Acute Bone Damage Through Liver-bone Axis Induced by Thioacetamide in Rats

Overview

Journal BMC Pharmacol Toxicol

Publisher Biomed Central

Specialty Pharmacology

Date 2022 May 7

PMID 35526079

Authors

Xiaoli Jin

Yang Li

Jianghua Li

Linyan Cheng

Yetao Yao

Hao Shen

Bili Wang

Jun Ren

Hang Ying

Jian Xu

Affiliations

Soon will be listed here.

Abstract

Background: Thioacetamide (TAA) is used in various fields, such as synthetic drugs, organic chemical synthesis, and materials chemistry. TAA is mainly used to establish animal liver injury models and other organ damage models to explore their mechanisms for helping patients with liver disease. Liver damage can lead to abnormal expression of some enzymes in the serum, so we detected the appropriate enzyme levels in the serum of SD rats to verify the damage of TAA to the liver. More importantly, TAA caused bone damage is barely understood. Therefore, our research aims to establish a rat model reflecting the acute bone damage injury caused by TAA.

Methods: The SD rats were intraperitoneally injected with normal saline (0.9%) or TAA (200 mg/kg, 400 mg/kg) for 1 month (once the other day). After the last intraperitoneal injection, serum samples from rats were used for biochemical tests. Masson staining is used to detect liver damage, and micro-CT is used to detect the changes in bone. Moreover, the three-point bending experiment was used to detect the force range of the hind limbs of SD rats.

Results: Compared with the control group, after the intraperitoneal injection of TAA, the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), uric acid (UA), total bile acid (TBA), alkaline phosphatase (ALP), carbamide (UREA) and creatinine (CREA) rose sharply, while the levels of serum content of total protein (TP), lactate dehydrogenase (LDH), calcium (Ca) and phosphorus (P) were severely reduced. After TAA administration, collagen fibers were deposited and liver fibrosis was obvious. Micro-CT results showed that the bone surface, tissue surface, bone volume, and tissue volume of rats with an intraperitoneal injection of TAA were significantly reduced. In addition, the bones of rats with an intraperitoneal injection of TAA can resist less pressure and are prone to fractures.

Conclusions: TAA can cause liver damage in SD rats, which is explained by the changes in serum biochemical indicators and the deposition of liver collagen. More importantly, TAA can reduce bone mineral density and increase the separation of bone trabeculae in SD rats, and finally lead to bone injury. This suggests that TAA may become an ideal model to investigate abnormal bone metabolism after liver injury.

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References

Rouillard S, Lane N . Hepatic osteodystrophy. Hepatology. 2000; 33(1):301-7. DOI: 10.1053/jhep.2001.20533. View

Tunon M, Alvarez M, Culebras J, Gonzalez-Gallego J . An overview of animal models for investigating the pathogenesis and therapeutic strategies in acute hepatic failure. World J Gastroenterol. 2009; 15(25):3086-98. PMC: 2705730. DOI: 10.3748/wjg.15.3086. View

Chilakapati J, Shankar K, Korrapati M, Hill R, Mehendale H . Saturation toxicokinetics of thioacetamide: role in initiation of liver injury. Drug Metab Dispos. 2005; 33(12):1877-85. DOI: 10.1124/dmd.105.005520. View

Moschen A, Kaser A, Stadlmann S, Millonig G, Kaser S, Muhllechner P . The RANKL/OPG system and bone mineral density in patients with chronic liver disease. J Hepatol. 2005; 43(6):973-83. DOI: 10.1016/j.jhep.2005.05.034. View

Neal R, Halpert J . Toxicology of thiono-sulfur compounds. Annu Rev Pharmacol Toxicol. 1982; 22:321-39. DOI: 10.1146/annurev.pa.22.040182.001541. View

Compston J . Hepatic osteodystrophy: vitamin D metabolism in patients with liver disease. Gut. 1986; 27(9):1073-90. PMC: 1433796. DOI: 10.1136/gut.27.9.1073. View

Guanabens N, Cerda D, Monegal A, Pons F, Caballeria L, Peris P . Low bone mass and severity of cholestasis affect fracture risk in patients with primary biliary cirrhosis. Gastroenterology. 2010; 138(7):2348-56. DOI: 10.1053/j.gastro.2010.02.016. View

Jackson R, LaCroix A, Gass M, Wallace R, Robbins J, Lewis C . Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med. 2006; 354(7):669-83. DOI: 10.1056/NEJMoa055218. View

Iwamoto J, Seki A, Sato Y, Matsumoto H, Takeda T, Yeh J . Effect of vitamin K2 on cortical and cancellous bone mass and hepatic lipids in rats with combined methionine-choline deficiency. Bone. 2011; 48(5):1015-21. DOI: 10.1016/j.bone.2011.02.015. View

10.

Li Y, Gong X, Liu M, Peng C, Li P, Wang Y . Investigation of Liver Injury of Thunb. in Rats by Metabolomics and Traditional Approaches. Front Pharmacol. 2017; 8:791. PMC: 5672018. DOI: 10.3389/fphar.2017.00791. View

11.

Nussler A, Wildemann B, Freude T, Litzka C, Soldo P, Friess H . Chronic CCl4 intoxication causes liver and bone damage similar to the human pathology of hepatic osteodystrophy: a mouse model to analyse the liver-bone axis. Arch Toxicol. 2014; 88(4):997-1006. DOI: 10.1007/s00204-013-1191-5. View

12.

Waters N, Waterfield C, Farrant R, Holmes E, Nicholson J . Metabonomic deconvolution of embedded toxicity: application to thioacetamide hepato- and nephrotoxicity. Chem Res Toxicol. 2005; 18(4):639-54. DOI: 10.1021/tx049869b. View

13.

Takeda E, Yamamoto H, Yamanaka-Okumura H, Taketani Y . Dietary phosphorus in bone health and quality of life. Nutr Rev. 2012; 70(6):311-21. DOI: 10.1111/j.1753-4887.2012.00473.x. View

14.

FITZHUGH O, Nelson A . Liver Tumors in Rats Fed Thiourea or Thioacetamide. Science. 1948; 108(2814):626-8. DOI: 10.1126/science.108.2814.626. View

15.

Nakano A, Kanda T, Abe H . Bone changes and mineral metabolism disorders in rats with experimental liver cirrhosis. J Gastroenterol Hepatol. 1996; 11(12):1143-54. DOI: 10.1111/j.1440-1746.1996.tb01843.x. View

16.

Chen X, Wang Z, Duan N, Zhu G, Schwarz E, Xie C . Osteoblast-osteoclast interactions. Connect Tissue Res. 2017; 59(2):99-107. PMC: 5612831. DOI: 10.1080/03008207.2017.1290085. View

17.

Li Y, Chen M, Zhao Y, Li M, Qin Y, Cheng S . Advance in Drug Delivery for Ageing Skeletal Muscle. Front Pharmacol. 2020; 11:1016. PMC: 7360840. DOI: 10.3389/fphar.2020.01016. View

18.

Okuyama H, Nakamura H, Shimahara Y, Uyama N, Kwon Y, Kawada N . Overexpression of thioredoxin prevents thioacetamide-induced hepatic fibrosis in mice. J Hepatol. 2005; 42(1):117-23. DOI: 10.1016/j.jhep.2004.09.020. View

19.

Al-Bader A, Mathew T, Khoursheed M, Asfar S, Al-Sayer H, Dashti H . Thioacetamide toxicity and the spleen: histological and biochemical analysis. Anat Histol Embryol. 2000; 29(1):3-8. DOI: 10.1046/j.1439-0264.2000.00207.x. View

20.

KLEINFELD R . Early changes in rat liver and kidney cells induced by thioacetamide. Cancer Res. 1957; 17(10):954-62. View