Effect of Dichloromethylene Diphosphonate on Liver Regeneration Following Thioacetamide-induced Necrosis in Rats

Overview

Journal World J Hepatol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2013 Jul 31

PMID 23898371

Citations 2

Authors

Mirandeli Bautista

Maria Angeles Gomez Del Rio

Juana Benedi

Maria Isabel Sanchez-Reus

Jose A Morales-Gonzalez

Ana Maria Tellez-Lopez

Maricela Lopez-Orozco

Affiliations

Soon will be listed here.

Abstract

Aim: To study the effect of dichloromethylene diphosphonate (DMDP), a selective Kupffer cell toxicant in reference to liver damage and postnecrotic liver regeneration in rats induced by sublethal dose thioacetamide (TA).

Methods: Rats, intravenously (iv) pre-treated with a single dose of DMDP (10 mg/kg), were intraperitoneally (ip) injected with TA 6.6 mmol/kg (per 500 mg/kg body weight). Hepatocytes were isolated from rats at 0, 24, 48 and 72 h following TA intoxication and blood and liver samples were obtained. To evaluate the mechanisms involved in the postnecrotic regenerative state, DNA distribution and ploidy time course were assayed in isolated hepatocytes. Circulating cytokine tumor necrosis factor-alpha (TNF-α) was assayed in serum and determined by reverse transcriptase-polymerase chain reaction in liver extract.

Results: The effect of DMDP induced noticeable changes in postnecrotic regeneration, causing an increased percentage of hepatocytes in the cell cycle S phase. The increase at 24 h in S1 population in rats pretreated with DMDP + TA was significantly (P < 0.05) different compared with that of the TA group (18.07% vs 8.57%). Hepatocytes increased their proliferation as a result of these changes. Also, TNF-α expression and serum level were increased in rats pre-treated with DMDP. Thus, DMDP pre-treatment reduced TA-induced liver injury and accelerated postnecrotic liver regeneration.

Conclusion: These results demonstrate that Kupffer cells are involved in TA-induced liver, as well as in postnecrotic proliferative liver states.

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References

Sanz N, Diez-Fernandez C, Alvarez A, Cascales M . Age-related changes on parameters of experimentally-induced liver injury and regeneration. Toxicol Appl Pharmacol. 1999; 154(1):40-9. DOI: 10.1006/taap.1998.8541. View

Diez-Fernandez C, Bosca L, Alvarez A, Cascales M . Relationship between genomic DNA ploidy and parameters of liver damage during necrosis and regeneration induced by thioacetamide. Hepatology. 1993; 18(4):912-8. DOI: 10.1002/hep.1840180424. View

Meijer C, Wiezer M, Diehl A, Schouten H, Meijer S, van Rooijen N . Kupffer cell depletion by CI2MDP-liposomes alters hepatic cytokine expression and delays liver regeneration after partial hepatectomy. Liver. 2000; 20(1):66-77. DOI: 10.1034/j.1600-0676.2000.020001066.x. View

BAUMAN J, Liu J, Liu Y, Klaassen C . Increase in metallothionein produced by chemicals that induce oxidative stress. Toxicol Appl Pharmacol. 1991; 110(2):347-54. DOI: 10.1016/s0041-008x(05)80017-1. View

Shiratori Y, Kiriyama H, Fukushi Y, Nagura T, Takada H, Hai K . Modulation of ischemia-reperfusion-induced hepatic injury by Kupffer cells. Dig Dis Sci. 1994; 39(6):1265-72. DOI: 10.1007/BF02093792. View

Mehendale H, Roth R, Gandolfi A, Klaunig J, Lemasters J, Curtis L . Novel mechanisms in chemically induced hepatotoxicity. FASEB J. 1994; 8(15):1285-95. DOI: 10.1096/fasebj.8.15.8001741. View

Bautista M, Andres D, Cascales M, Morales-Gonzalez J, Sanchez-Reus M, Madrigal-Santillan E . Role of Kupffer cells in thioacetamide-induced cell cycle dysfunction. Molecules. 2011; 16(10):8319-31. PMC: 6264164. DOI: 10.3390/molecules16108319. View

Fujita J, Marino M, Wada H, Jungbluth A, Mackrell P, Rivadeneira D . Effect of TNF gene depletion on liver regeneration after partial hepatectomy in mice. Surgery. 2001; 129(1):48-54. DOI: 10.1067/msy.2001.109120. View

Decker K . Biologically active products of stimulated liver macrophages (Kupffer cells). Eur J Biochem. 1990; 192(2):245-61. DOI: 10.1111/j.1432-1033.1990.tb19222.x. View

10.

van Rooijen N, Sanders A . Liposome mediated depletion of macrophages: mechanism of action, preparation of liposomes and applications. J Immunol Methods. 1994; 174(1-2):83-93. DOI: 10.1016/0022-1759(94)90012-4. View

11.

Lazar Jr G, Lazar G, Kaszaki J, Olah J, Kiss I, HUSZTIK E . Inhibition of anaphylactic shock by gadolinium chloride-induced Kupffer cell blockade. Agents Actions. 1994; 41 Spec No:C97-8. DOI: 10.1007/BF02007784. View

12.

Chomczynski P, Sacchi N . Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987; 162(1):156-9. DOI: 10.1006/abio.1987.9999. View

13.

Blazka M, Wilmer J, Holladay S, Wilson R, Luster M . Role of proinflammatory cytokines in acetaminophen hepatotoxicity. Toxicol Appl Pharmacol. 1995; 133(1):43-52. DOI: 10.1006/taap.1995.1125. View

14.

Badger D, Kuester R, Sauer J, Sipes I . Gadolinium chloride reduces cytochrome P450: relevance to chemical-induced hepatotoxicity. Toxicology. 1997; 121(2):143-53. DOI: 10.1016/s0300-483x(97)00065-6. View

15.

RAI R, Yang S, McClain C, Karp C, Klein A, Diehl A . Kupffer cell depletion by gadolinium chloride enhances liver regeneration after partial hepatectomy in rats. Am J Physiol. 1996; 270(6 Pt 1):G909-18. DOI: 10.1152/ajpgi.1996.270.6.G909. View

16.

Schiedner G, Hertel S, Johnston M, Dries V, van Rooijen N, Kochanek S . Selective depletion or blockade of Kupffer cells leads to enhanced and prolonged hepatic transgene expression using high-capacity adenoviral vectors. Mol Ther. 2003; 7(1):35-43. DOI: 10.1016/s1525-0016(02)00017-5. View

17.

van Rooijen N, Sanders A . Kupffer cell depletion by liposome-delivered drugs: comparative activity of intracellular clodronate, propamidine, and ethylenediaminetetraacetic acid. Hepatology. 1996; 23(5):1239-43. DOI: 10.1053/jhep.1996.v23.pm0008621159. View

18.

Harstad E, Klaassen C . Gadolinium chloride pretreatment prevents cadmium chloride-induced liver damage in both wild-type and MT-null mice. Toxicol Appl Pharmacol. 2002; 180(3):178-85. DOI: 10.1006/taap.2002.9385. View

19.

Sanz N, Diez-Fernandez C, Alvarez A, Cascales M . Necrogenic and regenerative responses of liver of newly weaned rats against a sublethal dose of thioacetamide. Biochim Biophys Acta. 1998; 1384(1):66-78. DOI: 10.1016/s0167-4838(97)00218-5. View

20.

Theocharis S, Kanelli H, Margeli A, Spiliopoulou C, Koutselinis A . Metallothionein and heat shock protein expression during acute liver injury and regeneration in rats. Clin Chem Lab Med. 2001; 38(11):1137-40. DOI: 10.1515/CCLM.2000.172. View