Author/Authors :
niknahad، hossein نويسنده , , Heidari، Reza نويسنده Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. , , Firuzi، Roya نويسنده Pharmacology and Toxicology Department, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran. , , Abazari، Farzaneh نويسنده Pharmacology and Toxicology Department, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran. , , Ramezani، Maral نويسنده Pharmacology and Toxicology Department, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran. , , Azarpira، Negar نويسنده , , Hosseinzadeh، Massood نويسنده Department of Pathology, Shiraz University of Medical Sciences, Shiraz, Iran Hosseinzadeh, Massood , Najibi، Asma نويسنده Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran , , Saeedi، Arastoo نويسنده Pharmacology and Toxicology Department, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran. ,
Abstract :
Purpose: Accumulating evidence suggests that drug exposure during a modest inflammation induced by bacterial lipopolysaccharide (LPS) might increase the risk of drug-induced liver injury. The current investigation was designed to test if antimalarial drugs hepatotoxicity is augmented in LPS‑treated animals.
Methods: Rats were pre-treated with LPS (100 µg/kg, i.p). Afterward, non-hepatotoxic doses of amodiaquine (25, 50 and 100 mg/kg, oral) and chloroquine (25, 50 and 100 mg/kg, oral) were administered.
Results: Interestingly, liver injury was evident only in animals treated with both drug and LPS as estimated by pathological changes in serum biochemistry (ALT, AST, LDH, and TNF-α), and liver tissue (severe hepatitis, endotheliitis, and sinusoidal congestion). An increase in liver myeloperoxidase enzyme activity, lipid peroxidation, and protein carbonylation, along with tissue glutathione depletion were also detected in LPS and drug co-treated animals.
Conclusion: Antimalarial drugs rendered hepatotoxic in animals undergoing a modest inflammation. These results indicate a synergistic liver injury from co-exposure to antimalarial drugs and inflammation.
