Alpha-lipoic acid attenuates iron-overload-induced structural changes in the liver of the laboratory mouse (Mus musculus)

Year 2018, Volume: 12 Issue: 3, 118 - 123, 31.12.2018

William Sibuor , Fidel Gwala , Jeremiah Munguti Moses Obimbo

Abstract

Objectives: The role of alpha-lipoic acid in the amelioration of
iron overload-induced hepatic damage remains largely under-explored.
 Therefore, this paper aimed at describing the structural effects of alpha
lipoic acid on the liver following iron overload in mice.

Methods: After ethical approval, a total of 24 male mice were used. Twenty
 mice were randomly divided into 2 groups: A and B. Group A rats received
50mg/kg of iron dextran intraperitoneally daily for 49 days while those in
group B received a daily oral dose of 100mg/kg alpha lipoic acid by gavage in
addition to the treatment in A. Four mice were used as normal controls. At the
endpoint of the experiment, the livers were harvested and studied for iron
deposition, parenchymal histoarchitecture and hepatocyte densities.
Photomicrographs were taken using a digital photomicroscope for morphometric
analysis.
Results: Treatment of mice with iron led to a distortion of the
histoarchitecture of the liver which was attenuated with co-administration of
alpha lipoic acid. Additionally, co-treatment of iron with alpha lipoic acid
resulted in significant lowering of hepatic iron deposition (p<0.001),
reduction in leukocyte infiltration and significantly greater hepatocyte
densities (p<0.001).

Conclusion: Alpha-lipoic acid appreciably attenuates the
structural damage in the liver induced by iron overload.

 

Keywords

Alpha-lipoic acid, Iron, Liver

References

• 1. Hentze MW, Muckenthaler MU, Galy B, Camaschella C. Two to tango: regulation of Mammalian iron metabolism. Cell 2010; 142(1):24-38.
• 2. Siddique A, Kowdley KV. Review article: the iron overload syndromes. Aliment Pharmacol Ther 2012; 35(8):876-893.
• 3. Kohgo Y, Ikuta K, Ohtake T, Torimoto Y, Kato J. Body iron metabolism and pathophysiology of iron overload. Int J Hematol 2008; 88(1):7-15.
• 4. Hershko C. Iron chelation therapy. Springer Science & Business Media; 2012. 28-36.
• 5. Sheth S. Iron chelation: an update Curr Opin Hematol 2014; 21(3):179-185.
• 6. Brissot P. Optimizing the diagnosis and the treatment of iron overload diseases. Expert Rev Gastroenterol Hepatol 2016; 10(3):359-370.7. Mobarra N, Shanaki M, Ehteram H, Nasiri H, Sahmani M, Saeidi M, Goudarzi M, Pourkarim H, Azad M. A review on iron chelators in treatment of iron overload syndromes Int J Hematol Oncol Stem Cell Res 2016; 10(4):239-247.
• 8. Assi TB, Baz E. Current applications of therapeutic phlebotomy. Blood Transfus. 2014; 12:75-83.
• 9. Ziegler D, Nowak H, Kempler P, Vargha P, Low PA. Treatment of symptomatic diabetic polyneuropathy with the antioxidant α‐lipoic acid: a meta‐analysis. Diabet Med 2004; 21(2):114-121.
• 10. Goralska M, Dackor R, Holley B, McGahan MC. Alpha lipoic acid changes iron uptake and storage in lens epithelial cells. Exp Eye Res 2003; 76(2):241-248.
• 11. Suh JH, Moreau R, Heath SH, Hagen TM. Dietary supplementation with (R)-α-lipoic acid reverses the age-related accumulation of iron and depletion of antioxidants in the rat cerebral cortex. Redox Rep 2005; 10(1):52-60.
• 12. Zhang Y, Zhang Y, Xie Y, Gao Y, Ma J, Yuan J, Li J, Wang J, Li L, Zhang J, Chu L. Multitargeted inhibition of hepatic fibrosis in chronic iron-overloaded mice by Salvia miltiorrhiza. J Ethnopharmacol 2013; 148(2):671-681.
• 13. Budin SB, Othman F, Louis SR, Bakar MA, Radzi M, Osman K, Das S, Mohamed J. Effect of alpha lipoic acid on oxidative stress and vascular wall of diabetic rats. Rom J Morphol Embryol 2009; 50(1):23-30.
• 14. Ahmadvand H, Jamor P. Effects of alpha lipoic acid on level of NO and MPO activity in diabetic rats. Ann Res Antioxid 2017; 2(2):4-7.
• 15. Marcos R, Monteiro RA, Rocha E. The use of design‐based stereology to evaluate volumes and numbers in the liver: a review with practical guidelines. J Anat 2012; 220(4):303-317.
• 16. Mandarim-de-Lacerda CA. Stereological tools in biomedical research. An Acad Bras Cienc 2003; 75(4):469-486.
• 17. Gundersen HJ, Bagger P, Bendtsen TF, Evans SM, Korbo LX, Marcussen N, Møller A, Nielsen K, Nyengaard JR, Pakkenberg B, Sørensen FB. The new stereological tools: disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis. APMIS 1988; 96(7‐12):857-881.
• 18. Bancroft JD, Cook HC. Manual of histological techniques and their diagnostic application. Churchill Livingstone; 1994.35-67.
• 19. Gao Y, Wang N, Zhang Y, Ma Z, Guan P, Ma J, Zhang Y, Zhang X, Wang J, Zhang J, Chu L. Mechanism of protective effects of Danshen against iron overload-induced injury in mice. J Ethnopharmacol 2013; 145(1):254-260.
• 20. Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TM. Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim Biophys Acta 2009; 1790(10):1149-1160.
• 21. Yatmark P, Morales NP, Chaisri U, Wichaiyo S, Hemstapat W, Srichairatanakool S, Svasti S, Fucharoen S. Iron distribution and histopathological characterization of the liver and heart of β-thalassemic mice with parenteral iron overload: Effects of deferoxamine and deferiprone. Exp Toxicol Pathol 2014; 66(7):333-343.
• 22. Altintoprak N, Aydin S, Sanli A, Bilmez ZE, Kösemihal E. The Protective Effect of Intratympanic Alpha Lipoic Acid on Cisplatin-Induced Ototoxicity on Rats. J Int Adv Otol 2014; 10(3):217-221.
• 23. Fernandes MS, Rissi TT, Zuravski L, Mezzomo J, Vargas CR, Folmer V, Soares FA, Manfredini V, Ahmed M, Puntel RL. Oxidative stress and labile plasmatic iron in anemic patients following blood therapy. World J Exp Med 2014; 4(3):38-45.
• 24. Hazra B, Sarkar R, Ghate NB, Chaudhuri D, Mandal N. Study of the protective effects of Katha (heartwood extract of Acacia catechu) in liver damage induced by iron overload. J Environ Pathol Toxicol Oncol 2013; 32(3):229-240.
• 25. Sarkar R, Hazra B, Mandal N. Amelioration of iron overload-induced liver toxicity by a potent antioxidant and iron chelator, Emblica officinalis Gaertn. Toxicol Ind Health 2015; 31(7):656-669.
• 26. Al-Attar AM. Physiological and Histopathological Investigations on the Effects of 𝛼-Lipoic Acid in Rats Exposed to Malathion. BioMed Res Int 2010; 2010:203503.
• 27. Zhao L, Wang C, Song D, Li Y, Song Y, Su G, Dunaief JL. Systemic administration of the antioxidant/iron chelator α-lipoic acid protects against light-induced photoreceptor degeneration in the mouse retina. Invest Ophthalmol Vis Sci 2014; 55(9):5979-5988.
• 28. Rezk RG, Abdel-Rahman NA. Protective effects of lipoic acid against oxidative stress induced by lead acetate and gamma-irradiation in the kidney and lung in albino rats. Arab J Nucl Sci Applic 2013; 46:324-337.
• 29. Biewenga GP, Haenen GR, Bast A. The pharmacology of the antioxidant lipoic acid. Gen Pharmacol 1997; 29(3):315-331.
• 30. Suh JH, Wang H, Liu RM, Liu J, Hagen TM. (R)-α-Lipoic acid reverses the age-related loss in GSH redox status in post-mitotic tissues: evidence for increased cysteine requirement for GSH synthesis. Arch Biochem Biophys 2004; 423(1):126-135.
• 31. Zhang J, Zhou X, Wu W, Wang J, Xie H, Wu Z. Regeneration of glutathione by α-lipoic acid via Nrf2/ARE signaling pathway alleviates cadmium-induced HepG2 cell toxicity. Environ Toxicol Pharmacol 2017; 51:30-37.
• 32. Liu D, He H, Yin D, Que A, Tang L, Liao Z, Huang Q, He M. Mechanism of chronic dietary iron overload induced liver damage in mice. Mol Med Rep 2013; 7(4):1173-1179.