POSSIBLE PROTECTIVE ROLE OF SODIUM SALICYLATE NANOEMULSION AND GINGER ON CISPLATIN‑INDUCED HEPATOTOXICITY IN RATS (BIOCHEMICAL AND HISTOPATHOLOGICAL STUDY)
Objective: To describe the preparation and characterization of nanoemulsion of sodium salicylate loaded butane tetracarboxylic acid (Bt-Sc-NPs). It also investigates the possible protective effects of Bt-Sc-NPs and\or medicinal plant ginger to evaluate the changes of liver functions, oxidative stress and histopathological investigations against cisplatin-induced hepatotoxicity.
Methods: Serum was used to determine alanine aminotransferase (ALT), aspartate aminotransferase (AST), δ-glutamyl transferase (δGT), serum human laminin (LN) and tissue inhibitors of metalloproteinase1 (TIMP1). Liver tissue samples collected from the rats were used for the measurement of malondialdehyde (MDA), nitric oxide (NO) and paraoxonase 1 (PON1).
Results: The beneficial effects of Bt-Sc-NPs with its anti-inflammatory effect and the medicinal ginger with its antioxidant effect were observed. Injection of rats with cisplatin significantly increased serum ALT, AST, ɤGT, TIMP1 and LN. It also increased cisplatin-induced oxidative stress by a significant elevation in liver MDA, NO content; however, a significant decrease of PON1 content. While protection with Bt-Sc-NPs or ginger significantly improved these parameters. In addition, combination of both Bt-Sc-NPs and ginger significantly induced a decrease in serum ALT, AST, ɤGT, TIMP1 and LN. It also reduced cisplatin-induced oxidative stress by the significant reduction in liver MDA, NO content and elevation of PON1 content much more than protection with Bt-Sc-NPs or ginger alone.
Conclusion: Bt-Sc-NPs were synthesized using nanoemulsion with the help of homogenization and ultra-sonication waves. Combination with both of Bt-Sc-NPs and ginger showed a hepatoprotective role in ameliorating cisplatin‑induced hepatotoxicity due to their anti-inflammatory and antioxidant effects.
2. Björnsson ES. Drug-induced liver injury: an overview over the most critical compounds. Arch Toxicol 2015;89:327-34.
3. Lahon K, Das S. Hepatoprotective activity of ocimum sanctum alcoholic leaf extract against paracetamol-induced liver damage in Albino rats. Pharmacogn Res 2011;3:13.
4. Alrashed AA, El-Kordy EA. Possible protective role of panax ginseng on cisplatin-induced hepatotoxicity in adult male albino rats (Biochemical and Histological Study). J Microscopy Ultrastructure 2019;7:84.
5. Burger H, Loos WJ, Eechoute K, Verweij J, Mathijssen RH, Wiemer EA. Drug transporters of platinum-based anticancer agents and their clinical significance. Drug Resistance Updates 2011;14:22-34.
6. Tayem Y, Johnson TR, Mann BE, Green CJ, Motterlini R. Protection against cisplatin-induced nephrotoxicity by a carbon monoxide-releasing molecule. Am J Physiol Renal Physiol 2006;290:F789-F794.?
7. Hussein A, Ahmed AA, Shouman SA, Sharawy S. Ameliorating effect of DL-?-lipoic acid against cisplatin-induced nephrotoxicity and cardiotoxicity in experimental animals. Drug Discoveries Ther 2012;6:147-56.
8. Pathak Y, Thassu D. Eds. Drug delivery nanoparticles formulation and characterization. Vol. 191. CRC Press; 2016.
9. Heeba GH, Abd-Elghany MI. Effect of combined administration of ginger (Zingiberofficinale roscoe) and atorvastatin on the liver of rats. Phytomedicine 2010;17:1076-81.
10. Aryaeian N, Tavakkoli H. Ginger and its effects on inflammatory diseases. Adv Food Technol Nutr Sci Open J 2015;1:97-101.
11. Mohamed NA, El-Naggar ME. Amifostine-based nanoemulsion as promising protective agent for nephrotoxicity. J Innovations Pharm Biol Sci 2018;5:38-45.
12. Ramesh G, Reeves WB. Salicylate reduces cisplatin nephrotoxicity by inhibition of tumor necrosis factor-?. Kidney Int 2004;65:490-8.
13. Reagan Shaw S, Nihal M, Ahmad N. Dose translation from animal to human studies revisited. FASEB J 2008;22:659-61.
14. Ruiz Larrea MB, Leal AM, Liza M, Lacort M, de Groot H. Antioxidant effects of estradiol and 2-hydroxyestradiol on iron-induced lipid peroxidation of rat liver microsomes. Steroids 1994;59:383-8.
15. Montgomery HA, Dymock JF. The determination of nitrite in water. Analyst 1961;86:414-6.
16. Higashino K, Takahashi Y, Yamamura Y. Release of phenyl acetate esterase from liver microsomes by carbon tetrachloride. Clin Chim Acta 1972;41:313-20.
17. Liebler DC, Guengerich FP. Elucidating mechanisms of drug-induced toxicity. Nat Rev Drug Discovery 2005;4:410-20.
18. Watkins PB, Seeff LB. Drug?induced liver injury: summary of a single topic clinical research conference. Hepatology 2006;43:618-31.
19. Palipoch S, Punsawad C, Koomhin P, Suwannalert P. Hepatoprotective effect of curcumin and alpha-tocopherol against cisplatin-induced oxidative stress. BMC Complement Altern Med 2014;14:111–8.
20. Omar HA, Mohamed WR, Arafa ESA, Shehata BA, El Sherbiny GA, Arab HH, et al. Hesperidin alleviates cisplatin-induced hepatotoxicity in rats without inhibiting its antitumor activity. Pharmacol Rep 2016;68:349-56.
21. Niu C, Ma M, Han X, Wang Z, Li H. Hyperin protects against cisplatin-induced liver injury in mice. Actacirurgicabrasileira 2017;32:633-40.
22. Haniadka R, Saxena A, Shivashankara AR, Fayad R, Palatty PL, Nazreth N, Baliga MS. Ginger protects the liver against the toxic effects of xenobiotic compounds: preclinical observations. J Nutr Food Sci 2013;3:1000226.
23. Medina J, Moreno Otero R. Pathophysiological basis for antioxidant therapy in chronic liver disease. Drugs 2005;65:2445-61.
24. Bentli R, Parlakpinar H, Polat A, Samdanci E, Sarihan ME, Sagir M. Molsidomine prevents cisplatin-induced hepatotoxicity. Arch Med Res 2013;44:521-8.
25. Siegmund SV, Brenner DA. Molecular pathogenesis of alcohol?induced hepatic fibrosis. Alcohol: Clin Exp Res 2005;29:102S-109S.
26. Siddaraju MN, Dharmesh SM. Inhibition of gastric H+, K+?ATPase and helicobacter pylori growth by phenolic antioxidants of Zingiberofficinale. Mol Nutr Food Res 2007;51:324-32.
27. Carnovale CE, Ronco MT. Role of nitric oxide in liver regeneration. Ann Hepatol 2015;11:636-47.
28. Kaltalioglu K, Coskun Cevher S. Potential of morin and hesperidin in the prevention of cisplatin-induced nephrotoxicity. Renal Failure 2016;38:1291-9.
29. Balabanli B, Coskun Cevher S. Alleviation of cisplatin-induced hepatotoxic damage: the synergistic effect of morin and hesperidin against oxidative stress. Res J Pharmacogn 2019;6:9-18.
30. Abdel Salam OM, Sleem AA, Youness ER, Mohammed NA, Omara EA. Bone marrow-derived protect against haloperidol-induced brain and liver damage in mice. Biomed Pharmacol J 2018;11:11-22.
31. Mansour HH, Hafez HF, Fahmy NM. Silymarin modulates cisplatin-induced oxidative stress and hepatotoxicity in rats. J Biochem Mol Biol 2006;39:656.
32. Al-Helaly LA. Studies on paraoxonase-1 isolated from amniotic fluid and its effect against cisplatin-induced hepatotoxicity and cardiotoxicity in rats. Rafidain J Sci 2018;27(2E):42-56.
33. Jeong WI, Do SH, Jeong DH, Hong IH, Park JK, Ran KM, et al. Kinetics of MMP-1 and MMP-3 produced by mast cells and macrophages in liver fibrogenesis of rat. Anticancer Res 2006;26(5A):3517-26.
34. Rosa H, Parise ER. Is there a place for serum laminin determination in patients with liver disease and cancer? World J Gastroenterol 2008;14:3628.
35. Kart A, Cigremis Y, Karaman M, Ozen H. Caffeic acid phenethyl ester (CAPE) ameliorates cisplatin-induced hepatotoxicity in rabbit. Exp Toxicol Pathol 2010;62:45-52.
36. Liu J, Liu Y, Habeebu SS, Klaassen CD. Metallothionein (MT)-null mice are sensitive to cisplatin-induced hepatotoxicity. Toxicol Appl Pharmacol 1998;149:24-31.
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