecules. 2022;27(3):618.
32. Kunnaja P, Chansakaow S, Wittayapraparat A, Yusuk P, Sireeratawong S. In vitro antioxidant activity of Litsea martabanica root extract and its hepatoprotective effect on chlorpyrifos-induced toxicity in rats. Molecules. 2021;26(7):1906.
33. Liu D, Huang Y, Luo X. Farmers’ technology preference and influencing factors for pesticide reduction: evidence from Hubei Province, China. Environmental Science and Pollution Research. 2023;30(3):6424-34.
34. Wu Y-Q, Sun C-Y. Poison control services in China. Toxicology. 2004;198(1-3):279-84.
35. Marraffa JM, Cohen V, Howland MA. Antidotes for toxicological emergencies: a practical review. American Journal of Health-System Pharmacy. 2012;69(3):199-212.
36. Ghane T, Saberi S, Davoodabadi M. Descriptive analysis of recorded phone calls to Iran drug and poison information centers during 2011-2012. Asia Pacific Journal of Medical Toxicology. 2013;2(2):48-51.
37. Prajapati T, Prajapati K, Tandon R, Merchant S. Acute chemical and pharmaceutical poisoning cases treated in civil hospital, Ahmedabad: one year study. Asia Pacific Journal of Medical Toxicology. 2013;2(2):63-7.
38. Inam-ul-Haq M, Hyder S, Nisa T, Bibi S, Ismail S, Ibrahim Tahir M. Overview of biopesticides in Pakistan. Plant Growth Promoting Rhizobacteria (PGPR): Prospects for Sustainable Agriculture. 2019:255-68.
39. Khurram M, Mahmood N. Short communication-deliberate self-poisoning: experience at a medical unit. J Pak Med Assoc. 2008;58:455.
40. Siddiqui E, Razzak J, Naz F, Khan SJ. Factors associated with hydrocarbon ingestion in children. Journal of the Pakistan Medical Association. 2008;58(11):608.
41. Fatmi Z, Hadden WC, Razzak JA, Qureshi HI, Hyder AA, Pappas G. Incidence, patterns and severity of reported unintentional injuries in Pakistan for persons five years and older: results of the National Health Survey of Pakistan 1990–94. BMC public health. 2007;7(1):1-7.
42. Al-Arami AMJ, AL-Sanabani ASM. Histopathological Effects of Pesticide Imidacloprid Insecticide on the Liver in Male Rabbits. Ibn AL- Haitham Journal For Pure and Applied Sciences. 2021.
43. Yazdinezhad A, Abbasian MR, Hojjat Hosseini S, Naserzadeh P, Agh-Atabay A-H, Hosseini M-J. Protective effects of Ziziphora tenuior extract against chlorpyrifos induced liver and lung toxicity in rat: Mechanistic approaches in subchronic study. Environmental Toxicology. 2017;32:2191 - 202.
44. Ravikumar Y, Madhuri D, Lakshman MR, Gopalareddy A, Kalakumar B, Anilkumar B. Cadmium and Chlorpyrifos Induced Lipid Peroxidation in Brain, Liver and Kidney of Wistar Rats. Toxicology International. 2023.
45. Ragab MH, Laila A, Nahed SB, Henry SR. ASSESSMENT OF CURATIVE EFFECT OF USING STEM CELLS ON THE CONTROL OF PESTICIDE DAMAGING EFFECT ON LIVER. Journal of Environmental Sciences-china. 2017;39:23-39.
46. Wani H, Rehman S, Shoukat S, Kour N, Ayoub B. Patho-Morphological Changes in Liver, Kidney and Brain of Broiler Birds Due to Chlorpyrifos Intoxication. International Journal of Livestock Research. 2018;8:266-74.
47. Lasram MM, Annabi AB, El Elj N, Selmi S, Kamoun A, El-Fazaa S, et al. Metabolic disorders of acute exposure to malathion in adult Wistar rats. Journal of Hazardous Materials. 2009;163(2-3):1052-5.
48. Zhang Y, Jia Q, Hu C, Han M, Guo Q, Li S, et al. Effects of chlorpyrifos exposure on liver inflammation and intestinal flora structure in mice. Toxicology Research. 2021;10(1):141-9.
49. Shah B, Shah G. Antifibrotic effect of heparin on liver fibrosis model in rats. World journal of gastrointestinal pharmacology and therapeutics. 2012;3(6):86.
50. Nogueira CW, Borges LP, Souza ACG. Oral administration of diphenyl diselenide potentiates hepatotoxicity induced by carbon tetrachloride in rats. Journal of Applied Toxicology. 2009;29(2):156-64.
51. Czechowska G, Celinski K, Korolczuk A, Wojcicka G, Dudka J, Bojarska A, et al. The effect of the angiotensin II receptor, type 1 receptor antagonists, losartan and telmisartan, on thioacetamide-induced liver fibrosis in rats. J Physiol Pharmacol. 2016;67(4):575-86.
52. Murad H, Ahmed O, Ghabrah T, Gari M. Telmisartan self-nanoemulsifying drug delivery system, compared with standard telmisartan, more effectively improves hepatic fibrosis in rats. Dose-Response. 2020;18(4):1559325820982190.
53. Yang L, Bataller R, Dulyx J, Coffman TM, Ginès P, Rippe RA, et al. Attenuated hepatic inflammation and fibrosis in angiotensin type 1a receptor deficient mice. Journal of hepatology. 2005;43(2):317-23.
54. Novo E, di Bonzo LV, Cannito S, Colombatto S, Parola M. Hepatic myofibroblasts: a heterogeneous population of multifunctional cells in liver fibrogenesis. The international journal of biochemistry & cell biology. 2009;41(11):2089-93.
55. Henderson NC, Sheppard D. Integrin-mediated regulation of TGFβ in fibrosis. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2013;1832(7):891-6.
56. Rosenbloom J, Mendoza FA, Jimenez SA. Strategies for anti-fibrotic therapies. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2013;1832(7):1088-103.
57. Fujinaga Y, Kawaratani H, Kaya D, Tsuji Y, Ozutsumi T, Furukawa M, et al. Effective combination therapy of angiotensin-II receptor blocker and rifaximin for hepatic fibrosis in rat model of nonalcoholic steatohepatitis. International Journal of Molecular Sciences. 2020;21(15):5589.
58. Parreira NA, Ramalho FS, Augusto MJ, Silva DM, Prado CM, Júnior JE, et al. The comparative efficacy of renin-angiotensin system blockers in schistosomal hepatic fibrosis. Experimental parasitology. 2018;191:9-18.
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Jan 24, 2024
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Aftab Abbasi, Samreen Memon, & Salman Ahmed Farsi Kazi. (2024). ANTIFIBROTIC EFFECTS OF ANGIOTENSIN RECEPTOR BLOCKERS IN ORGANOPHOSPHATE (CHLORPYRIFOS) INDUCED LIVER FIBROSIS. Journal of Population Therapeutics and Clinical Pharmacology, 31(1), 1302–1315. https://doi.org/10.53555/jptcp.v31i1.4175
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Author Biographies
Aftab Abbasi
Associate Professor, Department of Anatomy, Isra University, Hyderabad - Pakistan
Samreen Memon
Professor, Chairperson, Department of Anatomy, Liaquat University of Medical and Health Sciences, Jamshoro - Pakistan
Salman Ahmed Farsi Kazi
Professor, Department of Forensic Medicine, Isra University, Hyderabad - Pakistan