The traditional Chinese medicine（Tripterygium wilfordii Hook.f., TWH） has been clinically used to treat primary and secondary renal diseases and proteinuria for nearly 40 years. However, there is a rare literature a...The traditional Chinese medicine（Tripterygium wilfordii Hook.f., TWH） has been clinically used to treat primary and secondary renal diseases and proteinuria for nearly 40 years. However, there is a rare literature about the effect of triptolide（the main active ingredient of TWH） on the expression of oxidative carbonyl protein（OCP） in diabetic nephropathy（DN）. This study aimed to provide experimental evidence for triptolide treatment on DN through its effect on the expression of OCP, in order to investigate the effects of triptolide on the expression of OCP in rats with DN. Sixty SD rats were randomly divided into five groups： control group, high-dose triptolide（Th） group, low-dose triptolide（Tl） group, DN model group, and positive control（benazepril） group. The DN model was established using streptozotocin. Urinary protein excretion, fasting blood glucose（FBG）, superoxide dismutase（SOD） in renal homogenate, malondialdehyde（MDA） in renal homogenate and renal nitrotyrosine by immunohistochemistry, and the expression of OCP by oxyblotimmune blotting were detected. In the DN model group, rat urinary protein excretion and renal MDA were significantly increased, while renal SOD significantly decreased and nitrotyrosine expression was obviously upregulated in the kidney. After triptolide treatment, 24-h urinary protein excretion（61.96±19.00 vs. 18.32±4.78 mg/day, P〈0.001）, renal MDA（8.09±0.79 vs. 5.45±0.68 nmol/L, P〈0.001）, and nitrotyrosine expression were decreased. Furthermore, renal OCP significantly decreased, while renal SOD（82.50±19.10 vs. 124.00±20.52 U/L, P〈0.001） was elevated. This study revealed that triptolide can down-regulate the expression of OCP in the renal cortex of DN rats.展开更多
Background Modern research has provided new insights into the biological mechanisms of noise-induced hearing loss, and a number of studies showed the appearance of increased reactive oxygen species （ROS） and reactiv...Background Modern research has provided new insights into the biological mechanisms of noise-induced hearing loss, and a number of studies showed the appearance of increased reactive oxygen species （ROS） and reactive nitrogen species （RNS） during and after noise exposure. This study was designed to investigate the noise exposure induced nitrotyrosine change and the mechanism of outer hair cells death in guinea pig cochlea. Method Thirty guinea pigs were used in this study. The experimental animals were either exposed for 4 hours per day to broadband noise at 122 dB SPL （A-weighted） for 2 consecutive days or perfused cochleae with 5 mg/ml of the SIN1 solutions, an exogenous NO and superoxide donor, for 30 minutes. Then the cochleae of the animals were dissected. Propidium iodide （PI）, a DNA intercalating fluorescent probe, was used to trace morphological changes in OHC nuclei. The distribution of nitrotyrosine （NT） in the organ of Corti and the cochlear lateral wall tissue from the guinea pigs were examined using fluorescence immunohistochemistry method. Whole mounts of organ of Corti were prepared. Morphological and fluorescent changes were examined under a confocal microscope. Results Either after noise exposure or after SIN1 perfusion, outer hair cells （OHCs） death with characteristics of both apoptotic and necrotic degradation appeared. Nitrotyrosine immunolabeling could be observed in the OHCs from the control animals. After noise exposure, NT immunostaining became much greater than the control animals in OHCs. The apoptotic OHC has significant increase of nitrotyrosine in and around the nucleus following noise exposure. In the normal later wall of cochleae, relatively weak nitrotyrosine immunolabeling could be observed. After noise exposure, nitrotyrosine immunoactivity became stronger in stria vascularis. Conclusion Noise exposure induced increase of nitrotyrosine production is associated with OHCs death suggesting reactive nitrogen species participation in the cochlear pathophysiolo展开更多
Diabetic nephropathy（DN） is a common and serious clinical complication of diabetes and presently there are no effective ways to prevent its occurrence and progression. Recent studies show that pentoxifylline（PTX） ...Diabetic nephropathy（DN） is a common and serious clinical complication of diabetes and presently there are no effective ways to prevent its occurrence and progression. Recent studies show that pentoxifylline（PTX） can improve renal hemodynamics, reduce urinary protein excretion, and alleviate or delay renal failure in DN patients. In this study, we focused on the anti-oxidative stress effect of PTX on alleviating renal damages of DN using rat models. DN rats were established with injection of streptozotocin. Blood glucose, urinary protein excretion, serum cystatin C, renal biopsy, superoxide dismutase（SOD） and malondialdehyde（MDA） in serum and renal homogenate and renal nitrotyrosine levels were analyzed before and 12 weeks after the treatment of PTX. Before treatment, all the DN rats had elevated blood glucose, increased urinary protein excretion and elevated serum cystatin C. Morphologically, DN rats exhibited renal tissue damages, including swelling and fusions of foot processes of podocytes under electron microscope. Masson staining revealed blue collagen deposition in glomeruli and renal interstitium. With treatment of PTX, symptoms and renal pathological changes of DN rats were alleviated. Furthermore, the MDA levels were increased and the SOD levels were decreased in the serum and kidneys of DN rats, and these changes were reversed by PTX. The expression of nitrotyrosine was up-regulated in DN rat model and down-regulated by PTX, indicating that PTX was able to inhibit oxidative reactions in DN rats. PTX could alleviate renal damage in DN, which may be attributable to its anti-oxidative stress activity.展开更多
AIM: To detect the presence of inducible nitric oxide synthase (iNOS), nitrotyrosine (NT) and apoptosis in gastric adenocarcinomas and their possible correlations with the clinicopathological characteristics and progn...AIM: To detect the presence of inducible nitric oxide synthase (iNOS), nitrotyrosine (NT) and apoptosis in gastric adenocarcinomas and their possible correlations with the clinicopathological characteristics and prognosis of gastric adenocarcinoma.METHODS: Sixty-six specimens of gastric adenocarcinoma and corresponding adjacent normal gastric tissues were studied. Immunohistochemistry was employed to localize iNOS and NT protein and an immunohistochemical scoring system was used. The occurrence of apoptotic cell death (apoptotic index [AI]) was analyzed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling (TUNEL) method. RESULTS: Results showed that iNOS expression wasdetected at an intermediate or high level in 41 of 66 (62%) specimens of gastric adenocarcinoma. NT expression was 58%. Neither of them was found in the normal gastric tissues; there were significant positive correlations among iNOSexpression, NT expression and AI. Many clinicopathologic characteristics of gastric adenocarcinoma, such as tumor size, depth of invasion, lymph node metastasis and TNM staging, were related to iNOS and NT expressions (P＜0.05). In 66 surviving patients, the 5-year survival rate of 41 patients who had tumors with intermediate or high iNOS expressions and high Ais (4.09%; 19.96%) was significantly lower than that of 25 patients who had tumors with negative or low iNOS expressions and low Ais (0.79%; 47.14%) (P= 0.001). COX's multivariate analysis revealed that the iNOS expression was identified as one of the significant independent prognostic factors predictive of a poor survival (relative risk [RR] = 2.69).CONCLUSION: NO produced by iNOS may play a stronger role in promoting gastric adenocarcinoma growth than in suppressing its growth. iNOS and NT expressions by gastric adenocarcinoma may correlate with a poor survival.展开更多
AIM:To investigate the effectiveness of antioxidant compounds in modulating mitochondrial oxidative alterations and lipids accumulation in fatty hepatocytes.METHODS:Silybin-phospholipid complex containing vitamin E(Re...AIM:To investigate the effectiveness of antioxidant compounds in modulating mitochondrial oxidative alterations and lipids accumulation in fatty hepatocytes.METHODS:Silybin-phospholipid complex containing vitamin E(Realsil) was daily administered by gavage(one pouch diluted in 3 mL of water and containing 15 mg vitamin E and 47 mg silybin complexed with phospholipids) to rats fed a choline-deprived(CD) or a high fat diet [20% fat,containing 71% total calories as fat,11% as carbohydrate,and 18% as protein,high fat diet(HFD)] for 30 d and 60 d,respectively.The control group was fed a normal semi-purified diet containing adequate levels of choline(35% total calories as fat,47% as carbohydrate,and 18% as protein).Circulating and hepatic redox active and nitrogen regulating molecules(thioredoxin,glutathione,glutathione peroxidase),NO metabolites(nitrosothiols,nitrotyrosine),lipid peroxides [malondialdehyde-thiobarbituric(MDA-TBA)],and pro-inflammatory keratins(K-18) were measured on days 0,7,14,30,and 60.Mitochondrial respiratory chain proteins and the extent of hepatic fatty infiltration were evaluated.RESULTS:Both diet regimens produced liver steatosis(50% and 25% of liver slices with CD and HFD,respectively) with no signs of necro-inflammation:fat infiltration ranged from large droplets at day 14 to disseminated and confluent vacuoles resulting in microvesicular steatosis at day 30(CD) and day 60(HFD).In plasma,thioredoxin and nitrosothiols were not significantly changed,while MDA-TBA,nitrotyrosine(from 6 ± 1 nmol/L to 14 ± 3 nmol/L day 30 CD,P < 0.001,and 12 ± 2 nmol/L day 60 HFD,P < 0.001),and K-18(from 198 ± 20 to 289 ± 21 U/L day 30 CD,P < 0.001,and 242 ± 23 U/L day 60 HFD,P < 0.001) levels increased significantly with ongoing steatosis.In the liver,glutathione was decreased(from 34.0 ± 1.3 to 25.3 ± 1.2 nmol/mg prot day 30 CD,P < 0.001,and 22.4 ± 2.4 nmol/mg prot day 60 HFD,P < 0.001),while thioredoxin and glutathione peroxidase were initially increased and then decreased.Nitrosothiols were constan展开更多
AIM: To compare a possible relation between Helicobacter pylori(H. pylori) and the oxygen- and nitrogen radical system in humans. METHODS: Mechanisms for H. pylori to interfere with the oxygen and nitrogen radical sys...AIM: To compare a possible relation between Helicobacter pylori(H. pylori) and the oxygen- and nitrogen radical system in humans. METHODS: Mechanisms for H. pylori to interfere with the oxygen and nitrogen radical system is of great importance for understanding of the H. pylori persistence and pathogenesis. Biopsies were obtained from the gastric wall of 21 individuals. Ongoing infection with H. pylori was detected using direct analyze from the biopsies using campylobacter-like organism test(CLO-test) and/or by using 14C-urea breath test. The individuals were divided in a negative H. pylori and a positive H. pylori group. Expression in the gastric mucosa of induc-ible nitric oxide syntase(iNOS), nicotinamide adenine dinucleotide phosphate-oxidase(NADPH-oxidase) myeloperoxidase(MPO), and nitrotyrosine were assessed by Western blotting.RESULTS: The individuals who undervent gastroscopy were divided in a H. pylori neg. [n = 13, m/f = 7/6, age(mean) = 39] and a H. pylori pos. group [n = 8, m/f = 5/3, age(mean) = 53]. Using western blot analysis iNOS was detected as a 130 kDa band. The iNOS expression was upregulated in the antrum of H. pylori infected individuals in comparison to the controls, mean ± SD being 12.6 ± 2.4 vs 8.3 ± 3.1, P < 0.01. There was a markedly upregulated expression of MPO in the antrum of H. pylori infected individuals in comparison to the control group without infection. In several of noninfected controls it was not possible to detect any MPO expression at all, whereas the expression was high in all the infected subjects, mean ± SD being 5.1 ± 3.4 vs 2.1 ± 1.9, P < 0.05. The NADPH-oxidase expression was analysed by detecting the NADPH-oxidase subunit p47-phox expression. P47-phox was detected as a 47 kDa band using Western blot, and showed a significantly higher expression of p47-phox in the antrum of the H. pylori infected individuals compared to the controls, mean ± SD being 3.1 ± 2.2 vs 0.3 ± 0.2, P < 0.01. Regarding nitrotyrosine formation, Western blot did not show any significant展开更多
Primary biliary cirrhosis is a multifactor autoimmune disease characterized by hepatic and systemic manifestations,with immune system dysregulation and abnormalities in the hepatic metabolism of bile salts,lipids,and ...Primary biliary cirrhosis is a multifactor autoimmune disease characterized by hepatic and systemic manifestations,with immune system dysregulation and abnormalities in the hepatic metabolism of bile salts,lipids,and nutrients,as well as destruction of membrane lipids and mitochondrial dysfunction.Both oxidative and nitrosative stress are associated with ongoing manifestations of the disease.In particular,abnormalities in nitric oxide metabolism and thiol oxidation already occur at early stages,thus leading to the hypothesis that these biochemical events play a pathogenic role in primary biliary cirrhosis.Moreover,the association of these metabolic abnormalities with the progression of the disease may indicate some biochemical parameters as early diagnostic markers of disease evolution,and may open up the potential for pharmacological intervention to inhibit intra-and extra-cellular stress events for resuming hepatocellular functions.The following paragraphs summarize the current knowledge by outlining molecular mechanisms of the disease related to these stress events.展开更多
基金supported by the program for Outstanding Academic Leaders Training Plan of Health System of Huangpu District of Shanghai from 2013 to 2016 year(No.2013-18)
文摘The traditional Chinese medicine（Tripterygium wilfordii Hook.f., TWH） has been clinically used to treat primary and secondary renal diseases and proteinuria for nearly 40 years. However, there is a rare literature about the effect of triptolide（the main active ingredient of TWH） on the expression of oxidative carbonyl protein（OCP） in diabetic nephropathy（DN）. This study aimed to provide experimental evidence for triptolide treatment on DN through its effect on the expression of OCP, in order to investigate the effects of triptolide on the expression of OCP in rats with DN. Sixty SD rats were randomly divided into five groups： control group, high-dose triptolide（Th） group, low-dose triptolide（Tl） group, DN model group, and positive control（benazepril） group. The DN model was established using streptozotocin. Urinary protein excretion, fasting blood glucose（FBG）, superoxide dismutase（SOD） in renal homogenate, malondialdehyde（MDA） in renal homogenate and renal nitrotyrosine by immunohistochemistry, and the expression of OCP by oxyblotimmune blotting were detected. In the DN model group, rat urinary protein excretion and renal MDA were significantly increased, while renal SOD significantly decreased and nitrotyrosine expression was obviously upregulated in the kidney. After triptolide treatment, 24-h urinary protein excretion（61.96±19.00 vs. 18.32±4.78 mg/day, P〈0.001）, renal MDA（8.09±0.79 vs. 5.45±0.68 nmol/L, P〈0.001）, and nitrotyrosine expression were decreased. Furthermore, renal OCP significantly decreased, while renal SOD（82.50±19.10 vs. 124.00±20.52 U/L, P〈0.001） was elevated. This study revealed that triptolide can down-regulate the expression of OCP in the renal cortex of DN rats.
基金This research was supported by the grants from National Natural Science Foundation of China，Nuttal Alfred's Grant (NIH NIDCD DC 000105 and Shi Xiaorui's Grant
文摘Background Modern research has provided new insights into the biological mechanisms of noise-induced hearing loss, and a number of studies showed the appearance of increased reactive oxygen species （ROS） and reactive nitrogen species （RNS） during and after noise exposure. This study was designed to investigate the noise exposure induced nitrotyrosine change and the mechanism of outer hair cells death in guinea pig cochlea. Method Thirty guinea pigs were used in this study. The experimental animals were either exposed for 4 hours per day to broadband noise at 122 dB SPL （A-weighted） for 2 consecutive days or perfused cochleae with 5 mg/ml of the SIN1 solutions, an exogenous NO and superoxide donor, for 30 minutes. Then the cochleae of the animals were dissected. Propidium iodide （PI）, a DNA intercalating fluorescent probe, was used to trace morphological changes in OHC nuclei. The distribution of nitrotyrosine （NT） in the organ of Corti and the cochlear lateral wall tissue from the guinea pigs were examined using fluorescence immunohistochemistry method. Whole mounts of organ of Corti were prepared. Morphological and fluorescent changes were examined under a confocal microscope. Results Either after noise exposure or after SIN1 perfusion, outer hair cells （OHCs） death with characteristics of both apoptotic and necrotic degradation appeared. Nitrotyrosine immunolabeling could be observed in the OHCs from the control animals. After noise exposure, NT immunostaining became much greater than the control animals in OHCs. The apoptotic OHC has significant increase of nitrotyrosine in and around the nucleus following noise exposure. In the normal later wall of cochleae, relatively weak nitrotyrosine immunolabeling could be observed. After noise exposure, nitrotyrosine immunoactivity became stronger in stria vascularis. Conclusion Noise exposure induced increase of nitrotyrosine production is associated with OHCs death suggesting reactive nitrogen species participation in the cochlear pathophysiolo
基金supported by grants from the Research Program of Huangpu District Science and Technology Committee of Shanghai,China(No.2012-HGG-5)the Program for Outstanding Academic Leaders of Health System of Huangpu District of Shanghai,China(No.2013-18)
文摘Diabetic nephropathy（DN） is a common and serious clinical complication of diabetes and presently there are no effective ways to prevent its occurrence and progression. Recent studies show that pentoxifylline（PTX） can improve renal hemodynamics, reduce urinary protein excretion, and alleviate or delay renal failure in DN patients. In this study, we focused on the anti-oxidative stress effect of PTX on alleviating renal damages of DN using rat models. DN rats were established with injection of streptozotocin. Blood glucose, urinary protein excretion, serum cystatin C, renal biopsy, superoxide dismutase（SOD） and malondialdehyde（MDA） in serum and renal homogenate and renal nitrotyrosine levels were analyzed before and 12 weeks after the treatment of PTX. Before treatment, all the DN rats had elevated blood glucose, increased urinary protein excretion and elevated serum cystatin C. Morphologically, DN rats exhibited renal tissue damages, including swelling and fusions of foot processes of podocytes under electron microscope. Masson staining revealed blue collagen deposition in glomeruli and renal interstitium. With treatment of PTX, symptoms and renal pathological changes of DN rats were alleviated. Furthermore, the MDA levels were increased and the SOD levels were decreased in the serum and kidneys of DN rats, and these changes were reversed by PTX. The expression of nitrotyrosine was up-regulated in DN rat model and down-regulated by PTX, indicating that PTX was able to inhibit oxidative reactions in DN rats. PTX could alleviate renal damage in DN, which may be attributable to its anti-oxidative stress activity.
文摘AIM: To detect the presence of inducible nitric oxide synthase (iNOS), nitrotyrosine (NT) and apoptosis in gastric adenocarcinomas and their possible correlations with the clinicopathological characteristics and prognosis of gastric adenocarcinoma.METHODS: Sixty-six specimens of gastric adenocarcinoma and corresponding adjacent normal gastric tissues were studied. Immunohistochemistry was employed to localize iNOS and NT protein and an immunohistochemical scoring system was used. The occurrence of apoptotic cell death (apoptotic index [AI]) was analyzed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling (TUNEL) method. RESULTS: Results showed that iNOS expression wasdetected at an intermediate or high level in 41 of 66 (62%) specimens of gastric adenocarcinoma. NT expression was 58%. Neither of them was found in the normal gastric tissues; there were significant positive correlations among iNOSexpression, NT expression and AI. Many clinicopathologic characteristics of gastric adenocarcinoma, such as tumor size, depth of invasion, lymph node metastasis and TNM staging, were related to iNOS and NT expressions (P＜0.05). In 66 surviving patients, the 5-year survival rate of 41 patients who had tumors with intermediate or high iNOS expressions and high Ais (4.09%; 19.96%) was significantly lower than that of 25 patients who had tumors with negative or low iNOS expressions and low Ais (0.79%; 47.14%) (P= 0.001). COX's multivariate analysis revealed that the iNOS expression was identified as one of the significant independent prognostic factors predictive of a poor survival (relative risk [RR] = 2.69).CONCLUSION: NO produced by iNOS may play a stronger role in promoting gastric adenocarcinoma growth than in suppressing its growth. iNOS and NT expressions by gastric adenocarcinoma may correlate with a poor survival.
基金Supported by Grants from MIUR(Ministero Università e Ricerca Scientifica COFIN2006)"Fondi Ateneo Ricerca Scientifica 2005/2006" from the University of Bari,Italy
文摘AIM:To investigate the effectiveness of antioxidant compounds in modulating mitochondrial oxidative alterations and lipids accumulation in fatty hepatocytes.METHODS:Silybin-phospholipid complex containing vitamin E(Realsil) was daily administered by gavage(one pouch diluted in 3 mL of water and containing 15 mg vitamin E and 47 mg silybin complexed with phospholipids) to rats fed a choline-deprived(CD) or a high fat diet [20% fat,containing 71% total calories as fat,11% as carbohydrate,and 18% as protein,high fat diet(HFD)] for 30 d and 60 d,respectively.The control group was fed a normal semi-purified diet containing adequate levels of choline(35% total calories as fat,47% as carbohydrate,and 18% as protein).Circulating and hepatic redox active and nitrogen regulating molecules(thioredoxin,glutathione,glutathione peroxidase),NO metabolites(nitrosothiols,nitrotyrosine),lipid peroxides [malondialdehyde-thiobarbituric(MDA-TBA)],and pro-inflammatory keratins(K-18) were measured on days 0,7,14,30,and 60.Mitochondrial respiratory chain proteins and the extent of hepatic fatty infiltration were evaluated.RESULTS:Both diet regimens produced liver steatosis(50% and 25% of liver slices with CD and HFD,respectively) with no signs of necro-inflammation:fat infiltration ranged from large droplets at day 14 to disseminated and confluent vacuoles resulting in microvesicular steatosis at day 30(CD) and day 60(HFD).In plasma,thioredoxin and nitrosothiols were not significantly changed,while MDA-TBA,nitrotyrosine(from 6 ± 1 nmol/L to 14 ± 3 nmol/L day 30 CD,P < 0.001,and 12 ± 2 nmol/L day 60 HFD,P < 0.001),and K-18(from 198 ± 20 to 289 ± 21 U/L day 30 CD,P < 0.001,and 242 ± 23 U/L day 60 HFD,P < 0.001) levels increased significantly with ongoing steatosis.In the liver,glutathione was decreased(from 34.0 ± 1.3 to 25.3 ± 1.2 nmol/mg prot day 30 CD,P < 0.001,and 22.4 ± 2.4 nmol/mg prot day 60 HFD,P < 0.001),while thioredoxin and glutathione peroxidase were initially increased and then decreased.Nitrosothiols were constan
基金Supported by The grants financially from the Swedish Medical Research Council and the Gothenburg Medical Society
文摘AIM: To compare a possible relation between Helicobacter pylori(H. pylori) and the oxygen- and nitrogen radical system in humans. METHODS: Mechanisms for H. pylori to interfere with the oxygen and nitrogen radical system is of great importance for understanding of the H. pylori persistence and pathogenesis. Biopsies were obtained from the gastric wall of 21 individuals. Ongoing infection with H. pylori was detected using direct analyze from the biopsies using campylobacter-like organism test(CLO-test) and/or by using 14C-urea breath test. The individuals were divided in a negative H. pylori and a positive H. pylori group. Expression in the gastric mucosa of induc-ible nitric oxide syntase(iNOS), nicotinamide adenine dinucleotide phosphate-oxidase(NADPH-oxidase) myeloperoxidase(MPO), and nitrotyrosine were assessed by Western blotting.RESULTS: The individuals who undervent gastroscopy were divided in a H. pylori neg. [n = 13, m/f = 7/6, age(mean) = 39] and a H. pylori pos. group [n = 8, m/f = 5/3, age(mean) = 53]. Using western blot analysis iNOS was detected as a 130 kDa band. The iNOS expression was upregulated in the antrum of H. pylori infected individuals in comparison to the controls, mean ± SD being 12.6 ± 2.4 vs 8.3 ± 3.1, P < 0.01. There was a markedly upregulated expression of MPO in the antrum of H. pylori infected individuals in comparison to the control group without infection. In several of noninfected controls it was not possible to detect any MPO expression at all, whereas the expression was high in all the infected subjects, mean ± SD being 5.1 ± 3.4 vs 2.1 ± 1.9, P < 0.05. The NADPH-oxidase expression was analysed by detecting the NADPH-oxidase subunit p47-phox expression. P47-phox was detected as a 47 kDa band using Western blot, and showed a significantly higher expression of p47-phox in the antrum of the H. pylori infected individuals compared to the controls, mean ± SD being 3.1 ± 2.2 vs 0.3 ± 0.2, P < 0.01. Regarding nitrotyrosine formation, Western blot did not show any significant
文摘Primary biliary cirrhosis is a multifactor autoimmune disease characterized by hepatic and systemic manifestations,with immune system dysregulation and abnormalities in the hepatic metabolism of bile salts,lipids,and nutrients,as well as destruction of membrane lipids and mitochondrial dysfunction.Both oxidative and nitrosative stress are associated with ongoing manifestations of the disease.In particular,abnormalities in nitric oxide metabolism and thiol oxidation already occur at early stages,thus leading to the hypothesis that these biochemical events play a pathogenic role in primary biliary cirrhosis.Moreover,the association of these metabolic abnormalities with the progression of the disease may indicate some biochemical parameters as early diagnostic markers of disease evolution,and may open up the potential for pharmacological intervention to inhibit intra-and extra-cellular stress events for resuming hepatocellular functions.The following paragraphs summarize the current knowledge by outlining molecular mechanisms of the disease related to these stress events.
