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.

No abstract

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.

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.