Effect of Sofosbuvir Plus Daclatasvir in Hepatitis C Virus Genotype-4 Patients: Promising Effect on Liver Fibrosis.

Background/purpose: The effect of sofosbuvir and daclatasvir in treatment of genotype 4 Hepatitis C Virus (HCV) is not well documented. This study investigated the safety and efficacy of sofosbuvir plus daclatasvir with or without ribavirin in treatment of HCV genotype 4 patients. The impact of therapy on liver fibrosis as well as the role of IL18 polymorphism in therapeutic outcome was assessed.

Inhibition of NF-κB/TNF-α pathway may be involved in the protective effect of resveratrol against cyclophosphamide-induced multi-organ toxicity.

Context: Cyclophosphamide (CyP), an efficient anticancer drug, may damage normal human cells. Resveratrol (RES), a natural polyphenol, has a diverse pharmacological properties.

Objective: To test possible protective effect of RES on multi-organ damage caused by CyP.

Protective mechanisms of resveratrol against methotrexate-induced renal damage may involve BCRP/ABCG2.

Resveratrol (RES) is a well-known polyphenol antioxidant. We have previously shown that testicular protective effect of RES against the anticancer drug methotrexate (MTX)-induced toxicity involves transporter-mediated mechanisms. Here, we investigated the effect of RES on MTX-induced nephrotoxicity.

Protective Mechanisms of Thymoquinone on Methotrexate-induced Intestinal Toxicity in Rats.

Background: Intestinal toxicity is a serious side effect in methotrexate (MTX) chemotherapy.

Objective: To investigate the mechanisms by which the anticancer drug MTX-induced intestinal damage could be prevented by thymoquinone (TQ), an active ingredient of Nigella sativa.

Materials And Methods: TQ was given orally for 10 days, and MTX toxicity was induced at the end of day 3 of the experiment, with or without TQ pretreatment.

Mechanisms of Thymoquinone Hepatorenal Protection in Methotrexate-Induced Toxicity in Rats.

To investigate mechanisms by which thymoquinone (TQ) can prevent methotrexate- (MTX-) induced hepatorenal toxicity, TQ (10 mg/kg) was administered orally for 10 days. In independent rat groups, MTX hepatorenal toxicity was induced via 20 mg/kg i.p.

Multi-drug resistance protein (Mrp) 3 may be involved in resveratrol protection against methotrexate-induced testicular damage.

Aims: To investigate the effect of resveratrol (RES) on methotrexate (MTX)-induced testicular damage.

Main Methods: RES (10mg/kg/day) was given for 8 days orally and MTX (20mg/kg i.p.

Peroxisome Proliferator Activator Receptor (PPAR)- γ Ligand, but Not PPAR- α , Ameliorates Cyclophosphamide-Induced Oxidative Stress and Inflammation in Rat Liver.

Hepatoprotective potential of peroxisome proliferator activator receptor (PPAR)- α and - γ agonists, fenofibrate (FEN), and pioglitazone (PIO), respectively, against cyclophosphamide (CP)-induced toxicity has been investigated in rat. FEN and PIO (150 and 10 mg/kg/day, resp.) were given orally for 4 weeks.

Mechanism of testicular protection of carvedilol in streptozotocin-induced diabetic rats.

Aims: Male sub-fertility and infertility are major complications of diabetes mellitus. The non-selective β-blocker carvedilol has been reported to have favorable effects on some of the diabetic complications based on its antioxidant and anti-apoptotic effects. This study aims to evaluate the possible testicular protective effect of carvedilol in streptozotocin (STZ)-induced diabetic rat model and its possible mechanisms.

Protective mechanisms of coenzyme-Q10 may involve up-regulation of testicular P-glycoprotein in doxorubicin-induced toxicity.

The anticancer drug; doxorubicin (DOX), causes testicular toxicity as an adverse effect. P-glycoprotein (P-gp) is a multidrug resistance efflux transporter expressed in blood-testis barrier, which extrudes DOX from the testis. We investigated whether DOX-induced gonadal injury could be prevented by the use of antioxidant; coenzyme-Q10 (CoQ10).

Protective effect of peroxisome proliferator activator receptor (PPAR)-α and -γ ligands against methotrexate-induced nephrotoxicity.

Context: The anticancer drug methotrexate (MTX) may cause multi-organ toxicities, including nephrotoxicity.

Objective: To investigate effects of peroxisome proliferator activator receptor (PPAR)-α and -γ agonists; fenofibrate (FEN) and pioglitazone (PIO), in MTX-induced nephrotoxicity in rats.

Methods: Rats were given FEN or PIO (150 or 5 mg/kg/day, respectively) orally for 15 days.

Renal glucuronidation and multidrug resistance protein 2-/ multidrug resistance protein 4-mediated efflux of mycophenolic acid: interaction with cyclosporine and tacrolimus.

Mycophenolic acid (MPA) is an immunosuppressant used in transplant rejection, often in combination with cyclosporine (CsA) and tacrolimus (Tac). The drug is cleared predominantly via the kidneys, and 95% of the administered dose appears in urine as 7-hydroxy mycophenolic acid glucuronide (MPAG). The current study was designed to unravel the renal excretory pathway of MPA and MPAG, and their potential drug-drug interactions.

Protective mechanisms of atorvastatin against doxorubicin-induced hepato-renal toxicity.

To investigate the mechanisms by which the anticancer drug doxorubicin (DOX)-induced hepato-renal damage could be prevented by the cholesterol-lowering statin, atorvastatin (Ator), Ator (10 mg/kg) was administered orally for 10 days, and, in independent rat groups, DOX hepato-renal toxicity was induced via a single i.p. dose of 15 mg/kg at day 5 of experiment, with or without Ator.

Interaction of immunosuppressive drugs with human organic anion transporter (OAT) 1 and OAT3, and multidrug resistance-associated protein (MRP) 2 and MRP4.

Renal proximal tubule transporters can play a key role in excretion, pharmacokinetic interactions, and toxicity of immunosuppressant drugs. Basolateral organic anion transporters (OATs) and apical multidrug resistance-associated proteins (MRPs) contribute to the active tubular uptake and urinary efflux of these drugs, respectively. We studied the interaction of 12 immunosuppressants with OAT1- and OAT3-mediated [(3)H]-methotrexate (MTX) uptake in cells, and adenosine triphosphate-dependent [(3)H]-MTX transport in membrane vesicles isolated from human embryonic kidney 293 cells overexpressing human MRP2 and MRP4.

Lectin-like oxidized low-density lipoprotein receptor 1 pathways.

Background: The role of lectin-like oxidized low-density lipoprotein receptor (LOX)-1 has been implicated in the pathogenesis of different diseases, including atherosclerosis, hypertension, obesity, diabetes mellitus and metabolic syndrome. To date, several studies aimed at partially investigating the mechanistic role of LOX-1 in these various pathologies. Still, so far, the precise signal transduction pathways involving LOX-1 have not yet been elucidated.

Effect of coenzyme-q10 on Doxorubicin-induced nephrotoxicity in rats.

Nephrotoxicity is one of the limiting factors for using doxorubicin (Dox) as an anticancer chemotherapeutic. Here, we investigated possible protective effect of coenzyme-Q10 (CoQ10) on Dox-induced nephrotoxicity and the mechanisms involved. Two doses (10 and 100 mg/kg) of CoQ10 were administered orally to rats for 8 days, in the presence or absence of nephrotoxicity induced by a single intraperitoneal injection of Dox (15 mg/kg) at day 4 of the experiment.

Functional role of arginine 375 in transmembrane helix 6 of multidrug resistance protein 4 (MRP4/ABCC4).

Multidrug resistance protein (MRP) 4 transports a variety of endogenous and xenobiotic organic anions. MRP4 is widely expressed in the body and specifically localized to the renal apical proximal tubule cell membrane, where it mediates the excretion of these compounds into urine. To characterize the MRP4 substrate-binding site, the amino acids Phe368, Phe369, Glu374, Arg375, and Glu378 of transmembrane helix 6, and Arg998 of helix 12, localized in the intracellular half of the central pore, were mutated into the corresponding amino acids of MRP1 and MRP2.

Mechanisms of renal anionic drug transport.

By utilizing filtration, active secretion and reabsorption processes, the kidney can conserve essential nutrients, and eliminate drugs and potentially toxic compounds. Active uptake of organic anions and cations across the basolateral membrane, and their extrusion into the urine across the brush border membrane mainly takes place in the renal proximal tubule cells, and is facilitated via a range of substrate-specific tubular transporters. Many drugs and their phase II conjugates are anionic compounds, and therefore renal organic anion transporters are important determinants of their distribution and elimination.

Interaction of nonsteroidal anti-inflammatory drugs with multidrug resistance protein (MRP) 2/ABCC2- and MRP4/ABCC4-mediated methotrexate transport.

Methotrexate (MTX) has been used in combination with nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of inflammatory diseases as well as malignancies. Especially at high MTX dosages, severe adverse effects with this combination may occur, usually resulting from an impaired renal elimination. It has been shown that the mechanism of this interaction cannot be fully attributed to inhibition of basolateral MTX uptake in renal proximal tubules.