At indicated dosage, PPAR-γ ligand; PIO shows better improvement of MTX-induced nephrotoxicity compared to PPAR-α ligand; FEN due to differential effect on TNF-α/NF-κB inflammatory pathway.

Methotrexate (MTX) is a widely used chemotherapeutic agent but its clinical use is challenged with different forms of toxicities including testicular injury. The aim of the current study was to evaluate the potential protective effect of potassium channel opener, nicorandil (NIC) (3 and 10 mg/kg/day) on MTX-induced testicular injury in a rat model. Rats were randomly divided into four groups (nine rats each) and treated for 2 weeks as follows: (I) normal control (CON group) received vehicle, (II) model group (MTX group) given MTX (20 mg/kg) single intraperitoneal ( i.p.) injection dose on 11th day, (III) MTX + NLD group treated with NIC (3 mg/kg/day) orally for 2 weeks and MTX (20 mg/kg) single i.p. dose on 11th day, and (IV) MTX + NHD group treated with NIC (10 mg/kg/day) orally for 2 weeks and MTX (20 mg/kg) single i.p. injection on the 11th day. The testicular injury was assessed biochemically via serum testosterone, total antioxidant capacity, testicular oxidative stress parameters, P-glycoprotein, tumor necrosis factor-alpha, and interleukin-1β. Furthermore, histopathological evaluation, endothelial nitric oxide synthase (eNOS) immunoexpression, and detection of p53 expression level using Western blotting were performed. Results showed that MTX induced testicular injury which was proved by both biochemical and histopathological evaluations. Our results concluded that NIC pretreatment attenuated MTX-induced testicular injury via significantly increased eNOS immunoexpression, antiapoptotic, anti-inflammatory, and antioxidant properties. Interestingly, NIC high dose is more protective than low dose.

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Retinopathy associated with interferon α-2a and ribavirin combination therapy tends to develop in patients of older age with hypertension and diabetes.

Background/Aim:Recently, endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) has emerged using a self-expandable metallic stent (SEMS). The aim of the study was to evaluate the long-term outcomes of this procedure. In addition, the efficacy and safety of EUS-GBD with SEMS were assessed.Patients and Methods:Thirteen consecutive patients who underwent EUS-GBD for acute cholecystitis between February 2014 and September 2016 were included in this retrospective study. EUS-GBD was performed under the guidance of EUS and fluoroscopy, through puncturing the gallbladder with a needle, inserting a guidewire, dilating the puncture hole, and placing a SEMS.Results:The rates of technical success, functional success, and adverse events were 100%, 92.3% and 7.7%, respectively. The median procedure time was 26.9 min (range 19–42 min). The median follow-up time was 240 days (range 14–945 days) and during this follow-up period recurrence of cholecystitis was observed in one patient (7.7%).Conclusion:EUS-GBD with a SEMS is a possible alternative treatment for acute cholecystitis in high surgical risk patients. Long-term outcomes after EUS-GBD were promising.

Aim of the studyNon-alcoholic fatty liver disease (NAFLD) is a challenging health problem. Hyperuricemia is a key player in the pathogenesis of NAFLD. This study investigated the effect of allopurinol (uric acid synthesis inhibitor) in combination with metformin and vitamin E in prevention of fructose induced-fatty liver in rats.Material and methodsRats were divided into 7 groups: control group, fructose group (model group of NAFLD), allopurinol-treated group, metformin-treated group, vitamin E-treated group, metformin plus vitamin E-treated group and a combination group (received allopurinol plus metformin plus vitamin E). Development of NAFLD was assessed biochemically by serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as well as by histopathological examination. Oxidative stress parameters [reduced glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA)], and the inflammatory mediators tumor necrosis factor α (TNF-α) and inducible nitric oxide synthase (iNOS) were assessed, along with serum levels of uric acid and triglyceride (TG).ResultsCombination of allopurinol plus metformin plus vitamin E significantly attenuated fatty changes compared to their respective monotherapy. Interestingly, though all treated groups showed significant attenuation in the oxidative stress markers, TNF-α level and iNOS immunostaining in hepatic tissue, along with a significant decrease in the levels of uric acid and TG, the combination group showed a further significant decrease in the serum level of uric acid and iNOS immunostaining compared to other treated regimens.ConclusionsAllopurinol synergistically increases the protective effect of metformin and vitamin E in treatment of NAFLD, namely via reduction of uric acid synthesis and iNOS expression.

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