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Protective effects of tiopronin against high fat diet-induced non-alcoholic steatohepatitis in rats.
Acta Pharmacol Sin. 2012 Jun; 33(6):791-7.AP

Abstract

AIM

To study the protective effects of tiopronin against high fat diet-induced non-alcoholic steatohepatitis in rats.

METHODS

Male Sprague-Dawley rats were given a high-fat diet for 10 weeks. The rats were administered tiopronin (20 mg/kg) or a positive control drug ursodeoxycholic acid (UDCA, 15 mg/kg) via gavage daily from week 5 to week 10. After the rats were sacrificed, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), free fatty acids (FFA), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C), and liver homogenate FFA, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were measured using commercial analysis kits. The expression levels of CYP2E1 mRNA and protein were determined using RT-PCR and immunoblot assays, respectively.

RESULTS

Tiopronin significantly lowered both the serum ALT and AST levels, while only the serum ALT level was lowered by UDCA. Tiopronin significantly decreased the serum and liver levels of TG, TC and FFA as well as the serum LDL-C level, and increased the serum HDL-C level, while UDCA decreased the serum and liver TC levels as well as the serum LDL-C level, but did not change the serum levels of TG, FFA and HDL-C. Tiopronin apparently ameliorated the hepatocyte degeneration and the infiltration of inflammatory cells in the livers, but UDCA did not affect the pathological features of the livers. Both tiopronin and UDCA ameliorated the mitochondrial abnormality in the livers. The benefits of tiopronin were associated with increased SOD and GSH-Px activities, and with decreased MDA activity and CYP2E1 expression in the livers.

CONCLUSION

Tiopronin exerts protective effects against non-alcoholic steatohepatitis in rats, which may be associated with its antioxidant properties and regulation of lipid metabolism.

Authors+Show Affiliations

School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22543705

Citation

Wang, Jian-qing, et al. "Protective Effects of Tiopronin Against High Fat Diet-induced Non-alcoholic Steatohepatitis in Rats." Acta Pharmacologica Sinica, vol. 33, no. 6, 2012, pp. 791-7.
Wang JQ, Zou YH, Huang C, et al. Protective effects of tiopronin against high fat diet-induced non-alcoholic steatohepatitis in rats. Acta Pharmacol Sin. 2012;33(6):791-7.
Wang, J. Q., Zou, Y. H., Huang, C., Lu, C., Zhang, L., Jin, Y., Lü, X. W., Liu, L. P., & Li, J. (2012). Protective effects of tiopronin against high fat diet-induced non-alcoholic steatohepatitis in rats. Acta Pharmacologica Sinica, 33(6), 791-7. https://doi.org/10.1038/aps.2012.19
Wang JQ, et al. Protective Effects of Tiopronin Against High Fat Diet-induced Non-alcoholic Steatohepatitis in Rats. Acta Pharmacol Sin. 2012;33(6):791-7. PubMed PMID: 22543705.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective effects of tiopronin against high fat diet-induced non-alcoholic steatohepatitis in rats. AU - Wang,Jian-qing, AU - Zou,Yu-hong, AU - Huang,Cheng, AU - Lu,Chao, AU - Zhang,Lei, AU - Jin,Yong, AU - Lü,Xiong-wen, AU - Liu,Li-ping, AU - Li,Jun, Y1 - 2012/04/30/ PY - 2012/5/1/entrez PY - 2012/5/1/pubmed PY - 2012/10/16/medline SP - 791 EP - 7 JF - Acta pharmacologica Sinica JO - Acta Pharmacol Sin VL - 33 IS - 6 N2 - AIM: To study the protective effects of tiopronin against high fat diet-induced non-alcoholic steatohepatitis in rats. METHODS: Male Sprague-Dawley rats were given a high-fat diet for 10 weeks. The rats were administered tiopronin (20 mg/kg) or a positive control drug ursodeoxycholic acid (UDCA, 15 mg/kg) via gavage daily from week 5 to week 10. After the rats were sacrificed, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), free fatty acids (FFA), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C), and liver homogenate FFA, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were measured using commercial analysis kits. The expression levels of CYP2E1 mRNA and protein were determined using RT-PCR and immunoblot assays, respectively. RESULTS: Tiopronin significantly lowered both the serum ALT and AST levels, while only the serum ALT level was lowered by UDCA. Tiopronin significantly decreased the serum and liver levels of TG, TC and FFA as well as the serum LDL-C level, and increased the serum HDL-C level, while UDCA decreased the serum and liver TC levels as well as the serum LDL-C level, but did not change the serum levels of TG, FFA and HDL-C. Tiopronin apparently ameliorated the hepatocyte degeneration and the infiltration of inflammatory cells in the livers, but UDCA did not affect the pathological features of the livers. Both tiopronin and UDCA ameliorated the mitochondrial abnormality in the livers. The benefits of tiopronin were associated with increased SOD and GSH-Px activities, and with decreased MDA activity and CYP2E1 expression in the livers. CONCLUSION: Tiopronin exerts protective effects against non-alcoholic steatohepatitis in rats, which may be associated with its antioxidant properties and regulation of lipid metabolism. SN - 1745-7254 UR - https://www.unboundmedicine.com/medline/citation/22543705/Protective_effects_of_tiopronin_against_high_fat_diet_induced_non_alcoholic_steatohepatitis_in_rats_ L2 - https://doi.org/10.1038/aps.2012.19 DB - PRIME DP - Unbound Medicine ER -