The Hepatoprotection Provided by Taurine and Glycine against Antineoplastic Drugs Induced Liver Injury in an Ex Vivo Model of Normothermic Recirculating Isolated Perfused Rat Liver

Document Type : Research(Original) Article

Authors

1 Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

2 Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Pharmacology and Toxicology Department, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.

3 Department of Pharmacology-Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.

4 Pharmacology and Toxicology Department, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.

5 Food and Drug Organization, Ministry of Health, Tehran, Iran.

6 Center of Experimental & Comparative Medicine, Shiraz University of Medical Sciences, Shiraz, Iran Department of Animal Science, School of Agriculture, Shiraz University, Shiraz, Iran

Abstract

Taurine (2-aminoethane sulfonic acid) is a non-protein amino acid found in high concentration in different tissues. Glycine (Amino acetic acid) is the simplest amino acid incorporated in the structure of proteins. Several investigations indicate the hepatoprotective properties of these amino acids. On the other hand, antineoplastic agents-induced serum transaminase elevation and liver injury is a clinical complication. The current investigation was designed to screen the possible hepatoprotective properties of taurine and glycine against antineoplastic drugs-induced hepatic injury in an ex vivo model of isolated perfused rat liver. Rat liver was perfused with different concentration (10 µM, 100 µM and 1000 µM) of antineoplastic drugs (Mitoxantrone, Cyclophosphamide, Cisplatin, 5‑Fluorouracil, Doxorubicin and Dacarbazine) via portal vein. Taurine and glycine were administered to drug-treated livers and liver perfusate samples were collected for biochemical measurements (ALT, LDH, AST, and K+). Markers of oxidative stress (reactive oxygen species formation, lipid peroxidation, total antioxidant capacity and glutathione) were also assessed in liver tissue. Antineoplastic drugs caused significant pathological changes in perfusate biochemistry. Furthermore, markers of oxidative stress were significantly elevated in drug‑treated livers. It was found that taurine (5 and 10 mM) and glycine (5 and 10 mM) administration significantly mitigated the biomarkers of liver injury and attenuated drug‑induced oxidative stress. Our data indicate that taurine and glycine supplementation might help as potential therapeutic options to encounter anticancer drugs-induced liver injury.

Keywords

References

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