The potential inhibitory effect of the antidiabetic and anti‐inflammatory drug, metformin on thioacetamide (TAA)‐induced hepatotoxicity associated with the inhibition of mammalian target of rapamycin (mTOR)–hypoxia‐inducible factor‐1α (HIF‐1α) axis has not been investigated before. Therefore, we tested whether metformin can protect against liver injuries including fibrosis induced by TAA possibly via the downregulation of mTOR–HIF‐1α axis and profibrogenic and inflammatory biomarkers. Rats either injected with TAA (200 mg/kg; twice a week for 8 weeks) before being killed after 10 weeks (model group) or were pretreated with metformin (200 mg/kg) daily for 2 weeks before TAA injections and continued receiving both agents until the end of the experiment, at Week 10 (protective group). Using light and electron microscopy examinations, we observed in the model group substantial damage to the hepatocytes and liver tissue such as collagen deposition, infiltration of inflammatory cells, and degenerative cellular changes with ballooned mitochondria that were substantially ameliorated by metformin. Metformin also significantly ( p < 0.05) inhibited TAA‐induced HIF‐1α, mTOR, the profibrogenic biomarker α‐smooth muscle actin, tissue inhibitor of metalloproteinases‐1, tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), alanine aminotransferase (ALT) and aspartate aminotransferase in harvested liver homogenates and blood samples. In addition, a significant ( p < 0.01) positive correlation between hypoxia scoring (HIF‐1α) and the serum levels of TNF‐α ( r = 0.797), IL‐6 ( r = 0.859), and ALT ( r = 0.760) was observed. We conclude that metformin protects against TAA‐induced hepatic injuries in rats, which is associated with the inhibition of mTOR–HIF‐1α axis and profibrogenic and inflammatory biomarkers; thus, may offer therapeutic potential in humans.
Between 1996 and 1997, we conducted a multicentre study to assess the effect of combination therapy of interferon (IFN) + ribavirin on chronic hepatitis C genotype 4. Ninety-seven patients were enrolled. Sixty-eight patients (47 male and 21 female) were non-responders to previous therapy with IFN (Group I). Twenty-nine patients (19 male and 10 female) were new (Group II). Following treatment with IFN, 23% in Group I and 9% in Group II had a sustained biochemical response. Only 12% in Group I and 5% in Group II achieved a sustained virological response. Virus load was found to be the major factor determining response, followed by histology grading and staging. Like HCV genotype 1, HCV genotype 4 seems to have a poor response to therapy.
Basidiobolomycosis is an unusual fungal infection known for dermatological manifestations that affect immunocompetent young adult and rarely involves the gastrointestinal tract, during the past decade many cases have been reported in Saudi Arabia with diagnosis of gastrointestinal basidiobolomycosis, most of the reported cases were in children and majority came from southern region of Saudi Arabia and all were misdiagnosed initially as either IBD or granulomatous diseases or malignancy. GIB poses diagnostic difficulties due to nonspecific presentations and rarity and has been scarcely reported in medical literatures. GIB might be a life threatening infection. So, a high index of suspicion is warranted in any child or young adult with differential diagnosis of IBD, granulomatous disease and malignancy affecting GI tract especially those patients whom are residents in or came from southern region of Saudi Arabia. In this series which is the largest reported series in adult patient with GIB in this country, we describe 4 cases of GI basidiobolomycosis from southern Region of Saudi Arabia.
We explored the possibility of the cryo-storage of cord blood hematopoietic stem cells (CBHPSC) with respect to the quantity, quality and biologic efficacy of high altitude (HA) region Abha against sea level (SL) region. The results of the post-processed total nucleated cell count was 8.03 ± 0.31 × 10 and 8.44 ± 0.23 × 10 cells in the HA and SL regions respectively. The mean post processing viability of the nucleated cells was about 87.03 ± 1.39 (HA) and 88.33 ± 1.55% (SL) while post thaw cells were 85.61 ± 1.44 (HA) and 86.58 ± 1.61% (SL) after transient cryo-storage. The proliferation of CBHSCs after thawing were comparable between the HA and SL regions. The results of the colony forming unit (CFU) assays of CFU-E, CFU-GEMM, CFU-GM and BFU-E were comparable between HA and SL in both fresh and post thaw, while a declining trend with viability was significant. The differentiation capability of post thaw samples into adipocytes and osteocytes were comparable between HA and SL regions. Overall from the results, it can be evidenced that HA cord blood collection, processing or storage does not hinder the quality or biological efficacy of the CBHPSC.
Potent heptatotoxic chemicals such as carbon tetrachloride and thioacetamide (TAA) are used to evaluate hepatoprotective agents. Here we sought to investigate the potential protective effect of the antidiabetic and antioxidant drug, metformin against liver injury induced by TAA. Model group rats received several injections of TAA (200 mg/kg) before being sacrificed after 10 weeks and the protective group started the treatment two weeks prior to TAA injections and continued receiving both agents, metformin and TAA until the end of the experiment, week 10. Harvested liver tissues were examined using light microscopy and liver homogenates were assayed for oxidative and anti-oxidative stress markers that are known to be modulated in liver injury. Profound damage in the hepatic tissue of the model group such as liver fibrosis and destruction of hepatic architectures were revealed, which were protected by metformin comparable to the control group. TAA augmented the oxidative stress biomarker, malondialdehyde (MDA) and ameliorated the antioxidant superoxide dismutase (SOD), which were significantly (p<0.05) protected by metformin treatment. These results indicate that metformin effectively protects against TAA-induced hepatotoxicity in a rat model.
We sought to determine whether the combined polyphenolic compounds, resveratrol and quercetin can substantially protect against modulation of hepatic biomarkers of apoptosis and survival, p53-Bax axis and B-cell lymphoma 2 (Bcl-2) in an animal model of acetaminophen-induced acute liver injury via the association of oxidative stress and interleukin-11 (IL-11). The model group of rats received a single dose of acetaminophen (2 g/kg), whereas the protective group of rats was pre-treated for 7 days with combined doses of resveratrol (30 mg/kg) and quercetin (50 mg/kg) before being given a single dose of acetaminophen. All rats were then sacrificed 24 hours post acetaminophen ingestion. Acetaminophen overdose induced acute liver injury as demonstrated by profound liver parenchymal damage and increased levels of the liver injury enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Acetaminophen significantly (p<0.05) modulated malondialdehyde (MDA), p53, apoptosis regulator Bax, Bcl-2, IL-11, interleukin-6 (IL-6), ALT, AST, superoxide dismutase (SOD), and glutathione peroxidase (GPx), which were significantly protected by resveratrol plus quercetin. We further demonstrated a significant (p<0.01) correlation between IL-11 scoring and the levels of p53, Bax, Bcl-2, and MDA. Thus, resveratrol plus quercetin effectively protect against acetaminophen-induced apoptosis, which is associated with the inhibition of oxidative stress and IL-11.
Introduction and objective: Chronic hepatitis C and B impose a significant mortality and morbidity burden worldwide and particularly in the Kingdom of Saudi Arabia (KSA). In haemodialysis patients (HD) patients, chronic hepatitis, especially HCV infection poses a real problem. The objective of this communication was to assess HCV and HBV infection rates in patients undergoing haemodialysis in Abha, Southern Saudi Arabia. Methods: In this cross-sectional hospital based study, we studied the demographic factors and the frequencies of HCV and HBV infection among all patients undergoing haemodialysis for end stage kidney disease in 2016. Those rates were compared to previous published reports. Results: There were 200 males and 118 females with ESRD undergoing haemodialysis. The prevalence of HCV infection was 10% among men and 18.6% among women (was 45%-68% in the year 2000). On the other hand, one male patient (0.5%) and 3 females (2.5%) were infected by both HCV and HBV. HBV infection was 5%-11% in the year 2000. Conclusion: The present study demonstrated a clear decline of both hepatitis C and B infection prevalence in a large haemodialysis facility as compared to a previous high infection rates a decade earlier. This decline is a result of strict application of the international guidelines and possible HBV vaccination programs.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.