The effect of silymarin on hepatic regeneration after partial hepatectomy: is silymarin effective in hepatic regeneration?

AIM: Silymarin from Silybum marianum was found to reduce liver injury. The aim of the present study was to investigate the effects of silymarin on hepatic regeneration in partially hepatectomized rats. METHODS: Thirty Wistar-Albino rats were divided into 3 groups of 10 animals as sham, control and experimental groups. In the sham group (n=10) abdominal incision was closed after laparotomy. In the control group (n=10), the rats underwent 70% hepatectomy after laparotomy. In the experimental group (n=10) after partial 70% hepatectomy, silymarin (200 mg/kg/d) were given to rats for 10 days. Rats in three groups were sacrificed on 10 days. Aspartate (AST) and alanine transaminase (ALT), gamma glutamyl transferase (GGT), ALP, LDH and total bilirubin levels were measured using intracardiac blood samples. Tissue malondialdehyde (MDA) and tissue glutathion (GSH) and Superoxide dismutase (SOD) levels were measured. To reveal the increase in the mass of the remnant liver tissue in the control and experimental groups relative weight of the liver was calculated. Histopathological analysis of the liver was performed using a semi-quantitative scoring system. RESULTS: A statistically significant difference among three groups was not shown for AST and ALT levels. A statistically significant difference was found between the groups as for total bilirubin and gamma glutamyl transferase levels. Increases in relative liver weights were seen with time in Groups 2 and 3. A statistically significant difference was not found for tissue malondialdehyde, Glutathion and Superoxide dismutase levels between hepatectomy and hepatectomy + silymarin groups. On liver tissue sections of the rats in the hepatectomy + silymarin group, increased regeneration and lipid peroxidation were observed accompanied by decreased antioxidant response. CONCLUSION: It has been observed that silymarin with many established functions such as antiproliferative, anti-inflammatory and energy antioxidant effects, does not contributed to proliferative regeneration of the liver-which has very important metabolic functions -after partial hepatectomy; instead it will decrease serum levels of transaminases.

The effect of polymorphism in DNA repair genes RAD51 and XRCC2 in colorectal cancer in Turkish population.

The genes RAD51 and XRCC2 encode proteins that are important for the repair of double-strand DNA breaks by recombination. Therefore, genetic variability in these genes may contribute to the occurrence and progression of carcinoma. We investigated the association of polymorphisms in the DNA repair genes XRCC2-A/G and RAD51-135G/C with the colorectal cancer risk. Genotypes were determined by PCR-RFLP assays in 71 patients with colorectal cancer and 86 age-matched healthy controls. After amplification, we used a restriction enzyme (RAD51; MvaI and XRCC2; HphI) and digested the PCR product. Then, this DNA fragments were passed through gel electrophoresis. By examining these images, we identified changes in the nucleotides in these specific regions. To clarify fragments polymorphisms, the PCR products were sequenced with an Applied Biosystems Automated Sequencer. We observed the Arg188His polymorphism of XRCC2 genes in 42.2%, as shown in 30 of the 71 cancer patients. Only 21 out of 86 controls showed this polymorphism (24.2%). We also observed that 21 of the 71 patients (29.5%) carried the RAD51135G/C polymorphism of this gene. The same polymorphism was observed in 11 of the 86 controls (12.7 %; p < 0.05). The obtained results indicate that the polymorphism of RAD51 and XRCC2 genes may be associated with the incidence of colon cancer in the Turkish population. Further studies, including those on a larger group of patients, are required to further clarify this point.

Tamoxifen citrate: a glimmer of hope for silicosis.

BACKGROUND: Inhalation of crystalline silica nanoparticles causes pulmonary damage resulting in progressive lung fibrosis. Currently, there is no effective treatment for silicosis. Tamoxifen citrate is a selective estrogen receptor modulator, which is one of the adjuvant treatment choices for breast cancer. It is also known with its inhibitory effect on the production of transforming growth factor-beta (TGF-ß) and studied for the anti-fibrotic effect in some fibrotic diseases. The aim of the study was to determine the effect of tamoxifen citrate on the prevention of pulmonary fibrosis and the treatment of silicosis. METHODS: A total of 100 adult female Wistar Albino rats (200-250 g) were used in this study. The rats were divided into five groups including 20 rats in each. Rats were exposed to silica for 84 d in all groups. In group 1, rats were sacrificed on the day 84 without receiving treatment. In group 2, rats received 1 mg/kg tamoxifen (tmx1 + 1), from the first day of the study for the whole 114 d of the study. In group 3, (tmx10 + 10) rats were given 10 mg/kg tamoxifen from the first day of the study for the whole 114 d of the study. In group 4 (tmx1), rats were started 1 mg/kg of tamoxifen on day 84 and were given until day 114. In group 5 (tmx10), rats were fed with 10 mg/kg tamoxifen starting from day 84 to day 114. All rats except group 1 were sacrificed on 114 day of the study. Lung inflammation and fibrosis scores, serum TGF ß levels, lung smooth muscle antigen and tissue transforming growth factor ß (t-TGF-ß) antibody staining levels, and number of silicotic rats were compared between groups. RESULTS: Silicosis was caused successfully in all rats in group 1. There were six silicotic rats in group 3 and it was the lowest number of all groups. Plasma TGF-ß levels and fibrosis score were significantly lower in all groups when compared with the control group. Tamoxifen could have preventive or treating effects in silicosis and found that lung fibrosis score was significantly lower in rats treated with tamoxifen. CONCLUSIONS: Tamoxifen treatment after and/or before induction of silicosis decreased lung fibrosis score with blood TGF-ß levels. We hope that this study may introduce a new indication as prophylactic use of tamoxifen in high-risk groups for silicosis and for treatment of silicosis.

Polymorphisms in DNA repair genes XRCC2 and XRCC3 risk of gastric cancer in Turkey.

We studied the prevalence of polymorphisms in genes XRCC2 and XRCC3 in stomach cancer patients who lived in North Eastern Turkey. A total of 61 cancer patients and 78 controls were included in this study. Single nucleotide changes were studied in XRCC2 and XRCC3 genes at locus Arg188His and Thr241Met. Blood samples were taken from the patients and controls, and DNA was isolated. The regions of interest were amplified using a polymerase chain reaction method. After amplification, we used restriction enzymes (HphI and NcoI) to digest the amplified product. Digested product was then run through gel electrophoresis. We identified changes in the nucleotides in these specific regions. It was found that the Arg188His polymorphism of the XRCC2 gene was about 39% (24 out of the 61) among cancer patients. However, only 15% (12 out of 78) of the control group indicated this polymorphism. We also observed that 18 of the 61 cancer patients (29%) carried the Thr241Met polymorphism of the XRCC3 gene whereas 11 of the 78 (14%) individuals in the control group had the polymorphism. Our results showed a significant difference in polymorphism ratios between the cancer patients and health control group for the regions of interest. This result clearly showed that these polymorphisms increase the risk of stomach cancer and might be a strong marker for early diagnosis of gastric cancer.

Effects of hyperglycemia on the developing brain in newborns.

BACKGROUND: Hyperglycemia is a common problem in preterm neonates and is associated with increased risk of mortality and severe morbidities such as brain damage. However, available data about the effects of severity of hyperglycemia on the developing brain in the early life is limited. Therefore, we evaluated the effects of moderate and severe hyperglycemia on the developing brain. METHOD: Thirty newborn Sprague-Dawley rats were randomly divided into three groups as control, moderate hyperglycemia (30% dextrose), and severe hyperglycemia (50% dextrose). Pups in the hyperglycemia groups were administered subcutaneous sterile dextrose solution at a dose of 4 mL/kg daily from the second day to the eleventh day of life. Blood glucose levels were measured every day in all study groups. Rat brain tissues were removed at the end of the study. Histopathologic and immunohistochemical (caspase-9, -8, and -3) examination and biochemical analysis including xanthine oxidase, total antioxidant status, total oxidant status, and malondialdehyde activities were performed. RESULTS: Weight of the brain tissues in rats with hyperglycemia groups was significantly lower than the control group (P < 0.05). Weight of the brain tissues in rats with moderate hyperglycemia was lower than that of the severe hyperglycemia (P < 0.05). In the histopathologic and immunochemical evaluation, severity of brain damage and apoptosis were significantly higher in the severe hyperglycemia group, especially at the level of the hippocampus (P < 0.05). Tissue malondialdehyde, xanthine oxidase levels, and total oxidant status were significantly increased in the severe hyperglycemia group, whereas total antioxidant status was significantly decreased in the severe hyperglycemia group (P < 0.001). CONCLUSION: Brain damaging effects of severe hyperglycemia were observed in the developing brains of the rat pups. It might be inferred that severe hyperglycemia can damage the developing brain especially in preterm infants.

Protective role of heparin in the injury of the liver and kidney on the experimental model of ischemia/reperfusion.

BACKGROUND: Surgery of thoracoabdominal aortic aneurysms (TAAA) is associated with high incidence of serious complications. Ischemia/reperfusion (I/R) injury may be responsible for these complications. We investigated the effect of degree of anticoagulation on remote organ I/R injuries and whether heparin is protective against I/R injury in addition to its anticoagulant properties. METHODS: Spraque Dawley rats were used to determine both liver and kidney concentrations of HSP-70,IL-6, MPO in four groups: ischemic control (operation with cross-clamping and intraperitoneal administration of 0.9% saline, n = 7), sham (operation without cross-clamping, n = 7), heparin (ACT level about 200), and high dose heparin (ACT level up to 600). Histological analyses of the organs were performed. RESULTS: Histopathological evaluation of kidney presented significant differences between groups with regards to the cytoplasmic vacuole formation, hemorrhage, tubular cell degeneration and tubular dilatation while heparinized group had best results. The kidney MPO and HSP-70 levels significantly decreased (p < 0.05), but IL-6 level was not significant (p > 0.05) in heparinized group when compared to ischemic control group. No statistically significant intergroup differences were detected in the tissue samples of liver. Immunohistochemical markers of the liver were compared and no statistically significant difference was found among the groups. CONCLUSION: Heparin is an important anticoagulation agent in TAAA surgical procedures but the use of higher levels of heparin in the present study revealed no beneficial effects. Bleeding complications is much less when heparin is used in the real-world clinical practice as ACT levels of 200.

The protective effect of amiodarone in lung tissue of cecal ligation and puncture-induced septic rats: a perspective from inflammatory cytokine release and oxidative stress.

Sepsis is a serious medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. Amiodarone is a class III antiarrhythmic agent, a multichannel blocker (Ca++, Na+, and K+), and a noncompetitive α- and ß-adrenergic blocker in cardiac cells. The present study aimed to determine whether amiodarone was protective against experimentally induced cecal ligation and puncture sepsis in rat lung tissue. The relationship between its probable protective effect and antioxidant/anticytokine action biochemically and histopathologically was also examined. Five groups of rats were used, each composed of 20 rats: (1) the sham-operated control group; (2) the CLP group; (3) the 25-mg/kg amiodarone-treated control healthy group; (4) the 50-mg/kg amiodarone-treated CLP group; and (5) the 50-mg/kg amiodarone-treated CLP group. A CLP polymicrobial sepsis model was applied to the rats. All groups were sacrificed 16 h later, and lung and blood samples were analyzed histopathologically and biochemically. Twenty-five and 50 mg/kg amiodarone decreased the level of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α in serum and 8-iso-prostaglandin F2α level in lung tissue. They increased the activities of superoxide dismutase and levels of total glutathione in lung tissues of rats. Histopathological scores and examinations were in accordance with the biochemical results. Histopathological analysis revealed significant differences in inflammation scores between the sepsis group and the other groups. The CLP + amiodarone 50 mg/kg group had the lowest inflammation score among CLP groups. Our results indicate that administration of amiodarone prevented oxidative stress and cytokine action and protected lung tissue during sepsis cascade.

Effects of tamoxifen citrate on postoperative intra-abdominal adhesion in a rat model.

BACKGROUND/AIMS: The aim of this study was to evaluate the effects of oral tamoxifen citrate on postoperative intra-abdominal adhesions. MATERIALS AND METHODS: Forty five rats were randomly separated in to 3 groups. Group 1: Control group (15 rats), Group 2: tmx 1 group (15 rats) and Group 3: tmx 10 group (15 rats). The cecum was abraded with a sterile gauze until subserosal hemorrhage had developed. Full- thickness 4-0 silk sutures were also placed in the traumatized anterior cecal wall to increase the adhesive reaction. In Group 1 (control group), adhesion induction was performed and no treatment was given. In Group 2 (tmx 1 group), after adhesion induction, 1 mg/kg/day tamoxifen citrate was given by orogastric gavage. In Group 3 (tmx 10 group), adhesion induction was performed and 10 mg/kg/day tamoxifen citrate was given by orogastric gavage. Rats were sacrificed on postoperative day 30. At the time of second surgery, after the abdominal fascia had been opened blood samples were collected to evaluate serum TGFß-1 levels and following the macroscopic adhesion scoring, tissue specimens of the bowel and adhesions were subjected to histopathological investigation. RESULTS: In group 1 and group 2 we detected higher scores for the macroscopic classification (2.25 ± 1.13 vs. 1.53 ± 0.77) and histopathological scores (2.72 ± 0.64 vs. 2.53 ± 0.87) for fibrosis and serum TGFß-1 levels (42000 ± 2935 vs. 32988 ± 10804). In group 3 we have detected decreased scores for macroscopic classification (0.91 ± 0.51) and histopathological scores (1.58 ± 0.90) for fibrosis and serum TGFß-1 levels (22847 ± 4976). There were no significant differences between group 1 and group 2 according to the macroscopic classification and pathological scores for fibrosis. There were statistically significant difference between tamoxifen 10 mg/kg group and the other groups according to macroscopic classification ( P: G1-3: 0.004; G2-3: 0.046), pathological scores for fibrosis (P: G1-3: 0.004; G2-3: 0.011) and serum TGFß-1 levels (P: G1-3:<0.001). CONCLUSIONS: In conclusion tamoxifen citrate seems to be useful for preventing postoperative intra-abdominal adhesions. Its effects are in a dose and time dependent manner. Further studies must be carried out to use tamoxifen for preventing intra-abdominal postoperative adhesions in clinical practice.

Comparison of short-term results of modified Karydakis flap and modified Limberg flap for pilonidal sinus surgery.

The aim of this study was to compare and analyze the short term results of modified Karydakis flap reconstruction (MKF) and modified Limberg flap reconstruction (MLF). This is a retrospective analysis of 81 patients operated for pilonidal sinus disease. There were 46 patients in MLF group and 35 patients in MKF group. We compared patients age, BMI, operation time, removal time of suction drain, time of feeling completely healed, type of presentation, complications, postoperative 1., 3., 5. Days VAS scores, time to stop analgesic drugs and time to sit on chair or throne without pain. Complication rate, analgesic drug stopping time, postoperative 5. days VAS score were lower in MLF group and there were significant difference between groups. MLF group patients feel better (P: 0.010), they recommended this operation to other pilonidal sinus patients (P: 0.010) and 36 of them rated their satisfaction excellent and 10 of them good (P: 0.010). MLF procedure was more comfortable for patients. Lesser pain, lower complication and recurrence rates and higher patient satisfaction were detected in MLF group.

Diagnosis and treatment of multiseptate gallbladder with recurrent abdominal pain.

Laparoscopic cholecystectomy is usually performed for gallstones or polyp of the gallbladder. Multiseptate gallbladder is a rare congenital malformation. Although several asymptomatic cases have been described, patient usually present with right upper abdominal pain. We present a 29-year-old female patient with multiseptate gallbladder, cholecystectomy was performed, and her abdominal pain and gastrointestinal complaints have resolved.