Mechanism of hepatocellular damage in rat caused by low serum selenium

Abstract

The aim of this paper is to investigate the mechanism of hepatocellular damage in rats caused by low serum selenium. Thirty six rats were randomly divided into 2 groups: group A (fed with low-selenium diet from the Keshan Disease area with the content of selenium being 0.017 mg/kg); group B [fed with selenium-supplemented diet and 0.3 mg/L selenium (Na₂SeO₃) was added to the drinking water]. Both were respectively fed for 12 weeks. At the end of the 12^th week, the levels of serum selenium, glutathione peroxidase (GPX) and malondialdehyde (MDA) in hepatic tissue were measured; the hepatocellular ultrastructure and apoptosis were observed as well. The levels of serum selenium and GPX in group A were markedly lower than those in group B. MDA level in group A was significantly higher than that in group B. Under the electron microscope (EM), the mitochondria were remarkably changed in group A. The rate of liver cell apoptosis appeared much higher in group A as well. It indicated that the damage caused by selenium deficiency was through the process of oxidation. Selenium deficiency led to apoptosis of hepatocytes where oxidative damage to mitochondria might be the cause.

References

1. Jabłońska-Kaszewska I, Swiatkowska-Stodulska R, Łukasiak J, Dejneka W, Dorosz A, Dabrowska E, Falkiewicz B . Serumselenium levels in alcoholic liver disease. Med Sci Monit, 2003, 9(Suppl 3): 15–18
2. Liu S Y, Li T Y, Zhao Z, Man R Y, Wang F . Effects of selenium and alpha-tocopherolon liver damage induced by feeding grains from an endemic area ofKeshan disease in rats. Mol Cell Biochem, 1994, 132(2): 109–115. doi:10.1007/BF00926919
3. Thuluvath P J, Triger D R . Selenium in chronic liverdisease. J Hepatol, 1992, 14(2–3): 176–182. doi:10.1016/0168‐8278(92)90155‐I
4. Jüngst C, Cheng B, Gehrke R, Schmitz V, Nischalke H D, Ramakers J, Schramel P, Schirmacher P, Sauerbruch T, Caselmann W H . Oxidative damage is increased in human liver tissue adjacent to hepatocellularcarcinoma. Hepatology, 2004, 39(6): 1663–1672. doi:10.1002/hep.20241
5. Mandal A K, Sinha J, Mandal S, Mukhopadhyay S, Das N . Targeting of liposomal flavonoidto liver in combating hepatocellular oxidative damage. Drug Deliv, 2002, 9(3): 181–185. doi:10.1080/15227950290097615
6. Jeyabal P V, Syed M B, Venkataraman M, Sambandham J K, Sakthisekaran D . Apigenin inhibits oxidativestress-induced macromolecular damage in N-nitrosodiethylamine (NDEA)-inducedhepatocellular carcinogenesis in Wistar albino rats. Mol Carcinog, 2005, 44(1): 11–20. doi:10.1002/mc.20115
7. Jozanov-Stankov O, Demajo M, Djujić I, Mandić M . Seleniumintake as a modulator of responsiveness to oxidative stress. J Environ Pathol Toxicol Oncol, 1998, 17(3–4): 251–257
8. Doyen P, Bigot A, Vasseur P, Rodius F . Molecular cloningand expression study of pi-class glutathione S-transferase (pi-GST)and selenium-dependent glutathione peroxidase (Se-GPx) transcriptsin the freshwater bivalve Dreissena polymorpha. Comp Biochem Physiol C Toxicol Pharmacol, 2008, 147(1): 69–77. doi:10.1016/j.cbpc.2007.08.002
9. Baliga M S, Wang H, Zhuo P, Schwartz J L, Diamond A M . Selenium and GPx-1 overexpressionprotect mammalian cells against UV-induced DNA damage. Biol Trace Elem Res, 2007, 115(3): 227–242. doi:10.1007/BF02685998
10. Turturro F, Friday E, Welbourne T . Hyperglycemia regulates thioredoxin-ROS activity throughinduction of thioredoxin-interacting protein (TXNIP) in metastaticbreast cancer-derived cells MDA-MB-231. BMC Cancer, 2007, 7: 96. doi: 10.1186/1471‐2407‐7‐96
11. Lin C H, Lin P H . Induction of ROS formation,poly(ADP-ribose) polymerase-1 activation, and cell death by PCB126and PCB153 in human T47D and MDA-MB-231 breast cancer cells. Chem Biol Interact, 2006, 162(2): 181–194. doi:10.1016/j.cbi.2006.06.009
12. Gawel S, Wardas M, Niedworok E, Wardas P . Malondialdehyde(MDA) as a lipid peroxidation marker. WiadLek, 2004, 57(9–10): 453–455
13. Newmeyer D D, Ferguson-Miller S . Mitochondria: releasing powerfor life and unleashing the machineries of death. Cell, 2003, 112(4): 481–490. doi:10.1016/S0092‐8674(03)00116‐8
14. Indo H P, Davidson M, Yen H C, Suenaga S, Tomita K, Nishii T, Higuchi M, Koga Y, Ozawa T, Majima H J . Evidenceof ROS generation by mitochondria in cells with impaired electrontransport chain and mitochondrial DNA damage. Mitochondrion, 2007, 7(1–2): 106–118. doi:10.1016/j.mito.2006.11.026
15. Scherz-Shouval R, Elazar Z . ROS, mitochondria and theregulation of autophagy. Trends Cell Biol, 2007, 17(9): 422–427. doi:10.1016/j.tcb.2007.07.009
16. Linford N J, Schriner S E, Rabinovitch P S . Oxidative damage and aging: spotlight on mitochondria. Cancer Res, 2006, 66(5): 2497–2499. doi:10.1158/0008‐5472.CAN‐05‐3163
17. Pessayre D, Mansouri A, Haouzi D, Fromenty B . Hepatotoxicitydue to mitochondrial dysfunction. CellBiol Toxicol, 1999, 15(6): 367–373. doi:10.1023/A:1007649815992
18. Yang J C, Cortopassi G A . Induction of the mitochondrialpermeability transition causes release of the apoptogenic factor cytochromec. Free Radic Biol Med, 1998, 24(4): 624–631. doi:10.1016/S0891‐5849(97)00367‐5
19. Reid A B, Kurten R C, McCullough S S, Brock R W, Hinson J A . Mechanisms of acetaminophen-induced hepatotoxicity:role of oxidative stress and mitochondrial permeability transitionin freshly isolated mouse hepatocytes. J Pharmacol Exp Ther, 2005, 312(2): 509–516. doi:10.1124/jpet.104.075945
20. Kowaltowski A J, Castilho R F, Vercesi A E . Mitochondrial permeability transition and oxidative stress. FEBS Lett, 2001, 495(1–2): 12–15. doi:10.1016/S0014‐5793(01)02316‐X