title: Concurrent Inflammation Augments Antimalarial Drugs-Induced Liver Injury in Rats.
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.
authors.affiliation: Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.; Pharmacology and Toxicology Department, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Niknahad
authors.affiliation: Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Heidari
authors.affiliation: Pharmacology and Toxicology Department, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Roya
authors.initials: R
authors.lastname: Firuzi
authors.affiliation: Pharmacology and Toxicology Department, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Farzaneh
authors.initials: F
authors.lastname: Abazari
authors.affiliation: Pharmacology and Toxicology Department, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Maral
authors.initials: M
authors.lastname: Ramezani
authors.affiliation: Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Negar
authors.initials: N
authors.lastname: Azarpira
authors.affiliation: Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Massood
authors.initials: M
authors.lastname: Hosseinzadeh
authors.affiliation: Pharmacology and Toxicology Department, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Asma
authors.initials: A
authors.lastname: Najibi
authors.affiliation: Pharmacology and Toxicology Department, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Arastoo
authors.initials: A
authors.lastname: Saeedi
keywords: Drug-Induced Liver Injury; Hepatotoxicity; Inflammation; Lipopolysaccharide; Malaria