Pharm Sci. 2018;24(4): 257-263.
doi: 10.15171/PS.2018.38

Scopus ID: 85059598073
  Abstract View: 3202
  PDF Download: 2319

Research Article

Cytoprotective Properties of Carnosine against Isoniazid-Induced Toxicity in Primary Cultured Rat Hepatocytes

Aziz Eftekhari 1, Reza Heidari 2, Elham Ahmadian 3,4* ORCID logo, Mohammad Ali Eghbal 5*

1 Pharmacology and Toxicology Department, Maragheh University of Medical Sciences, Maragheh, Iran.
2 Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
3 Dental and Periodontal Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
4 Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
5 Pharmacology and Toxicology Department, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.


Background: Drug-induced liver injury is a critical clinical complication. Hence, finding new and safe protective agents with potential clinical application is of value. Isoniazid (INH) is an antituberculosis agent widely used against Mycobacterium tuberculosis infection in human. On the other hand, hepatotoxicity is a clinical complication associated with isoniazid therapy. Oxidative stress and its associated events are major mechanisms identified for INH-induced liver injury. Carnosine is an endogenously found peptide widely investigated for its hepatoprotective effects. On the other hand, robust antioxidant and cytoprotective effects have been attributed to this peptide. Methods: The current study designed to evaluate the potential cytoprotective properties of carnosine against INH-induced cytotoxicity in drug-exposed primary cultured rat hepatocytes. Primary cultured rat hepatocytes were incubated with INH (1.2 mM). Results: INH treatment caused significant increase in cell death and lactate dehydrogenase (LDH) release. On the other hand, it was found that markers of oxidative stress including reactive oxygen species were significantly increased in INH-treated cells. Cellular glutathione reservoirs were also depleted in INH-treated group. Carnosine treatment (50 and 100 µM) significantly diminished INH-induced oxidative stress and cytotoxicity. Conclusion: These data mention carnosine as a potential protective agent with therapeutic capability against INH hepatotoxicity.
Keywords: Cytotoxicity, Drug-induced liver injury, Hepatotoxicity, Mitochondria, Oxidative stress, Antioxidants
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Submitted: 01 May 2018
Revision: 25 Jun 2018
Accepted: 26 Jun 2018
ePublished: 30 Dec 2018
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