Genistein and Sex Hormone Supplementation Modulated Hepatic PPARα, δ, and γ Subtypes and STAT1 Expressions in a NASH Rat Model with Bilateral Orchidectomy.

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) that is characterized by hepatic inflammation and steatosis. Currently, limited data exist regarding the risk of NASH in transgender women and the treatment options for this particular population. The use of testosterone supplementation is unfavorable for transgender women, and estrogen supplementation is linked to an increased risk of breast cancer; thus, an isoflavone derivative compound known as "genistein" could serve as a viable substitute for a hormone supplement in this context. The purpose of this study was to investigate the treatment effects and mechanisms of actions of genistein and sex hormones in orchidectomized (ORX) rats with nonalcoholic steatohepatitis induced via a high-fat high-fructose diet (HFHF) model. Male Sprague-Dawley rats (n = 42) were randomly assigned into seven groups; control, ORX + standard diet, HFHF, ORX + HFHF, ORX + HFHF diet + testosterone (50 mg/kg body weight (BW) once weekly), ORX + HFHF diet + estradiol (1.6 mg/kg BW daily), and ORX + HFHF diet + genistein (16 mg/kg BW daily). The duration of the study was 6 weeks. Some parts of liver tissue were used for histological examination by H&E staining. The determination of fat accumulation was performed using Oil Red O staining. SREBP1c and FAS gene expression were quantified using real-time PCR technique. The levels of all types of peroxisome proliferator-activated receptors (PPARs; α, δ, γ), proteins, and signal transducer and activator of transcription 1 (STAT1) signaling pathway were determined by both immunoblotting and immunohistochemistry. Rats in the ORX + HFHF group had the highest degree of hepatic steatosis, lobular inflammation, and hepatocyte ballooning, and showed higher levels of genes related to de novo lipogenesis, including SREBP1c and FAS. The expression of PPARγ and STAT1 were upregulated, while the expression of PPARα and PPARδ were downregulated in the ORX + HFHF group. Testosterone, estradiol and genistein treatments improved NASH histopathology together with the reversal of all types of PPAR protein expressions. Interestingly, genistein decreased the levels of STAT1 protein expression more than those of testosterone and estradiol treatment. Genistein and sex hormone treatment could ameliorate NASH through the upregulation of PPARα, and PPARδ, and the suppression of PPARγ and STAT1 expression.

Genistein and sex hormone treatment alleviated hepatic fat accumulation and inflammation in orchidectomized rats with nonalcoholic steatohepatitis.

Testosterone deficiency has been reported to accelerate nonalcoholic fatty liver disease (NAFLD). However, there are minimal data on the risk of NAFLD in transgender women and the treatment of NAFLD in this population. This study aimed to investigate the treatment effects and the mechanisms of action of genistein and sex hormones in orchiectomized (ORX) rats with nonalcoholic steatohepatitis (NASH) induced by a high fat high fructose diet (HFHF). Seven-week old male Sprague-Dawley rats were randomly divided into 7 groups (n = 6 each group); 1) control group, 2) ORX + standard diet group, 3) HFHF group, 4) ORX + HFHF group, 5) ORX + HFHF diet + testosterone group (50 mg/kg body weight (BW) once weekly), 6) ORX + HFHF diet + estradiol group (1.6 mg/kg BW daily), and 7) ORX + HFHF diet + genistein group (16 mg/kg BW daily). The duration of treatment was 6 weeks. Liver tissue was used for histological examination by hematoxylin and eosin staining and hepatic fat measurement by Oil Red O staining. Protein expression levels of histone deacetylase3 (HDAC3) and peroxisome proliferator-activated receptor delta (PPARδ) were analyzed by immunoblotting. Hepatic nuclear factor (NF)-ĸB expression was evaluated by immunohistochemistry. Rats in the ORX + HFHF group had the highest degree of hepatic steatosis, lobular inflammation, hepatocyte ballooning and the highest percentage of positive Oil Red O staining area among all groups. The expression of HDAC3 and PPARδ was downregulated, while NF-ĸB expression was upregulated in the ORX + HFHF group when compared with control and ORX + standard diet groups. Testosterone, estradiol and genistein treatment improved histological features of NASH together with the reversal of HDAC3, PPARδ and NF-ĸB protein expression comparing with the ORX + HFHF group. In summary, genistein and sex hormone treatment could alleviate NASH through the up-regulation of HDAC3 and PPARδ, and the suppression of NF-ĸB expression.

Calcitriol Protects against Acetaminophen-Induced Hepatotoxicity in Mice.

Acetaminophen (APAP) overdose is one of the major causes of acute liver failure. Severe liver inflammation and the production of oxidative stress occur due to toxic APAP metabolites and glutathione depletion. Growing evidence has proved that vitamin D (VD) exerts anti-inflammatory and antioxidative functions. Our objective was to explore the protective role of calcitriol (VD3) in acute APAP-induced liver injury. Methods: Adult male mice were randomized into three groups; control (n = 8), APAP (n = 8), and VD3 group (n = 8). All mice, except controls, received oral administration of APAP (400 mg/kg) and were sacrificed 24 h later. In the VD3 group, calcitriol (10 µg/kg) was injected intraperitoneally 24 h before and after exposure to APAP. Blood samples were collected to assess serum aminotransferase and inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6)]. Liver tissues were analyzed for hepatic glutathione (GSH), malondialdehyde (MDA), and histopathology. Results: APAP administration significantly increased serum aminotransferase, inflammatory cytokines, and induced cellular inflammation and necrosis. APAP also depleted hepatic GSH and elevated oxidative stress, as indicated by high MDA levels. In the APAP group, 25% of the mice (two out of eight) died, while no deaths occurred in the VD3 group. Treatment with calcitriol significantly reduced serum aminotransferase, TNF-α, and IL-6 levels in the VD3 group compared to the APAP group. Additionally, VD3 effectively restored GSH reserves, reduced lipid peroxidation, and attenuated hepatotoxicity. Conclusions: These findings demonstrate that VD3 prevents APAP-induced acute liver injury and reduces mortality in mice through its anti-inflammatory and antioxidative activity. Thus, VD3 might be a novel treatment strategy for APAP-induced hepatotoxicity.

The prevalence and treatment outcomes of Helicobacter pylori infection in a tertiary hospital in Thailand, 2018-2021.

Background and Aim: Helicobacter pylori (HP) infection remains a significant global public health problem. This study aimed to study the prevalence of HP infection and treatment outcomes in Thailand. Methods: We retrospectively reviewed the results of the urea breath test (UBT) performed at the King Chulalongkorn Memorial Hospital between 2018 and 2021. The prevalence of HP infection was evaluated in dyspeptic patients undergoing UBT screening. In patients with known HP infection, the treatment regimen and the success rate in each patient were recorded. Results: One-thousand nine-hundred and two patients were included in this study. The prevalence of HP infection in dyspeptic patients was 20.77% (UBT was positive in 65 out of 313 patients). Of the 1589 patients who received the first treatment regimen, 1352 (85.08%) had a negative UBT result. Patients who failed in each treatment regimen were treated with subsequent regimens. The overall success rates for the second, third, and fourth regimens were 69.87% (109 of 156 patients), 53.85% (14 of 26 patients), and 50% (3 of 6 patients), respectively. Univariate logistic regression analysis found that using lansoprazole was associated with failure of treatment with OR = 2.11 (95% CI: 1.14-3.92, P = 0.018). Conclusion: Current primary HP treatment regimens have an eradication rate of >80%. Even though the previous regimens failed, without available antibiotic sensitivity results, the subsequent regimens were successful by at least 50%. In cases of multiple-treatment failure and where antibiotic sensitivity tests were unavailable, continuing to change regimens could provide satisfactory results.

Effects of probiotics on pancreatic inflammation and intestinal integrity in mice with acute pancreatitis.

BACKGROUND: Severe acute pancreatitis is a potentially life-threatening disease. Despite being a common disorder, acute pancreatitis lacks a specific treatment. The present study aimed to examine the effects of probiotics on pancreatic inflammation and intestinal integrity in mice with acute pancreatitis. METHODS: Male ICR mice were randomly divided into 4 groups (n = 6 per group). The control group received two intraperitoneal (i.p.) injections of normal saline as a vehicle control. The acute pancreatitis (AP) group received two i.p. injections of L-arginine 450 mg/100 g body weight. AP plus probiotics groups received L-arginine to induce acute pancreatitis as above. In the single-strain and mixed-strain groups, mice received 1 mL of Lactobacillus plantarum B7 1 × 108 CFU/mL and 1 mL of Lactobacillus rhamnosus L34 1 × 108 CFU/mL and Lactobacillus paracasei B13 1 × 108 CFU/mL by oral gavage, respectively for 6 days starting 3 days prior to the AP induction. All mice were sacrificed 72 h after L-arginine injection. Pancreatic tissue was obtained for histological evaluation and immunohistochemical studies for myeloperoxidase, whereas ileal tissue was used for immunohistochemical studies for occludin, and claudin-1. Blood samples were collected for amylase analysis. RESULTS: Serum amylase levels and pancreatic myeloperoxidase levels in the AP group were significantly higher than in controls and significantly decreased in probiotic groups compared with the AP group. Ileal occludin and claudin-1 levels were significantly lower in the AP group than in controls. Ileal occludin levels significantly increased, whereas ileal claudin-1 levels did not significantly change in both probiotic groups as compared with the AP group. The pancreatic histopathology showed significantly higher degree of inflammation, edema, and fat necrosis in the AP group, and these changes improved in mixed-strained probiotic groups. CONCLUSIONS: Probiotics, particularly the mixed-strain ones, attenuated AP via the reduction of inflammation and the maintenance of intestinal integrity.

Student academic performance in non-lecture physiology topics following the abrupt change from traditional on-site teaching to online teaching during COVID-19 pandemic.

BACKGROUND: During the COVID-19 pandemic, pre-clerkship medical education, including all physiology classes, was obliged to change to online teaching due to limitations of on-site (face-to-face) classes. However, the effectiveness of online teaching in non-lecture physiology topics during the COVID-19 pandemic has not been thoroughly investigated. METHOD: We conducted a prospective study to evaluate the students' academic achievement and opinions on online teaching during the COVID-19 academic year. Academic achievement of 312 students in the COVID-19 year was compared with that of 299 students in the pre-COVID-19 year. Student opinions regarding social interactions and the preferred learning method were also collected. RESULTS: We found that student academic achievement in the non-lecture physiology topics, assessed by summative scores, was 4.80±0.92 percent higher in the pre-COVID-19 year than in the COVID-19 year (P < 0.01, Cohen's d = 0.42). Students rated that online classes tended to reduce their interactions with peers and teachers; however, students preferred online learning over traditional on-site learning. CONCLUSIONS: This study pointed out that students' academic performance related to the physiology topics taught by online non-lecture methods during the COVID-19 pandemic was lower than their performance when the topics were taught by the traditional (on-site) methods, although students reported that they preferred the online teaching. Hence, we suggest that medical teachers should deliberately plan and utilise a variety of tools and techniques when developing online non-lecture classes to preserve the interactivity of the classes, which might overcome this gap in students' academic performance.

Genistein attenuated oxidative stress, inflammation, and apoptosis in L-arginine induced acute pancreatitis in mice.

AIM: Acute pancreatitis is a common and potentially serious condition. However, a specific treatment for this condition is still lacking. Genistein, with its anti-oxidant and anti-inflammatory effects, could possibly be used to tackle the underlying pathophysiology of acute pancreatitis. Therefore, the aim of this study was to investigate the effects of genistein on oxidative stress, inflammation, and apoptosis in acute pancreatitis induced by L-arginine in mice. METHODS: Twenty-four male ICR mice were equally divided into 4 groups: Control (Con); Acute pancreatitis (AP) group: Two doses of i.p. 350 mg/100 g body weight (BW) of L-arginine were administered 1 h apart; AP and low-dose genistein (LG) group: mice were given i.p. injection of 10 mg/kg genistein 2 h prior to L-arginine injection followed by once-daily dosing for 3 days; and AP and high-dose genistein (HG) group: mice were given 100 mg/kg genistein with the similar protocol as the LG group. Pancreatic tissue was evaluated for histopathological changes and acinar cell apoptosis, malondialdehyde (MDA) levels, immunohistochemical staining for myeloperoxidase (MPO), nuclear factor-kappa beta (NF-kB), and 4-hydroxynonenal (4-HNE). Serum levels of amylase (AMY), c-reactive protein (CRP), and interleukin (IL)-6 were measured. RESULTS: Significant increases in the degree of acinar cell apoptosis, pancreatic MDA, serum IL-6 and amylase, MPO, NF-kB and 4-HNE positivity were observed in the AP group. All these parameters declined after low- and high-dose genistein treatment. Severe pancreatic inflammation, edema, and acinar cell necrosis were observed in the AP group. Significant improvement of histopathological changes was seen in both low- and high-dose genistein groups. There were no significant differences in any parameters between low and high doses of genistein. CONCLUSION: Genistein could attenuate the severity of histopathological changes in acute pancreatitis through its anti-oxidant, anti-inflammatory, and anti-apoptotic properties.

Probiotics and their beneficial effects on alcohol-induced liver injury in a rat model: the role of fecal microbiota.

BACKGROUND: Current therapies for alcohol-induced liver injury are of limited efficacy and associated with significant side effects. With the proposed pathophysiology of alcohol-induced liver injury to be related to deranged gut microbiota, we hypothesized that probiotics would have beneficial effects in attenuating alcohol-induced liver injury. METHODS: Twenty-four male Sprague-Dawley rats were divided into 4 groups: control group, alcohol group, Lactobacillus plantarum group, and mixed-strain probiotics group. After 4 weeks, all rats were sacrificed, and blood samples were analyzed for ALT, lipopolysaccharide level (LPS), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Liver tissues were processed for histopathology, malondialdehyde (MDA) level and immunohistochemistry for toll-like receptors 4 (TLR-4). Stool samples were collected, and 16S rRNA sequencing was used to analyze the fecal microbiota. RESULTS: Liver histopathology showed the presence of significant hepatocyte ballooning in the alcohol group as compared with the control group, and the treatment with L. plantarum or mixed-strain probiotics alleviated these changes. Significant elevation of serum ALT, LPS, IL-6, and TNF-α, hepatic MDA levels, and hepatic TLR-4 expression were observed in alcohol-fed rats as compared with control rats. The administration of L. plantarum or mixed-strain probiotics restored these changes to the levels of control rats. The relative abundance of fecal bacteria at genus level showed a significant reduction in Allobaculum, Romboutsia, Bifidobacterium, and Akkermansia in the alcohol group as compared with the control group. In probiotics-treated rats, significant increases in Allobaculum and Bifidobacterium were observed, while the relative abundance of Romboutsia and Akkermansia was unchanged compared to the alcohol group. A reduction in alpha diversity was observed in alcohol-treated rats, whereas the improvement was noted after probiotic treatment. CONCLUSIONS: The treatment with Lactobacillus, whether as single-, or mixed-strain probiotics, was beneficial in reducing the severity of alcohol-induced liver injury likely through the increase in beneficial bacteria, and the reduction of inflammatory responses, and oxidative stress.

Thailand guideline 2020 for medical management of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is one of the most prevalent and bothersome functional gastrointestinal disorders worldwide, including in Thailand. After a decade of the first Thailand GERD guideline, physician and gastroenterologist encountered substantially increase of patients with GERD. Many of them are complicated case and refractory to standard treatment. Concurrently, the evolution of clinical characteristics as well as the progression of investigations and treatment have developed and changed tremendously. As a member of Association of Southeast Asian Nations, which are developing countries, we considered that the counterbalance between advancement and sufficient economy is essential in taking care of patients with GERD. We gather physicians from university hospitals, as well as internist and general practitioners who served in rural area, to make a consensus in this updated version of GERD guideline focusing in medical management of GERD. This clinical practice guideline was constructed adhering with standard procedure. We categorized the guideline in to four parts including definition, investigation, treatment, and long-term follow up. We anticipate that this guideline would improve physicians' proficiency and help direct readers to choose investigations and treatments in patients with GERD wisely. Moreover, we wish that this guideline would be applicable in countries with limited resources as well.

Genistein and exercise treatment reduced NASH related HDAC3, IL-13 and MMP-12 expressions in ovariectomized rats fed with high fat high fructose diet.

BACKGROUND AND AIM: Genistein (GEN) and exercise (Ex) may be regarded as an alternative treatment for non-alcoholic steatohepatitis (NASH). However, the mechanisms behind their therapeutic effects in NASH are not well-understood. EXPERIMENTAL PROCEDURE: This study investigated the roles of histone deacetylase (HDAC)3 and interleukin-(IL-)13 in the NASH model of ovariectomized (OVX) rats fed with high fat high fructose (HFHF) diet. RESULTS AND CONCLUSION: Nine weeks after being fed with HFHF diet, severe NASH pathology with mild fibrosis were seen along with an increase in HDAC3, IL-13 and matrix metalloelastase (MMP-12) expressions in OVX rats. Five weeks of either GEN or Ex treatments abrogated the increase in both HDAC3 and IL-13 expressions in OVX rats fed with HFHF diet and ameliorated NASH features, liver fibrosis and MMP-12 expression. The combination of Gen and Ex, however, did not provide additional benefits on NASH features in OVX rats fed with HFHF diet. These results suggested that GEN and Ex treatments improved HFHF diet induced NASH in OVX rats through the suppression of HDAC3, IL-13 and MMP-12 expression.

Changes of vitamin D receptors (VDR) and MAPK activation in cytoplasmic and nuclear fractions following exposure to cigarette smoke with or without filter in rats.

Cigarette smoke (CS) is a major cause of obstructive lung disease which is associated with significant disability and mortality. Vitamin D receptor (VDR) together with, mitogen activated protein kinases (MAPKs; ERK, JNK and p38) are the cellular transmission signals that mechanistically respond to CS and are recently found to have a role in lung pathogenesis. There are a few in vitro studies on subcellular VDR distribution involved MAPK but in vivo effects of cigarette smoke exposure with and without filter on this complex remain unclear. This study investigated subcellular VDR distribution and MAPK expression at early stages of both types of cigarette smoke exposure (CSE) in a rat model. Male Wistar rats were randomly divided into no-filter, filter and control groups. After 7 and 14 days of CSE, lung tissues were obtained to determine histopathology and protein expression. Cytoplasmic and nuclear VDR distribution significantly decreased on both CSE groups and corresponded with immunohistochemistry detection. The ratio of phosphorylated ERK to total ERK significantly increased in cytoplasm of both CSE on day 7. In particular, nuclear ERK MAPK significantly escalated in the filter group on day 14. In consistent with changes in intracellular markers, histopathological examination in both CSE groups showed significant increases in tracheal and peribronchiolar epithelial proliferation, alveolar macrophages and an increased trend of parenchymal infiltration. In summary, the evidence of lung injuries along with VDR depletion and MAPK activation observed in both CSE types indicated that there was no benefit of using cigarette filter to prevent protein damage or protect cells against cigarette smoke exposure in this model.

Genistein attenuated gastric inflammation and apoptosis in Helicobacter pylori-induced gastropathy in rats.

BACKGROUND: Helicobacter pylori (H. pylori) infection is a major cause of chronic gastritis, peptic ulcer diseases and cancer. Genistein (4',5,7-trihydroxyisoflavone), a tyrosine-specific-protein kinase inhibitor, has been shown to exert an anti-inflammatory property. The aim of this study was to examine the treatment effects of genistein and its mechanisms in rats with H. pylori infection. METHODS: Eighteen male Sprague-Dawley rats were divided into three groups (6 rats per group): (1) control group (Con); (2) H. pylori infected group (HP): the rats were inoculated with H. pylori (108- 1010 CFU/mL; 1 mL/rat.) for 3 consecutive days; and (3) HP + genistein group (HP + Gen): the rats were inoculated with H. pylori as above. Then, they were gavaged with genistein (16 mg/kg BW) for 14 days. Gastric tissue was used for the determination of nuclear factor (NF)-κB expression by immunohistochemistry (IHC), degree of apoptosis by the terminal deoxynucleotidyl transferasemediated dUTP nick-end labeling (TUNEL) reaction, and histopathology. Serum samples were used to measure the levels of tumor necrosis factor-alpha (TNF-α) and cytokine-induced neutrophil chemoattractant-1 (CINC-1). RESULTS: Rats in the HP group had significantly higher levels of pro-inflammatory mediators, NF-κB expression and apoptotic cells when compared with the Con group, and these markers significantly decreased in HP + Gen group when compared with the HP group. The histopathology of HP group showed moderate gastric inflammation and many HP colonization. Gastric pathology in HP + Gen group demonstrated the attenuation of inflammatory cell infiltration and H. pylori colonization. CONCLUSION: Genistein exerted its gastroprotective effects through the reduction of pro-inflammatory mediators, nuclear receptor NF-κB expression and gastric mucosal apoptosis in rats with H. pylori-induced gastropathy.

Anti-inflammatory and anti-oxidant effects of aloe vera in rats with non-alcoholic steatohepatitis.

BACKGROUND: Aloe vera exerts several biological activities, such as, anti-inflammatory, antioxidant, and antimicrobial effects. It was recently shown to reduce insulin resistance and triglyceride level. We hypothesized that aloe vera would have beneficial effects in alleviating non-alcoholic steatohepatitis (NASH) in rats. AIM: To examine the therapeutic effects of aloe vera in NASH rats. METHODS: All rats were randomly divided into 3 groups (n = 6 in each group). Rats in the control group were fed ad libitum with a standard diet for 8 wk. Rats in the NASH group were fed ad libitum with a high-fat high-fructose diet (HFHFD) for 8 wk. Rats in the aloe vera group were fed ad libitum with a HFHFD and aloe vera in dimethylsulfoxide (50 mg/kg) by gavage daily for 8 wk. Liver samples were collected at the end of the treatment period. RESULTS: Hepatic malondialdehyde (MDA) levels increased significantly in the NASH group as compared with the control group (377 ± 77 nmol/mg vs 129 ± 51 nmol/mg protein, respectively, P < 0.001). Glutathione (GSH) levels were significantly lower in the NASH group than the control group (9 ± 2 nmol/mg vs 24 ± 8 nmol/mg protein, respectively, P = 0.001). The expression of interleukin-18 (IL-18), nuclear factor-kappa ß, and caspase-3 increased, while peroxisome proliferator-activated receptor gamma decreased in the NASH group compared with the controls. Following aloe vera administration, MDA levels decreased (199 ± 35 nmol/mg protein) and GSH increased (18 ± 4 nmol/mg protein) markedly. Steatosis, hepatocyte ballooning, lobular inflammation and increased hepatocyte apoptosis were observed in the NASH group. Aloe vera treatment attenuated these changes in liver histology. CONCLUSION: Aloe vera attenuated oxidative stress, hepatic inflammation and hepatocyte apoptosis, thus improving liver pathology in rats with NASH.

Changes in inflammatory cytokines, antioxidants and liver stiffness after chelation therapy in individuals with chronic lead poisoning.

BACKGROUND: Chronic exposure to lead causes lead to accumulate mainly in the liver. In vivo studies have shown that lead toxicity is related to alterations in the inflammatory response. We aimed to evaluate the association between lead poisoning and liver fibrosis as well as the change in the degree of liver fibrosis, levels of inflammatory mediators and glutathione (GSH) after chelation therapy. METHODS: Workers from a battery factory who were exposed to lead for > 12 months and had a blood lead level (BLL) > 70 µg/dL were enrolled (n = 86) in the study. Participants underwent chelation therapy with intravenous CaNa2EDTA for 2 days followed by treatment with oral D-penicillamine for 90 days. The primary outcome was the change in the degree of liver fibrosis, which was presented as liver stiffness (LS) measured by FibroScan®. Secondary outcomes were the changes in the levels of serum GSH and inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) after chelation therapy. RESULTS: Among the 86 participants, there was a positive correlation between the duration of lead exposure and LS (r = 0.249, p = 0.021). To avoid the confounding effect of obesity-related steatosis, only 70 individuals who had controlled attenuation parameters < 296 dB/m, BMI < 25 kg/m2 and normal waist circumference were included in the interventional analysis. After chelation, the mean LS significantly decreased from 5.4 ± 0.9 to 4.8 ± 1.4 kPa (p = 0.001). Similarly, all of the inflammatory cytokines studied significantly decreased after chelation (p < 0.001); TNF-α decreased from 371.6 ± 211.3 to 215.8 ± 142.7; the levels of IL-1ß decreased from 29.8 ± 1.7 to 25.9 ± 4.3; and the levels of IL-6 decreased from 46.8 ± 10.2 to 35.0 ± 11.9. On the other hand, the mean GSH level increased significantly from 3.3 ± 3.3 to 13.1 ± 3.7 (p < 0.001) after chelation therapy. CONCLUSION: The duration of lead exposure was significantly correlated with the degree of liver fibrosis. Chelation treatment was associated with increased levels of GSH and decreased levels of proinflammatory cytokines and could potentially reduce the degree of LS. TRIAL REGISTRATION: This study was retrospectively registered and approved by the Thai Clinical Trial Registry (TCTR) on 2019-11-07. The TCTR identification number is TCTR20191108001 .

Genistein and exercise modulated lipid peroxidation and improved steatohepatitis in ovariectomized rats.

BACKGROUND: The prevalence of nonalcoholic steatohepatitis (NASH) in menopausal women is increasing, but current treatments have not been proven effective. The objective of this study was to investigate the treatment effects of genistein and running exercise in ovariectomized (OVX) rats with NASH. METHODS: Thirty-six female Sprague-Dawley rats were divided into 6 groups, control; OVX with standard diet; OVX with high fat and high fructose (HFHF) diet for 4 weeks; OVX with HFHF and genistein treatment (16 mg/kg BW/day) for 5 weeks (OVX + HFHF+GEN); OVX with HFHF and moderate intensity exercise for 5 weeks (OVX + HFHF+EX); OVX with HFHF and combined treatments (OVX + HFHF+GEN + EX). Serum interleukin-6 (IL-6) levels, hepatic free fatty acid (FFA), hepatic glutathione (GSH), and hepatic malondialdehyde (MDA) levels were measured. Liver histology was examined to determine NASH severity. RESULTS: OVX + HFHF group had the highest levels of hepatic FFA compared with OVX and control groups (5.92 ± 0.84 vs. 0.37 ± 0.01 vs. 0.42 ± 0.04 nmol/mg protein, respectively, p < 0.01). Serum IL-6 levels were significantly elevated in both OVX and OVX + HFHF groups as compared with controls (112.13 ± 6.50 vs. 121.47 ± 3.96 vs. 86.13 ± 2.40 pg/mL, respectively, p < 0.01). In OVX + HFHF group, hepatic MDA levels were higher, while GSH levels were lower than in OVX and control groups (MDA; 0.98 ± 0.04 vs. 0.82 ± 0.02 vs. 0.78 ± 0.03 nmol/mg protein, and GSH; 46.01 ± 0.91 vs. 55.21 ± 1.40 vs. 57.94 ± 0.32, respectively; p < 0.01 for both). Comparing with OVX + HFHF group, rats that received genistein, exercise and combined treatments demonstrated an improvement in liver histopathology, decreased levels of hepatic FFA (1.44 ± 0.21 vs. 0.45 ± 0.04 vs. 0.49 ± 0.05 nmol/mg protein, respectively, p < 0.01), serum IL-6 (82.80 ± 2.07 vs. 83.47 ± 2.81 vs. 94.13 ± 1.61 pg/mL, respectively, p < 0.01), and hepatic MDA (0.80 ± 0.03 vs. 0.76 ± 0.02 vs. 0.76 ± 0.03 nmol/mg protein, respectively, p < 0.01). CONCLUSIONS: Genistein and moderate intensity exercise were effective in reducing the severity of NASH in OVX rats through the reduction in liver inflammation, oxidative stress and liver fat contents.

Real-world data of Helicobacter pylori prevalence, eradication regimens, and antibiotic resistance in Thailand, 2013-2018.

BACKGROUND AND AIM: Helicobacter pylori is a class I carcinogen. Nowadays, the problem of antibiotic resistance is increasing worldwide. The latest prevalence rates of infection and resistant status in Thailand vary or are out of date. Our aims are to identify the current prevalence and antibiotic resistance patterns in Thailand and to suggest regimens for treatment-naive and -resistant patients. METHODS: This descriptive retrospective study was conducted, using a urea breath test, on patients in King Chulalongkorn Memorial Hospital between 2013 and 2017. They were categorized into the diagnostic group and posttreatment group. Specimens from some patients were cultured to identify the antibiotic-resistant pattern. RESULTS: There were 1894 patients included in our study. The prevalence of H. pylori infection in dyspeptic patients was 28.4%. Of 1258 patients, 1165 (92.61%) responded to initial treatment. The 95 patients who failed to respond could respond to second-line treatment of longer period, at higher doses, or using other antibiotics (success rate 68.42%). There were 21.43, 14.29, and 10.71% of patients resistant to ciprofloxacin, metronidazole, and clarithromycin, respectively. However, no patients resistant to amoxicillin, tetracycline, and levofloxacin were found. CONCLUSION: The prevalence of H. pylori infection in Thailand has increased slightly. Initial regimens (triple therapy or sequential therapy or quadruple therapy) can be effective for the eradication of H. pylori infection, with a success rate of > 90%. For patients who failed to respond to initial triple therapy, using a longer duration of triple therapy or changing to quadruple therapy could be a good alternative. The resistance rates of amoxicillin, metronidazole, levofloxacin, and tetracycline are declining, but those of clarithromycin and ciprofloxacin are increasing.

Genistein Modulated Lipid Metabolism, Hepatic PPARγ, and Adiponectin Expression in Bilateral Ovariectomized Rats with Nonalcoholic Steatohepatitis (NASH).

The aim of this study was to evaluate the protective effects of genistein on lipid accumulation and apoptosis in estrogen deficient rats with NASH. Female Sprague-Dawley rats (n = 48) were divided into ovariectomized (OVX) and non-OVX groups. Each group was then sub-divided into 3 subgroups; control, NASH (rats fed with a high-fat, high-fructose (HFHF) diet), and NASH+Gen (rats fed with HFHF diet plus daily genistein at 16 mg/kg BW). Results showed that HFHF diet induced liver fat accumulation in both non-OVX and OVX rats, which was evidenced by hepatic steatosis on liver pathology and increased hepatic free fatty acid (FFA) and triglyceride levels. Hepatic fat accumulation was significantly more severe in NASH rats with OVX than non-OVX. Hepatocyte apoptosis was more severe in NASH groups compared with that in control groups. Genistein administration significantly improved histopathology of NASH in both non-OVX and OVX rats and attenuated hepatic lipid accumulation, oxidative stress, and hepatocyte apoptosis. Genistein also down-regulated PPARγ and up-regulated adiponectin expression. In summary, NASH could be worsened by estrogen deficiency, indicating the protective action of estrogen on NASH. Genistein administration alleviated hepatic steatosis and apoptosis through the down-regulation of PPARγ and up-regulation of adiponectin expression.

Effects of curcumin on oxidative stress, inflammation and apoptosis in L-arginine induced acute pancreatitis in mice.

BACKGROUND AND PURPOSE: Curcumin, an active constituent of rhizomes of Curcuma longa Linn, exhibits a variety of biological activities such as anti-inflammation and anti-oxidant. The present study aims to examine the effects of curcumin on oxidative stress, inflammation and apoptosis in L-arginine induced acute pancreatitis (AP) in mice. METHODS: Male ICR mice were randomly divided into 4 groups. Control group received intraperitoneal injection (i.p.) of 1% DMSO as a vehicle. AP group received two doses of i.p. L-arginine (L-Arg) 450 mg/100 g body weight (BW) at 1-hour interval. AP plus low-dose curcumin group received i.p. curcumin 50 mg/kg BW 1 hour before L-Arg injection and then once daily for 3 days. AP plus high-dose curcumin group received i.p. curcumin 200 mg/kg BW 1 hour before L-Arg injection and then once daily for 3 days. All mice were sacrificed at 72 hours. Pancreatic tissue was obtained for histological evaluation, immunohistochemical studies for nuclear factor-kappa beta (NF-kß), apoptosis and myeloperoxidase (MPO), and Western blot analyses for 4-Hydroxynonenal (4-HNE). Blood samples were collected for amylase analysis. RESULTS: Mean body weight was significantly lower in AP group than in control group, while in curcumin group, body weight was maintained. The serum amylase, number of MPO positive cells, NF-kB positive cells, TUNEL positive cells, and 4-HNE expression significantly increased in AP group when compared with control group, but decreased in low and high-dose curcumin groups. Mice in AP group developed severe pancreatic inflammation, edema and fat necrosis. While mice in low and high-dose curcumin groups showed a significant improvement in histopathological scores. There was no significant difference between low and high doses of curcumin. CONCLUSION: Curcumin could attenuate acute pancreatitis via anti-oxidant, anti-inflammation and anti-apoptosis property leading to the improvement in pancreatic damage.

Genistein-attenuated Gastric Injury on Indomethacin-induced Gastropathy in Rats.

OBJECTIVES: To investigates the mucoprotective effect of genistein on gastric injury in rats with indomethacin (IMN)-induced gastropathy. METHODS: Male Sprague-Dawley rats were randomly divided into three groups. Group 1 (control; n = 6) was given distilled water (DW). Group 2 (IMN; n = 6) was given indomethacin (IMN) 150 mg/kg dissolved in 5% sodium bicarbonate (NaHCO3-) 1 mL/rat via intragastric tube at time 0 and 4 h. Group 3 (genistein; n = 6) was given genistein 100 mg/kg dissolved in 0.1% dimethyl sulfoxide (DMSO) plus IMN 150 mg/kg at time described as group 2. Four hours after the second dose, the stomach was removed to examine iNOS western blot expression, malondialdehyde (MDA), and histopathologic examination. Serum was collected to determine TNF-alpha and prostaglandin E2 (PGE2) levels using ELISA technique. RESULTS: Tissue MDA and serum TNF-alpha were significantly increased in the IMN group, as compared to the control group (9.70 ± 0.40 vs. 1.56 ± 0.14 nmol/mg protein, P = 0.000; 210.28 ± 0.98 vs. 126.4 ± 0.13 pg/mL, P = 0.000, respectively) and decreased in the genistein group when compared to the IMN group (2.87 ± 0.37 vs. 9.70 ± 0.40 nmol/mg protein, P = 0.000; 156.59 ± 0.10 vs. 210.28 ± 0.98 pg/mL, P = 0.000, respectively). Serum PGE2 level in IMN group was decreased significantly compared with control group (152.83 ± 0.10 vs. 303.33 ± 2.16 pg/mL, P = 0.000) and increased in the genistein group compared to the IMN group (247.65 ± 0.01 vs. 152.83 ± 0.10 pg/mL, P = 0.000). Expression of tissue iNOS was increased in the IMN group and improved in genistein groups. Most of the rats in the IMN group developed moderate to severe gastric erosion and ulcers. Gastric erosions and neutrophil infiltration score were significantly decreased in the genistein group. CONCLUSIONS: Genistein attenuated IMN-induced gastropathy in rats by reducing inflammation, decreasing oxidative stress, restoring mucoprotective function, and improving gastric histopathology. SUMMARY: This is an experimental study of the effect of NSAIDs in gastropathy. This study demonstrated the efficacy of genistein in treatment of NSAIDs-induced gastropathy. Genistein efficacy is reflected in the attenuation of histological alterations, with improvement in key biological parameters involved in the pathogenesis of NSAIDs gastropathy. Abbreviations used: NSAIDs: Non-steroidal anti-inflammatory drugs; IMN: Indomethacin; COX: Cyclooxygenase; TNF: Tumor necrosis factor; ICAM: Intercellular adhesion molecule; iNOS: Inducible nitric oxide synthase; MDA: Malondialdehyde; CINC: Cytokine-induced neutrophil chemoattractant.