Factors affecting drug-induced liver injury: antithyroid drugs as instances

Methimazole and propylthiouracil have been used in the management of hyperthyroidism for more than half a century. However, hepatotoxicity is one of the most deleterious side effects associated with these medications. The mechanism(s) of hepatic injury induced by antithyroid agents is not fully recognized yet. Furthermore, there are no specific tools for predicting the occurrence of hepatotoxicity induced by these drugs. The purpose of this article is to give an overview on possible susceptibility factors in liver injury induced by antithyroid agents. Age, gender, metabolism characteristics, alcohol consumption, underlying diseases, immunologic mechanisms, and drug interactions are involved in enhancing antithyroid drugs-induced hepatic damage. An outline on the clinically used treatments for antithyroid drugs-induced hepatotoxicity and the potential therapeutic strategies found to be effective against this complication are also discussed.

Effect of lycopene on cyclophosphamide-induced hemorrhagic cystitis in rats

Cylophosphamide is used alone or in combination with other drugs for treatment of neoplastic diseases. Hemorrhagic cystitis is a major potential toxicity and dose limiting side effect of cyclophosphamide. The aim of this study was to evaluate the effects of lycopene compared with some antioxidants for the prevention of cyclophosphamide induced hemorrhagic cystitis in rats. In this study, male Sparague-Dawley rats divided into 17 groups of six animals. Group 1 received saline [10 ml/kg, i.p] as normal control, group 2 received cyclophosphamide [200 mg/kg, i.p] as a single dose, groups 3-10 received Mesna [40 mg/kg, i.p], N-acetylcysteine [100 mg/kg i.p], dithiotheritol [50 mg/kg, i.p], L-carnitine [200 and 400 mg/kg, i.p], grape seed extract [500 mg/kg i.p] and lycopene [0.1 and 0.5 mg/kg, i.p] alone. Groups 11-17 received Mesna [40 mg/kg, i.p], N-acetylcysteine [100 mg/kg, i.p], dithiotheritol [50 mg/kg, i.p], L-carnitine [400 mg/kg, i.p], grape seed extract [500 mg/kg, i.p] and lycopene [0.1 and 0.5 mg/kg, i.p], 5 minutes before, and 2 and 6 hours after administration of 200 mg/kg cyclophosphamide. Pathological and biochemical analysis was evaluated 24 hours after cyclophosphamide administration Mesna and N-acetylcysteine resulted in some but not full protection against cyclophosphamide toxicity compared to the controls. Lycopene [0.1 and 0.5 mg/kg] was efficient in protecting the bladder from cyclophosphamide induced hemorrhagic cystitis. However, dithiotheritol, L- carnitine and grape seed extract did not prevent hemorrhagic cystitis. Our results suggest that pre and co- treatment of lycopene [0.1 and 0.5 mg/kg] with cyclophosphamide may have therapeutic potential to inhibit the hemorrhagic cystitis by cyclophosphamide

Synthesis and smooth muscle calcium channel antagonist effects of new derivatives of 1, 4 - dihydropyridine containing nitroimidazolyl substituent

A group of racemic 3-[[2-hydroxyethyl], [2-Methoxyethyl], [2-acetylethyl] or [2-cyanoethyl]], 5- methyl, ethyl or isopropyl-1, 4-dihydro-2, 6-dimethyl-4-[1-methyl-5-nitro-2-imidazolyl]-3, 5-pyridinedicarboxylates [XIV-XXV] were prepared by the reaction of 1-methyl-5-nitroimidazol-2-carboxaldehyde [X] with acetoacetic esters [VI-IX] and alkys 3-aminocrotonate [XI-XIII]. In vitro calcium channel antagonist activities of the tested compounds were determined by their effects on contraction of Guinea Pig Ileal Longitudinal Smooth Muscle [GPILSM] which was induced by carbacol [1.67