Background China is one of the high burden countries of Mycobacterium tuberculosis （TB） infection globally, with high incidence and mortality. We studied the molecular characteristics of rifampin （RIF） and isoniaz...Background China is one of the high burden countries of Mycobacterium tuberculosis （TB） infection globally, with high incidence and mortality. We studied the molecular characteristics of rifampin （RIF） and isoniazid （INH） resistant Mycobacterium tuberculosis strains from Beijing, China, in order to find out the genetic marker for rapid detection of specific drug resistance.Methods Forty pansusceptible and 81 resistant strains of Mycobacterium tuberculosis isolated from Beijing, China during 2002-2005 were analyzed. The modified rifampin oligonucleotide （RIFO） assay based on reverse line blot hybridization was used to detect mutations in the 81 bp hot-spot region of rpoB gene, which is associated with RIF resistance. The INH resistance associated genes, regulatory region mab-inhA （-15C/T） and structural gene katG S315T were detected by reverse line blot hybridization and PCR-restriction fragment length polymorphism （RFLP） method respectively. All the strains were typed by spoligotying and the Beijing genotype was further subdivided by NTF locus analysis. The distribution of drug resistance associated mutations in the above genes was compared in these groups. Results Sixty-five （91.5%） of 71 RIF resistant and 52 （92.9%） of 56 multidrug-resistant （MDR, i.e. resistant to at least RIF and INH） strains were found to harbor mutations in the rpoB hot-spot region. No mutation was detected in RIF sensitive strains. The specificity and sensitivity of the modified RIFO assay were 100% and 91.5%, respectively, katG315 AGC〉ACC and inhA-15C〉T mutations were found in 40 （60.6%） and 10 （15.2%） of 66 INH resistant strains, respectively; 7.6% of INH-resistant strains had mutations in both of these genes. Therefore, a combined use of both katG315 and inhA-15 identified 68.2% of INH-resistant strains. The Beijing genotype accounted for 91.7% of total strains and was further subdivided into ＂modern＂ （76.6%） and ＂ancestral＂ （23.4%） group. There is no significant difference展开更多
Drug-induced liver injury is the common adverse effect seen in patients receiving antituberculosis drugs （ATDs）. There are several risk factors associated with the development of hepatotoxicity in such patients. Tho...Drug-induced liver injury is the common adverse effect seen in patients receiving antituberculosis drugs （ATDs）. There are several risk factors associated with the development of hepatotoxicity in such patients. Though there have been appreciable efforts taken by carrying out studies investigating the efficacy of several natural and synthetic compounds in minimising this effect, the only choice available for clinicians is withdrawal of drugs. This review would give a precise idea of ATD-induced hepatotoxicity its underlying mechanisms and alternative therapies for the same.展开更多
Isoniazid(INH) is highly effective for the management of tuberculosis.However,it can cause liver injury and even liver failure.INH metabolism has been thought to be associated with INH-induced liver injury.This review...Isoniazid(INH) is highly effective for the management of tuberculosis.However,it can cause liver injury and even liver failure.INH metabolism has been thought to be associated with INH-induced liver injury.This review summarized the metabolic pathways of INH and discussed their associations with INH-induced liver injury.展开更多
AIM： To evaluate the hepatoprotective effect of garlic on liver injury induced by isoniazid （INH） and rifarnpicin （RIF）. METHODS： Wistar rats weighing 150-200 g were treated orally with 50 mg/kg of INH and RIF d...AIM： To evaluate the hepatoprotective effect of garlic on liver injury induced by isoniazid （INH） and rifarnpicin （RIF）. METHODS： Wistar rats weighing 150-200 g were treated orally with 50 mg/kg of INH and RIF daily each for 28 d. For hepatoprotective studies, 0.25 g/kg per day of freshly prepared garlic hornogenate was administered orally half an hour before the INH＋RIF doses. Serum alanine arninotransferase （AIT）, aspartate aminotransferase （AST） and bilirubin were estimated on d 0, 14, 21, and 28 in all the rats. Histological analysis was carried out to assess the injury to the liver. Lipid peroxidation （1PO） as a marker of oxidative stress and non-protein thiols （glutathione） for antioxidant levels were measured in liver hornogenate. RESULTS： The treatment of rats with INH＋RIF （50 mg/kg per day each） induced hepatotoxicity in all the treated animals as judged by elevated serum ALT, AST, and bilirubin levels, presence of focal hepatocytic necrosis （6/8） and portal triaditis （8/8）. Garlic simultaneously administered at a dose of 0.25 g/kg per day prevented the induction of histopathological injuries in INH＋RIF co-treated animals, except in 4 animals, which showed only moderate portal triaditis. The histological changes correlated with oxidative stress in INH＋RIF treated animals. The group which received 0.25 g/kg per day garlic hornogenate along with INH＋RIF showed higher levels of glutathione （P〈0.05） and low levels of 1PO （P〈 0.05） as compared to INH＋RIF treated group. CONCLUSION： Freshly prepared garlic homogenate protects against INH＋RIF-induced liver injury in experimental animal model.展开更多
基金This study was supported by a grant from the National Natural Science Foundation of China(No.30471841).
文摘Background China is one of the high burden countries of Mycobacterium tuberculosis （TB） infection globally, with high incidence and mortality. We studied the molecular characteristics of rifampin （RIF） and isoniazid （INH） resistant Mycobacterium tuberculosis strains from Beijing, China, in order to find out the genetic marker for rapid detection of specific drug resistance.Methods Forty pansusceptible and 81 resistant strains of Mycobacterium tuberculosis isolated from Beijing, China during 2002-2005 were analyzed. The modified rifampin oligonucleotide （RIFO） assay based on reverse line blot hybridization was used to detect mutations in the 81 bp hot-spot region of rpoB gene, which is associated with RIF resistance. The INH resistance associated genes, regulatory region mab-inhA （-15C/T） and structural gene katG S315T were detected by reverse line blot hybridization and PCR-restriction fragment length polymorphism （RFLP） method respectively. All the strains were typed by spoligotying and the Beijing genotype was further subdivided by NTF locus analysis. The distribution of drug resistance associated mutations in the above genes was compared in these groups. Results Sixty-five （91.5%） of 71 RIF resistant and 52 （92.9%） of 56 multidrug-resistant （MDR, i.e. resistant to at least RIF and INH） strains were found to harbor mutations in the rpoB hot-spot region. No mutation was detected in RIF sensitive strains. The specificity and sensitivity of the modified RIFO assay were 100% and 91.5%, respectively, katG315 AGC〉ACC and inhA-15C〉T mutations were found in 40 （60.6%） and 10 （15.2%） of 66 INH resistant strains, respectively; 7.6% of INH-resistant strains had mutations in both of these genes. Therefore, a combined use of both katG315 and inhA-15 identified 68.2% of INH-resistant strains. The Beijing genotype accounted for 91.7% of total strains and was further subdivided into ＂modern＂ （76.6%） and ＂ancestral＂ （23.4%） group. There is no significant difference
文摘Drug-induced liver injury is the common adverse effect seen in patients receiving antituberculosis drugs （ATDs）. There are several risk factors associated with the development of hepatotoxicity in such patients. Though there have been appreciable efforts taken by carrying out studies investigating the efficacy of several natural and synthetic compounds in minimising this effect, the only choice available for clinicians is withdrawal of drugs. This review would give a precise idea of ATD-induced hepatotoxicity its underlying mechanisms and alternative therapies for the same.
基金supported in part by the U.S. National Institute of Diabetes and Digestive and Kidney Diseases (DK090305) for Xiaochao Mathe National Institute of General Medical Sciences (GM087376 and GM118367) for Xiao-bo Zhong
文摘Isoniazid(INH) is highly effective for the management of tuberculosis.However,it can cause liver injury and even liver failure.INH metabolism has been thought to be associated with INH-induced liver injury.This review summarized the metabolic pathways of INH and discussed their associations with INH-induced liver injury.
基金Supported by the Indian Council of Medical Research,New Delhi,India,No.45/39/2002-PHA/BMS
文摘AIM： To evaluate the hepatoprotective effect of garlic on liver injury induced by isoniazid （INH） and rifarnpicin （RIF）. METHODS： Wistar rats weighing 150-200 g were treated orally with 50 mg/kg of INH and RIF daily each for 28 d. For hepatoprotective studies, 0.25 g/kg per day of freshly prepared garlic hornogenate was administered orally half an hour before the INH＋RIF doses. Serum alanine arninotransferase （AIT）, aspartate aminotransferase （AST） and bilirubin were estimated on d 0, 14, 21, and 28 in all the rats. Histological analysis was carried out to assess the injury to the liver. Lipid peroxidation （1PO） as a marker of oxidative stress and non-protein thiols （glutathione） for antioxidant levels were measured in liver hornogenate. RESULTS： The treatment of rats with INH＋RIF （50 mg/kg per day each） induced hepatotoxicity in all the treated animals as judged by elevated serum ALT, AST, and bilirubin levels, presence of focal hepatocytic necrosis （6/8） and portal triaditis （8/8）. Garlic simultaneously administered at a dose of 0.25 g/kg per day prevented the induction of histopathological injuries in INH＋RIF co-treated animals, except in 4 animals, which showed only moderate portal triaditis. The histological changes correlated with oxidative stress in INH＋RIF treated animals. The group which received 0.25 g/kg per day garlic hornogenate along with INH＋RIF showed higher levels of glutathione （P〈0.05） and low levels of 1PO （P〈 0.05） as compared to INH＋RIF treated group. CONCLUSION： Freshly prepared garlic homogenate protects against INH＋RIF-induced liver injury in experimental animal model.
