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.

Il-1 beta [+3953 C/T] and IL-8 [-251 A/T] gene polymorphisms in H.pylori mediated gastric disorders

Previous studies imply that IL-1 and IL-8 gene variations may play a crucial role in the genetic predisposition to different gastric disorders upon H. pylori infection. The aim of this study was to determine the potential association between the prevalence of certain polymorphic sites and the risk of gastric disorders in Iranian population. One hundred and forty three unrelated individuals with different gastric disorders and 374 normal individuals with no gastric disorders and with a negative serology test for H. pylori [control group] were studied for the association between IL-1 beta [+ 3953 C/T] and IL-8 [-251 A/T] gene polymorphisms and H. pylori - mediated gastritis and gastric ulcer. An analysis of genotype frequency for these genes was performed using RFLP- PCR. Based on the data obtained from culture and pathologic findings, the patients were classified into three subpopulations: H pylori [+] non-ulcerative gastritis [+], H. pylori [+] ulcerative gastritis [+] and H. pylori[-] non-ulcerative gastritis [+]. A significantly higher frequency of TT genotype [p=0.02] in IL-1 beta +3953 in H.pylor[+] ulcerative gastritis [+] was revealed compared to the control group. There were no significant differences among other subpopulations. No significant differences in allele and genotype frequencies of IL-8 [-251A/T] were found among the patients. The data suggest that TT genotype in IL- 1 beta +3953 may be a major contributing genetic risk factor for H. pylori induced gastric ulcer. Moreover, the role of other bacterial and host response factors, such as bacterial adherence peptides, host chemokines, and genes involved in gastric acid secretion, must be further investigated in different ethnic populations

effects of some permeability enhancers on the percutaneous absorption of lidocaine

local anesthesia of the intact skin is difficult because of the barrier properties of skin to epicutaneous penetration of local anesthetic drugs. Using local anesthetics with combination of penetration enhancers could overcome this problem. The main objective of this study was to assess the effects of some permeability enhancers on the percutaneous permeation of lidocaine. The effect of polysorbate 80, polysorbate 20, dimethylsulfoxide [DMSO], tert-butyl cyclohexanol [TBCH], and a-terpinol in different concentrations and various ratios of lidocaine to enhancers was evaluated. The results showed that polysorbate 80 and polysorbate 20 has no detectable penetration enhancing effects in guinea pig skin mounted to diffusion cells. The same results were obtained to water/oil] ratio and the type of oil phase [liguid paraffin vs. castor oil]. Addition of DMSO to the previous formulations had a comiderable enhancing effect According to the data, the extent of lidocaine permeation was proportional to me concentration of DMSO in fAese formulations. The best results belonged to the addition of terpenes but interestingly there wasn't any linear relationship between the concentrations of alpha terpinol/ or TBCH and the duration of antinociceptive effects of lidocaine. Based on the results of this study the ratio of 1: 4 from a- terpinol or TBCH to lidocaine results in a better antinociceptive effect and a- terpinol was the best one among of these compounds. This effect was proven with in vivo tail-immersion test to assess the antinociceptive effect of formulations which have shown more penetration

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