96th-hour impact of scalding burns on end organ damage, systemic oxidative stress, and wound healing in rats treated with three different types of dressings.

In this study, we investigated the effects of three different burn dressing treatments, including experimental, silver, and modern dressing materials, on systemic oxidative stress in rats with severe scald burns within the first 96 h. The rats were divided into five groups: a burn group (n = 10), a polylactic membrane (PLM) group (n = 10), a silver sulfadiazine (SSD) group (n = 10), a curcumin group (n = 10), and a control group (n = 10), consisting of equal numbers of female and male rats. In the first four groups, 30% of the rats' total body surface area was scalded at 95°C. The burn group was not treated. Each group was treated with group-name dressing material. The control group was neither treated nor burned. The rats were sacrificed, and blood and tissue samples were obtained at the 96th hour when severe effects of oxidative stress developed postburns. Systemic inflammatory biomarkers and oxidative stress parameters were examined. In addition, apoptosis and organ damage in liver, kidney, lung, and skin tissues were evaluated biochemically and histopathologically. When the parameters were statistically analyzed, we found that systemic levels of oxidative stress and inflammatory damage to liver, kidney, and lung tissues were lower in the three treated groups than in the burn group. We believe that the dressing material's efficacy in the treatment of severe burns may be dependent on its ability to combat oxidative stress and inflammation.

Histopathological and ultra-structural investigation of the damaging effects of hypoinsulinemia, hyper glycaemia and oxidative stress caused by parenteral nutrition combined with fasting on the small intestine of rabbits.

BACKGROUND AND STUDY AIMS: Parenteral nutrition (PN) is a life-saving practice when the use of the gastrointestinal tract is not appropriate. Despite its great benefits, however, PN may cause several complications. In this study, we conducted histopathological and ultra-structural examinations of the effect of PN combined with starvation on the small intestines of rabbits. MATERIALS AND METHODS: Rabbits were divided into four groups. A fasting + PN group was left completely unfed and received all its daily required energy by PN through an intravenous central catheter. An oral feeding + PN group received half the necessary daily calories by oral feeding and the other half through PN. A semi-starvation group received only half the necessary daily calories by oral feeding and no PN. The fourth group, serving as a control, was supplied with its entire daily energy requirements through oral feeding. After 10 days, the rabbits were euthanized. Blood and small intestine tissue samples were collected from all groups. Blood samples were biochemically analysed, and tissue samples were examined by light and transmission electron microscopy. RESULTS: The fasting + PN group exhibited lower insulin levels, higher glucose levels, and increased systemic oxidative stress than the other groups. Ultra-structural and histopathological examinations revealed a significant increase in apoptotic activity in this group's small intestines and a significant decrease in villus length and crypt depth. Severe damage to the intracellular organelles and nuclei of enterocytes was also observed. CONCLUSION: PN combined with starvation appears to cause apoptosis in the small intestine due to oxidative stress and hyperglycaemia with hypoinsulinemia, with destructive effects on small intestine tissue. Adding enteral nutrition to PN may reduce these destructive effects.

Investigation of Serum Interleukin 6, High-Sensitivity C-Reactive Protein and White Blood Cell Levels during the Diagnosis and Treatment of Paediatric Appendicitis Patients Before and during the COVID-19 Pandemic.

Introduction: In this study, we prospectively investigated changes in serum interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP) and full white blood cell (WBC) counts during the diagnosis and treatment of paediatric patients with appendicitis. We also investigated the effects of the COVID-19 pandemic on the diagnosis and treatment processes of paediatric appendicitis patients. Materials and Methods: A non-perforated appendicitis group (n = 110), a perforated appendicitis group (n = 35) and an appendicitis + COVID-19 group (n = 8) were formed. Blood samples were taken upon admission and every day until the three studied parameters returned to normal values. To investigate the effects of the COVID-19 pandemic on paediatric appendicitis patients, the perforated appendicitis rates and the times from the onset of the first symptoms to the operation before and during the pandemic were compared. Results: WBC, IL-6, and hsCRP dropped below the upper limits on the second postoperative day in the non-perforated appendicitis group, four to six days postoperatively in the perforated appendicitis group, and three to six days postoperatively in the appendicitis + COVID-19 group. These parameters were not within normal range in patients who developed complications during follow-up. The time from the onset of abdominal pain to the surgery was significantly longer during than before the pandemic in both the non-perforated appendicitis group and the perforated appendicitis group. Conclusions: Our results show that WBC, IL-6, and hsCRP are useful laboratory parameters that can complete clinical examinations in the diagnosis of appendicitis in paediatric patients and the identification of complications that may develop postoperatively.

Impact of COVID-19 pandemic on pediatric appendicitis hospital admission time and length of hospital stay.

BACKGROUND: Appendicitis is one of the most common surgical emergencies among children. In this retrospective clinical study, we attempted to determine the effects of the COVID-19 pandemic period on hospital admission time and length of hospital stay (LOS) in pediatric appendicitis cases. METHODS: We retrospectively compared pediatric appendectomies from the date of the first reported COVID-19 case to June 1, 2020, which is considered as the start of the normalization process, with pre-pandemic pediatric appendectomies of the same number of days in terms of age, gender, hospital admission time, LOS, parental educational level, laboratory values, and histopathological findings. RESULTS: There was an average increase of 2 days in the time from the onset of symptoms to hospital admission in pediatric appen-dicitis patients in the COVID-19 period (p=0.001). Furthermore, C-reactive protein value was statistically significantly higher in the COVID-19 period (p=0.018). Given the LOS, it was calculated as an average of 5 days in the pre-pandemic period and 4 days in the COVID-19 period, and this difference was statistically insignificant (p=0.273). There was no significant difference between the groups in terms of histopathological findings (p=0.176). The parental educational level had no effect on the admission time. CONCLUSION: The hospital admission time of pediatric appendicitis patients is significantly prolonged in the COVID-19 pandemic, but this prolongation had no histopathological effect. During the pandemic, the recovery of patients who required urgent treatment during the 'stay-at-home' period was also negatively affected. Notwithstanding, we are of the opinion that the absence of an increase in the LOS may be due to the willingness of both families and physicians to keep the LOS as short as possible. Despite the increase in hospital admission time in pediatric appendicitis during the Covid 19 pandemic process, the lack of increase in the rate of complicated appendicitis may be an indicator of the importance of other factors in the development of complicated appendicitis.

Ultra-structural and histopathological features of liver biopsy taken during laparotomy to confirm the diagnosis of biliary atresia.

Background: Neonatal cholestasis is caused by a group of diseases that cause jaundice, which can be encountered in the neonatal period. Biliary atresia (BA) and idiopathic neonatal hepatitis (INH) are among neonatal cholestasis diseases. Aims: The aim of this study was to perform histopathological and ultra-structural examinations of liver biopsy tissue samples from BA and INH patients with liver biopsies taken during laparotomy to confirm the diagnosis of biliary atresia. Settings and Design: A total of patients undergoing Kasai surgery before the age of 60 days were included in an "early" group (n = 7), whereas patients undergoing surgery after the age of 60 days were included in a "late" group (n = 11). The control group (n = 11) included INH patients. Materials and Methods: For histopathological examinations, liver tissue samples obtained intra-operatively were subjected to routine histopathological procedures after being stained with caspase-3 and cytokeratin-7 antibodies. Ultra-structural evaluations were also performed. Statistical analysis used: For comparisons between the groups, a one-way analysis of variance (ANOVA) test and the Mann-Whitney U test were used for continuous variables. Results: Histopathological findings reflected the specific liver pathologic findings seen in biliary atresia. Although there was no significant difference between the BA groups, these parameters were not detected in the control group. The histopathological evaluations revealed no significant differences in the findings of liver parenchyma damage between the early, late, and control groups. Electron microscopic examinations showed that the patients in the late group had more severe signs of intra-cellular damage to the liver. Conclusions: Although the histopathological examination revealed no significant differences in liver damage between the three groups, in ultra-structural evaluation, intra-cellular damage was found to be less in groups with better prognosis. Electron microscopy evaluations of intra-cellular damage may be more useful in this respect.

Global gene expression profiling in congenital diaphragmatic hernia (CDH) patients.

Congenital diaphragmatic hernia (CDH) is an anomaly characterized by a defect in the diaphragm, leading to the passage of intra-abdominal organs into the thoracic cavity. Herein, the presented work analyzes the global gene expression profiles in nine CDH and one healthy newborn. All of the patients had left posterolateral (Bochdalek) diaphragmatic hernia, operated via an abdominal approach, and stomach and bowels in the thorax cavity. Some patients also had additional anomalies. A total of 560 differentially regulated genes were measured. Among them, 11 genes showed significant changes in expression associated with lung tissue, vascular structure development, and vitamin A metabolism, which are typical ontologies related to CDH etiology. Among them, SLC25A24 and RAB3IL1 are involved in angiogenesis, HIF1A and FOXC2-AS1 are related with the alveolus, MAGI2-AS3 is associated with the diaphragm, LHX4 and DHH are linked with the lung, and BRINP1, FZD9, WNT4, and BLOC1S1-RDH5 are involved in retinol. Besides, the expression levels of some previously claimed genes with CDH etiology also showed diverse expression patterns in different patients. All these indicated that CDH is a complex, multigenic anomaly, requiring holistic approaches for its elucidation.

Glial Cell Line-Derived Neurotrophic Factor, S-100 Protein and Synaptophysin Expression in Biliary Atresia Gallbladder Tissue.

PURPOSE: Biliary atresia (BA) is a disease that manifests as jaundice after birth and leads to progressive destruction of the ductal system in the liver. The aim of this study was to investigate histopathological changes and immunohistochemically examine the expression of glial cell line-derived neurotrophic factor (GDNF), synaptophysin, and S-100 protein in the gallbladder of BA patients. METHODS: The study included a BA group of 29 patients and a control group of 41 children with cholecystectomy. Gallbladder tissue removed during surgery was obtained and examined immunohistochemically and histopathologically. Tissue samples of both groups were immunohistochemically assessed in terms of GDNF, S-100 protein, and synaptophysin expression. Expression was classified as present or absent. Inflammatory activity assessment with hematoxylin and eosin staining and fibrosis assessment with Masson's trichrome staining were performed for tissue sample sections of both groups. RESULTS: Ganglion cells were not present in gallbladder tissue samples of the BA group. Immunohistochemically, GDNF, synaptophysin, and S-100 expression was not detected in the BA group. Histopathological examination revealed more frequent fibrosis and slightly higher inflammatory activity in the BA than in the control group. CONCLUSION: We speculate that GDNF expression will no longer continue in this region, when the damage caused by inflammation of the extrahepatic bile ducts reaches a critical threshold. The study's findings may represent a missing link in the chain of events forming the etiology of BA and may be helpful in its diagnosis.

Impaction of the polylactic membrane or hydrofiber with silver dressings on the interleukin-6, tumor necrosis factor-α, transforming growth factor-b3 levels in the blood and tissues of pediatric patients with burns.

BACKGROUND: We aimed to evaluate the effects of two different burn dressings, hydrofiber with a silver (HFAg) and polylactic membrane (PLM), on altering the levels of important biomarkers Interleukin-6 (IL-6), Tumor necrosis factor-α (TNF-α), Transforming growth factor-ß3 (TGF-ß3) in blood and burnt tissue in children with second-degree burns. METHODS: Children between the ages of one to 16 years, with 25-50% second-degree partial-thickness burns of the total body surface area were included in this study. Patients in the PLM group were dressed with PLM in a typical way according to the manual. The HFAg group was dressed with HFAg and a sterile cover. During and at the end of the 21-day treatment, blood and skin tissue samples were taken from the two burn and control groups. IL-6, TNF-α, and TGF-ß ß3 levels were evaluated in blood and tissue samples from all groups, and the results were analyzed statistically. RESULTS: In the PLM group, IL-6 and TNF-α levels decreased early days in both serum and tissue samples to reach normal ranges compared with the HFAg group. In the PLM group, TGF-ß3 levels were elevated than in other groups for two weeks. CONCLUSION: In this study, we found that PLM controls inflammation earlier in both systemic and burn tissue. We also found that PLM increased the level of TGF-ß3, which may be associated with the prevention of the development of hypertrophic scar in the burn wound, in the blood and burn tissue during this study.

Whole exome sequencing analysis for mutations in isolated type III biliary atresia patients.

AIM OF THE STUDY: Biliary atresia is an idiopathic, destructive disease that affects both extrahepatic and intrahepatic bile ducts with severe inflammation and manifests as progressive jaundice within the first few months of life. In this study, we aimed to investigate the significance of genetic mutations in the onset of biliary atresia disease. MATERIAL AND METHODS: With the approval of the ethics committee and parental consent, blood was taken from patients to obtain their DNA, and the study commenced. In this prospective study, we examined the DNA of 10 patients with no disease other than biliary atresia, and an exome sequence analysis was performed with the new-generation DNA sequencing method. The genetic structure of biliary atresia disease was examined by statistical analysis of the mutations, which were determined according to the reference DNA sequencing. RESULTS: In the exome sequence analysis, the number of mutations detected among the patients changed significantly; the lowest number was 12,591, and the maximum was 19,863. By examining these mutations, we identified the mutated genes that were common to all patients. CONCLUSIONS: In this study, the highest mutation rates were detected in the PRIM2 and MAP2K3 genes. These genes have not previously been associated with biliary atresia.

Investigation of the cardiotoxic effects of parenteral nutrition in rabbits.

INTRODUCTION: Parenteral nutrition (PN) is used for the intravenous delivery of nutrients to patients who cannot take food orally. However, it is not clear whether PN also negatively impacts cardiac tissue. The present empirical study investigated the cardiac effects of PN in rabbits. METHODS: The effects of PN were examined in three groups of rabbits: animals in the PN + fasting group (n = 14) had been fully fasted before receiving a full PN dose via an intravenous central catheter; the PN + oral feeding group (n = 14) received half of the daily calorie requirement as a half dose of PN via an intravenous central catheter; the third group consisted of controls (n = 14) with full enteral feeding and full enteral fluid intake with no PN and no central venous catheter. At the end of the 10-day study period, the rabbits were subjected to echocardiographic examination and euthanized. Blood and tissue samples were obtained from all groups. DNA was isolated from nucleated blood cells. Tissue samples were examined by both light and electron microscopy, relative telomere length was determined from DNA, and blood samples were analyzed biochemically. RESULTS: At the end of the study, there were no statistically significant differences in weight change between the three groups. Echocardiography revealed minimally impaired diastolic function in the PN + fasting group compared to the other groups. Biochemical and histopathological analyses, relative telomere length determination, and electron micrographs showed significant cardiac damage in the PN + fasting group but not in the PN + oral feeding group or the control group. The blood biochemical analyses showed hyperglycemia and a low insulin level in the PN + fasting group but not in the other two groups. CONCLUSIONS: A combination of PN and fasting may damage the cardiac muscle cells of rabbits via a mechanism involving hyperglycemia and oxidative stress. Additional enteral feeding may protect against the destructive effects of PN on cardiac tissue.

Advantages of early intervention with arterial embolization for intra-abdominal solid organ injuries in children.

PURPOSE: Active bleeding due to abdominal trauma is an important cause of mortality in childhood. The aim of this study is to demonstrate the advantages of early percutaneous transcatheter arterial embolization (PTAE) procedures in children with intra-abdominal hemorrhage due to blunt trauma. METHODS: Children with blunt abdominal trauma were retrospectively included. Two groups were identified for inclusion: patients with early embolization (EE group, n=10) and patients with late embolization (LE group, n=11). Both groups were investigated retrospectively and statistically analyzed with regard to lengths of stay in the intensive care unit and in the hospital, first enteral feeding after trauma, blood transfusion requirements, and cost. RESULTS: The duration of stay in the intensive care unit was greater in the LE group than in the EE group (4 days vs. 2 days, respectively). The duration of hospital stay was greater in the LE group than in the EE group (14 days vs. 6 days, respectively). Blood transfusion requirements (15 cc/kg of RBC packs) were greater in the LE group than in the EE group (3 vs. 1, respectively). The total hospital cost was higher in the LE group than in the EE group (4502 USD vs. 1371.5 USD, respectively). The time before starting enteral feeding after first admission was higher in the LE group than in the EE group (4 days vs. 1 day, respectively). CONCLUSION: Early embolization with PTAE results in shorter intensive care and hospitalization stays, earlier enteral feeding, and lower hospital costs for pediatric patients with intra-abdominal hemorrhage due to blunt trauma.

Use of angiographic embolization in trauma-induced pediatric abdominal solid organ injuries.

BACKGROUND: Knowledge of the utility of angiographic embolization (AE) in pediatric cases of blunt abdominal solid organ trauma injuries is limited. The current study is an examination of AE as an effective and reliable method to control bleeding in patients with persistent bleeding due to blunt trauma-induced abdominal solid organ injury. METHODS: This was a retrospective examination of patients <17 years of age who had experienced blunt abdominal solid organ injury and who presented at a single institution within 4 years. A statistical analysis of the data was performed. RESULTS: The mean length of intensive care unit stay was 4 days for those who underwent embolization (n=11), and the mean length of hospital stay was 12 days. The average pre-AE blood loss, as measured by the decrease in hematocrit (%) from admission to embolization, was -7.33+-5.3% (p<0.001). The average post-AE blood loss, as measured by the change in hematocrit 72 hours post AE, was 2+-0.97% (p>0.05). All of the patients were discharged with a full recovery. CONCLUSION: AE was a safe and effective method to control solid organ hemorrhage in pediatric patients with blunt abdominal injuries.

The Effects of Two Different Burn Dressings on Serum Oxidative Stress Indicators in Children with Partial Burn.

In this study, we evaluated and compared the effect of treatment with a hydrofiber dressing with silver (HFAg) and a polylactic membrane (PLM) on systemic oxidative stress in systemic inflammatory reaction in thermal burn injuries in children. A prospective randomized and matched pairing study of 20 to 50% of TBSA was performed from children equal to both sexes affected by thermal injuries. The control group was included in normal children of both sexes. Serum malondialdehyde (MDA), total antioxidant capacity (TAC), total oxidant capacity (TOC), and glutathione (GSH) levels were analyzed and the results were analyzed statistically. In this study, it was found that PLM treatment increased TAC and GSH levels in burn patients significantly more than the other group. With the use of PLM, TOC decreased to normal level from day 3. In the HFAg group, TAC and GSH levels began to increase on the seventh day. On the first day of the burn, the TOC level started to increase. This increase continued on days 7 and 14. The TOC level began to fall on the 21st day. The increase in TAC was higher in the PLM group. In the PLM group, TOC fell faster. As a result, we think that different burn dressings can have different systemic effects. We can speculate that PLM has an antioxidant effect in the burn tissue due to high lactate content. Therefore, PLM may have decreased serum oxidative stress indicators more effectively than HFAg.

The Effects of Different Burn Dressings on Length of Telomere and Expression of Telomerase in Children With Thermal Burns.

BACKGROUND: Burns are a common traumatic injury triggered by local tissue damage and a systemic response. In this study, we evaluated the effects of different burn dressings on telomere kinetics in children with thermal burn injury. METHODS: Sixty children with thermal burn were included in this prospective study. The burn area of the patients included 20 to 50% total body surface area. Three different dressings (hydrofiber with silver [HFAg], poylactic membrane [PLM], and silver sulfadiazine [SSD]) and control groups were created. Telomere length in nucleated blood cells and telomerase expression in the skin tissue were evaluated in control and burn groups. RESULTS: In the whole burn groups, telomere length in blood cells increased. The length of telomeres increased the most in the SSD group. The PLM group is the treatment that increases the number of squamous cell counts in the basal layer and telomerase expression in the skin. In HFAg and SSD groups, the expression of telomerase in the skin is decreased. In the HFAg group, the basal layer in the skin was also reduced in squamous cells. CONCLUSION: In all burn groups, the telomere length of nucleated cells in the blood was higher than in the control group. SSD dressing along with autografting is the treatment method that maximizes telomere length in blood cells. The PLM has the most increased telomerase expression in the skin of burned patients. The PLM application increases the number of cells on both burned and normal skin.

Effects of high-voltage electrical burns and other burns on levels of serum oxidative stress and telomerase in children.

INTRODUCTION: Electrical burns cause significant morbidity and mortality worldwide. Here we measured changes in levels of serum oxidative stress and telomerase in children suffering from high-voltage electrical burn (HVEB) injuries and other burns and the significance of these parameters in terms of amputation. MATERIALS AND METHODS: After obtaining approval from our ethics committee for this prospective study, we formed three groups: a group of 18 children with HVEBs, a group of 18 children with thermal burns, and a control group. All children were 1-16 years of age. The HVEB group was divided into HVEB-WA (without amputation) and HVEB-A (with amputation) subgroups. Serum malondialdehyde (MDA) level, total antioxidant capacity (TAC), total oxidant capacity (TOC), glutathione (GSH) level, and telomerase level were measured and compared among the groups. RESULTS: The patients differed in terms of demographics. The healing time of the HVEB group was longer than that of the thermal burn group, and the oxidative stress indicators of the HVEB group remained higher for longer. The mean oxidative stress indices in the HVEB-A group were higher than those in the HVEB-WA group and remained elevated for longer. CONCLUSION: HVEBs are more destructive than thermal burns; damage may progress over time, and healing takes longer. Healing can be followed biochemically by measuring levels of oxidative stress indicators. Indications for amputation, if not initially obvious, can be predicted by evaluating these indicators, affording therapeutic advantages.

Attenuation of ureteral obstruction-induced renal injury by polyenylphosphatidylcholine.

BACKGROUND: The cytoprotective, antioxidant and antifibrotic effects of polyenylphosphatidylcholine (lecithin, PPC) have been demonstrated both experimentally and clinically. The present study investigated whether PPC treatment has any beneficial effect on renal injury in unilateral partial ureteral obstruction (UUO) in rats. METHODS: Forty Wistar-Albino rats were split into three groups (sham-operated controls, untreated and treated rats). Rats of the untreated and treated groups (n = 15) underwent UUO with two-thirds of the left ureter embedded in the psoas muscle. In group 3, PPC was given orally at a dose of 100 mg/day for 30 days. At the end of the 30th day of the experimental period, obstructed kidneys and blood samples were harvested. To investigate the therapeutic efficacy of PPC treatment in UUO kidneys, oxidant and antioxidant enzyme levels, lipid peroxidation, proinflammatory cytokines (interleukin-1, interleukin-6, tumor necrosis factor alpha), transforming growth factor beta-1 (TGFbeta-1), alpha smooth muscle actin (alpha-SMA) and nuclear factor kappa beta (NF-kappabeta) expression, leukocyte infiltration (ED1, ED2, CD4 and CD8 immunohistochemistry), and tubulointerstitial damage in the obstructed kidneys were studied. RESULTS: Oxidative stress, neutrophil infiltration, release of cytotoxic mediators, TGFbeta-1 levels, tubulointerstitial damage, alpha-SMA and NF-KB expressions in kidney tissue were significantly increased in the UUO rats. PPC treatment attenuated oxidative stress, leukocyte infiltration, cytotoxic mediator, and TGFbeta-1 levels and also decreased expressions of alpha-SMA and NF-kappabeta. It was associated with decreased tubulointerstitial damage, compared with UUO alone. CONCLUSIONS: These results indicate that PPC treatment protects against UUO-induced renal injury in rats possibly through its antioxidant, anti-inflammatory and antifibrotic actions.

Sulfasalazine reduces inflammatory renal injury in unilateral ureteral obstruction.

The purpose of this study was to test whether sulfasalazine has a protective action against interstitial inflammation and the development of renal fibrosis in obstructive nephropathy. Female rats were subjected to a sham (n = 10) or unilateral ureteral obstruction (UUO, n = 30). UUO was induced in rats by ligating the left ureter. Three days after operation, rats subjected to UUO were randomized to receive tretment with either sulfasalazine (100 mg/kg) or vehicle every day for the last 7 days of the experiment. At 10 days following UUO, the obstructed kidney exhibited tubulointerstitial injury and leukocyte infiltration (mainly monocytes) that were associated with high levels of reactive oxygen species, cytokines, transforming growth factor (TGF)-beta1, myeloperoxidase (MPO), and lipid peroxidation. Ten days after UUO, the obstructed kidney was also associated with increased nuclear factor kappa beta (NF-kappabeta) expression in saline-treated rats. Compared with sham-operated rats, UUO rat kidneys showed lower concentrations of antioxidant enzymes in the obstructed kidney tissue. All of these changes were significantly attenuated by treatment with sulfasalazine in the obstructed kidney. Sulfasalazine protected against the renal interstitial inflammation and tissue damage elicited by ureteral occlusion. Inhibition of the NF-kappabeta-dependent pathway and inflammatory response and oxidative stress inhibition is likely to be involved in the beneficial effects of sulfasalazine.

Fluvastatin reduced liver injury in rat model of extrahepatic cholestasis.

Inhibitors of 3-hydroxy-3methylglutarly coenzyme A, reductase, namely statins, exert pleiotropic actions beyond lipid-lowering effects. In ex vivo and in vitro studies, statins have antioxidative and antiinflammatory effects. Herein, we sought to determine whether treatment with fluvastatin (FV) would be beneficial in a rat model of common bile duct ligation (BDL)-induced liver injury. Female rats were subjected to a sham (n=10) or BDL (n=20). Obstructive jaundice was induced in rats by the ligation and division of the common bile duct. Three days after operation, rats subjected to CBDL were randomized to receive treatment with either FV (10 mg/kg) or saline every day over a 10 days experimental period. High levels of alanine aminotransferase, aspartate aminotransferase, and gamma glutamyltransferase decreased significantly (P<0.05) in animals treated with FV with compared to saline-administrated BDL animals. Compared with sham-operated rats, CBDL rats showed significantly higher levels of total nitrite and nitrate, malondihaldehyde, tumor necrosis factor alpha, myeloperoxidase, and lower concentrations of glutathione, superoxide dismutase, and catalase in the liver tissue (P<0.001). All of these changes were significantly attenuated (P<0.05) by treatment with FV after CBDL. CBDL was associated with increased apoptosis and nuclear factor kappa beta expression in saline-treated rats. Treatment with FV also decreased these parameters. These data support the view that FV ameliorates hepatic inflammation, lipid peroxidation, and tissue injury in rats subjected to CDBL. FV warrants further evaluation as an adjunctive treatment to ameliorate liver injury from extrahepatic biliary obstruction.

The NF-kappaB inhibitors attenuate hepatic injury in bile duct ligated rats.

Cholestasis-induced liver injury during bile duct obstruction causes an inflammatory response and this inflammatory process may be an important source of tissue injury. We hypothesized that NF-kappaB inhibition would decrease liver injury in a rat model of extrahepatic biliary obstruction. A total of 40 female rats of Sprague-Dawley strain were allocated to four groups. First group was sham operated control. The second group underwent common bile duct ligation (BDL) and was monitored for 10 days. Third group of rats underwent BDL and received pyrrolidine dithiocarbomate (PDTC) at a dose of 100 mg/kg/day intraperitoneally. Fourth group underwent BDL and received sulfasalazine at a dose of 100 mg/kg b.w. Both inhibitors were administered once a day throughout last 7 days of the experimental period. Rats were terminated 10 days after sham operation or BDL. Aspartate aminotransferase, alanine aminotransferase, gamma-glutamil transpeptidase, and tumor necrosis factor-alpha levels were elevated in the BDL group as compared to the control group, while this increase was significantly decreased by treatment with PDTC and sulfasalazine (P < 0.05). Hepatic GSH, SOD and catalase levels were significantly depressed by BDL, but were elevated back to control levels in NF-kappaB inhibitor-treated BDL groups. Increases in tissue free radical and MDA levels and MPO activity due to BDL were reduced back to control levels by NF-kappaB inhibitor treatment (P < 0.05). Similarly histological damage in the BDL rats was reduced by treatments. These results indicate that inhibitors of NF-kappaB activity such as PDTB and sulfasalazine exert a therapeutic effect on cholestatic liver injury in rats with BDL through anti-inflammatory and antioxidant actions.