Topical delivery of doxepin using liposome containing cream: An emerging approach in enhancing skin retention.

Conventional formulation of topical doxepin has similar antihistaminic effects as oral doxepin; however, its efficacy is limited due to poor localized effects on the skin. This study was designed to compare the ex vivo permeation and retention of two topical doxepin formulations; liposomal cream and plain cream. Doxepin-containing liposomes were prepared with the thin-film hydration method and assessed for size, size distribution, morphology, entrapment efficiency (EE%) and stability Using rat skin specimens in a Franz diffusion cell. Doxepin concentration in skin and receptor fluid was quantified by a validated HPLC method. The optimized liposomal formulation represented a uniform shape with narrow size distribution and an average diameter of 208.7±5.6nm. EE% of doxepin was 79±1.3 and the liposomes were stable at least for six weeks at 4°C. Ex vivo studies showed that while a significantly higher amount of doxepin has passed through the skin and entered the receptor compartment from conventional dosage form (47.06±2.5µg/cm2vs 11.20±0.6µg/cm2 for liposomal formulation), liposomal doxepin favoured accumulation in dermis and epidermis. These results suggest that the liposomal doxepin cream is an effective and easy-to-use formulation and may improve the cutaneous retention of doxepin, thus decreasing its systemic side effects.

Linalool reverses benzene-induced cytotoxicity, oxidative stress and lysosomal/mitochondrial damages in human lymphocytes.

Benzene exposure results in bone marrow suppression, leading to a decrease in the number of circulating white blood cells, an increased risk of chronic lymphocytic leukemia, acute myeloid leukemia and aplastic anemia. Since the mechanism of induction of benzene toxicity is due to active metabolites through cytochrome p450 enzymes and production of reactive oxygen species (ROS), we hypothesized that natural compound such linalool with anti-inflammatory/antioxidant properties could be effective in reducing its toxicity. Lymphocytes isolated from healthy individuals were simultaneously cotreated with different concentrations of LIN (10, 25 and 50 µM) and benzene (50 µM) for 4 h at 37 °C. After incubation, the toxicity parameters such cytotoxicity, ROS formation, lysosomal membrane integrity, mitochondria membrane potential (ΔΨm) collapse, oxidized/reduced glutathione (GSH/GSSG) and malondialdehyde (MDA) were analyzed using biochemical and flow cytometry evaluations. Our data showed that benzene (50 µM) induced a significant increase in cytotoxicity, ROS formation, mitochondrial membrane potential (MMP) collapse, lipid peroxidation and oxidative stress while LIN with antioxidant potential reversed the toxic effects of benzene on isolated human lymphocytes. Our results suggest that LIN reduces and reverses benzene-induced cytotoxicity, oxidative stress and lysosomal/mitochondrial damages in human lymphocyte. This study demonstrated that cotreatment of LIN with benzene can reduce several parameters indicative of oxidative stress. As such, LIN could represent a potential therapeutic agent in reducing certain aspects of benzene-induced toxicity.

Synthesis and cytotoxic effect of a few N-heteroaryl enamino amides and dihydropyrimidinethiones on AGS and MCF-7 human cancer cell lines.

BACKGROUND AND PURPOSE: Cancer prevalence has increased in the last century posing psychological, social, and economic consequences. Chemotherapy uses chemical molecules to control cancer. New studies have shown that dihydropyrimidinethione (DHPMT) derivatives have the potential of being developed into anticancer agents. EXPERIMENTAL APPROACH: New derivatives of DHPMTs and a few acyclic bioisosters were synthesized via Biginelli reaction and assessed for their toxicity against gastric (AGS) and breast cancer (MCF-7) cell lines through MTT method. FINDINGS / RESULTS: Chemical structures of all synthesized N-heteroaryl enamino amides and DHPMTs were confirmed by spectroscopic methods. Result of biological assessment exhibited that none of the tested agents was more cytotoxic than cis-platin against AGS and MCF-7 cell lines and compound 2b was the most cytotoxic agent against AGS (IC50 41.10 µM) and MCF-7 (IC50 75.69 µM). Cytotoxic data were mostly correlated with the number of H-bond donors within gastric and breast cancer cells. CONCLUSION AND IMPLICATIONS: It was realized that DHPMTs were able to inhibit the growth of cancer cells much better than acyclic enamino amides and moreover; N-(4-methylbenzothiazol-2-yl) DHPMT derivative (2b) supposed possible interaction with a poor electron site of target due to the lipophilic nature of benzothiazole ring and also less electron rich nature than isoxazole. Similar scenario was observed with acyclic enamino amides in which incorporation of sulfur and nitrogen containing heterocycles doubled the cytotoxic effects. Results of the present contribution might assist in extending the scope of DHPMTs as privileged medicinal scaffolds.

Synthesis and cytotoxicity evaluation of novel cyclic/non-cyclic N-aryl enamino amides against human cancer cell lines.

BACKGROUND AND PURPOSE: Considering the undesirable consequences of prevalent cancer diseases, design and development of potent and selective anticancer chemotherapeutics is a major concern. Several studies have unraveled the potential of dihydropyrimidinone (DHPM) scaffold toward generating anticancer agents. EXPERIMENTAL APPROACH: In the present work, a series of new dihydropyrimidinethiones (DHPMTs) along with a few acyclic enamino amides were synthesized and evaluated for their cytotoxic activity against human gastric (AGS), liver (Hep-G2), and breast (MCF-7) cancer cell lines. FINDINGS/RESULTS: Among the assessed compounds, one of the DHPMT derivatives (compounds, one of the DHPMT derivatives (compound 5: 4-(3- fluorophenyl)-6-methyl-N-phenyl-2-thioxo-1,2,3,4-ttrahydropyrimidine-5-carboxamide) exhibited superior cytotoxicity in all of the target cell lines (AGS, IC50 9.9 µM; MCF-7, IC50 15.2 µM; and Hep-G2, IC50 40.5 µM). Cytotoxicity assessments showed that non-cyclic enamino amides exhibited weaker activities when compared to cyclic analogues (DHPMs). CONCLUSION AND IMPLICATIONS: DHPMTs were better cytotoxic agents than non-cyclic enamino amides. Structure activity relationship studies guided us toward the design of DHPMT derivatives with OH and NH groups particularly on meta position of 4-phenyl ring and hydrophobic bulky substituents on carboxamide side chain within the structure. Possible interaction with the hydrophobic site(s) of the cellular target was supposed. The results of this study emphasized the potential role of DHPMTs and their optimized derivatives as privileged medicinal scaffolds to inhibit the growth of gastric, breast, and liver cancer cells.

Magnesium sulfate protects blood-brain barrier integrity and reduces brain edema after acute ischemic stroke in rats.

Brain edema is a fatal complication of acute ischemic stroke and associated with worse outcomes in patients. This study was designed to evaluate the effects of magnesium sulfate on vasogenic brain edema formation and blood-brain barrier (BBB) disruption caused by ischemia-reperfusion (IR) in a rat model of ischemic stroke. A total of 72 male Sprague-Dawley rats were categorized into the following three primary groups: sham, control ischemic, magnesium-sulfate-treated (300 mg/kg loading dose, followed by an additional 100 mg/kg) ischemic (n = 24 in each group). Transient focal cerebral ischemia was induced by 60-min-long occlusion of the left middle cerebral artery, followed by 24-h-long reperfusion. Sensorimotor deficits, infarct volume, and brain edema were evaluated at the end of the reperfusion period. The BBB permeability was assessed by Evans Blue extravasation technique. Lipid peroxidation levels were assessed by measuring the malondialdehyde content in the brain tissue homogenate, and the activities of the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase were detected according to the technical manual of the assay kits. Induction of cerebral ischemia in the control group produced considerable BBB damage in conjunction with severe brain edema formation. Treatment with magnesium sulfate significantly attenuated brain edema and protected BBB integrity in the ischemic lesioned hemisphere. In addition, magnesium sulfate reduced lipid peroxidation and increased antioxidant protection of brain tissue by upregulating the activities of antioxidant enzymes. Treatment with magnesium sulfate protected BBB integrity against IR-induced damage and reduced vasogenic edema formation partly via antioxidant mechanisms in a rat model of acute ischemic stroke.

Cytokine Profile of Leishmania Infantum Fucose-Mannose Ligand in Vaccinated Dogs in the Northwest of Iran.

BACKGROUND: Canine visceral leishmaniasis (CVL) caused by Leishmania infantum is endemic in the northwest and south of Iran. An appropriate vaccine can help to prevent and control visceral leishmaniasis in both humans and animals. Few studies have confirmed that the fucose-mannose ligand (FML) antigen of Leishmania donovani produced protective immunity in dogs against CVL. OBJECTIVE: To evaluate the immune responses of vaccinated dogs against FML antigen of L. infantum. METHODS: We isolated the FML antigen from native L. infantum and vaccinated the dogs with FML-saponin in an endemic area of VL in Iran to evaluate the immune responses of vaccinated dogs against this antigen. RESULTS: Our results indicated a significant increase in the expression of IFN-γ, IL-10 and IL-13, but not IL-12A, gene transcripts in PBMCs of FML-saponin vaccinated dogs in comparison with controls. Our findings showed a significant difference in the ratio of IFN-γ/IL-10 mRNA expression in FML-saponin vaccinated dogs in comparison with two control groups. Moreover, a significant level of anti-FML antibodies was detected in serum of vaccinated dogs. CONCLUSION: These findings showed that FML-saponin stimulates both Th1 and Th2 immune responses with predominant Th1 and strong humoral immune responses to produce protective immunity against CVL.

Fe(3)O(4)/polyethylene glycol nanocomposite as a solid-phase microextraction fiber coating for the determination of some volatile organic compounds in water.

A high-performance metal oxide polymer magnetite/polyethylene glycol nanocomposite was prepared and coated in situ on the surface of the optical fiber by sol-gel technology. The magnetite nanoparticles as nanofillers were synthesized by a coprecipitation method and bonded with polyethylene glycol as a polymer. The chemically bonded coating was evaluated for the headspace solid-phase microextraction of some environmentally important volatile organic compounds from aqueous samples in combination with gas chromatography and mass spectrometry. The prepared fiber was characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. The mass ratio of nanofiller and polymer on the coating extraction efficiency, morphology, and stability were investigated. The parameters affecting the extraction efficiency, including the extraction time and temperature, the ionic strength, desorption temperature, and time were optimized. The sol-gelized fiber showed excellent chemical stability and longer lifespan. It also exhibited high extraction efficiency compared to the two types of commercial fibers. For volatile organic compounds analysis, the new fiber showed low detection limits (0.008-0.063 ng/L) and wide linearity (0.001-450 × 104 ng/L) under the optimized conditions. The repeatability (interday and intraday) and reproducibility were 4.13-10.08 and 5.98-11.61%, and 7.35-14.79%, respectively (n = 5). For real sample analysis, three types of water samples (ground, surface, and tap water) were studied.

An innovative method for analysis of Pb (II) in rice, milk and water samples based on TiO2 reinforced caprylic acid hollow fiber solid/liquid phase microextraction.

In the present study, nano-sized titanium oxides were applied for preconcentration and determination of Pb(II) in aqueous samples using hollow fiber based solid-liquid phase microextraction (HF-SLPME) combined with flame atomic absorption spectrometry (FAAS). In this work, the nanoparticles dispersed in caprylic acid as an extraction solvent was placed into a polypropylene porous hollow fiber segment supported by capillary forces and sonification. This membrane was in direct contact with solutions containing Pb (II). The effect of experimental conditions on the extraction, such as pH, stirring rate, sample volume, and extraction time were optimized. Under the optimal conditions, the performance of the proposed method was investigated for the determination of Pb (II) in food and water samples. The method was linear in the range of 0.6-3000µgmL-1. The relative standard deviations and relative recovery of Pb (II) was 4.9% and 99.3%, respectively (n=5).

Alpha-Tocopherol Reduces Brain Edema and Protects Blood-Brain Barrier Integrity following Focal Cerebral Ischemia in Rats.

OBJECTIVE: This study was conducted to examine the neuroprotective effects of α-tocopherol against edema formation and disruption of the blood-brain barrier (BBB) following transient focal cerebral ischemia in rats. MATERIALS AND METHODS: Ninety-six male Sprague-Dawley rats were divided into 3 major groups (n = 32 in each), namely the sham, and control and α-tocopherol-treated (30 mg/kg) ischemic groups. Transient focal cerebral ischemia (90 min) was induced by occlusion of the left middle cerebral artery. At the end of the 24-hour reperfusion period, the animals were randomly selected and used for 4 investigations (n = 8) in each of the 3 main groups: (a) assessment of neurological score and measurement of infarct size, (b) detection of brain edema formation by the wet/dry method, (c) evaluation of BBB permeability using the Evans blue (EB) extravasation technique, and (d) assessment of the malondialdehyde (MDA) and reduced glutathione (GSH) concentrations using high-performance liquid chromatography methods. RESULTS: Induction of cerebral ischemia in the control group produced extensive brain edema (brain water content 83.8 ± 0.11%) and EB leakage into brain parenchyma (14.58 ± 1.29 µg/g) in conjunction with reduced GSH and elevated MDA levels (5.86 ± 0.31 mmol/mg and 63.57 ± 5.42 nmol/mg, respectively). Treatment with α-tocopherol significantly lowered brain edema formation and reduced EB leakage compared with the control group (p < 0.001, 80.1 ± 0.32% and 6.66 ± 0.87 µg/g, respectively). Meanwhile, treatment with α-tocopherol retained tissue GSH levels and led to a lower MDA level (p < 0.01, 10.17 ± 0.83 mmol/mg, and p < 0.001, 26.84 ± 4.79 nmol/mg, respectively). CONCLUSION: Treatment with α-tocopherol reduced ischemic edema formation and produced protective effects on BBB function following ischemic stroke occurrence. This effect could be through increasing antioxidant activity.

Effect of virgin olive oil versus piroxicam phonophoresis on exercise-induced anterior knee pain.

OBJECTIVE: The main purpose of this study was to evaluate the effects of virgin olive oil phonophoresis on female athletes' anterior knee pain (AKP). MATERIALS AND METHODS: A double blinded randomized clinical trial was conducted. Ninety-three female athletes suffering from AKP voluntarily participated in this study. Patients were randomly assigned into olive oil (n=31), piroxicam (n=31) or base gel phonophoresis (n=31) groups. At the baseline visit, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire was filled by subjects who were then treated with olive oil, piroxicam or pure phonophoresis for 12 sessions. After 6 and 12 sessions of physiotherapy, subjects filled the questionnaire again. Main outcomes were significant improvement in pain, stiffness, physical function, and total WOMAC scores. RESULTS: Although, there was a significant reduction in symptoms of AKP at the end of the therapy in all groups (p<0.05), but in olive oil group, this improvement was seen after 6 sessions of treatment (p<0.001). A significant difference between olive oil group and piroxicam and/or phonophoresis group was observed after 6 sessions of therapy (p<0.05). CONCLUSION: It could be proposed that phonophoresis with virgin olive oil is as effective as piroxicam gel on lowering WOMAC scores of AKP in female athletes and also has several beneficial properties including faster effect and shorter duration of therapy. The exact mechanism of beneficial action of virgin olive oil on AKP is not clear and requires further studies.

Antioxidant Levels in Cord Blood of Term Neonates and Its Association with Birth Weight.

OBJECTIVE: Due to excessive production of free radicals and antioxidants evolved mechanisms against oxidative stress, infants are very vulnerable. As there was a significant relation between antioxidant levels and birth weight, we aimed verify this relationship. MATERIALS & METHODS: In this descriptive analytical study we evaluated the antioxidant status of 40 healthy term newborns (gestation age 38-42 wk) with weight >2500 g (AGA) and 40 healthy term newborns (gestation age 38-42 wk) with LBW babies (weight < 2500 g) (SGA) in Ardabil Buali Hospital, Ardabil, northwest Iran in 2014. About 15 Ml of cord blood was collected after the second stage of labor. The levels of vitamin A, E, and C, catalase, glutathione peroxidase (GPX), bilirubin and serum uric acid were measured by standard methods. Informed consent was obtained from newborn mothers and study protocol was approved by university Ethics Committee. Data were analyzed using SPSS.19. RESULTS: The mean levels of bilirubin, vitamin C, E, catalase and GPX in AGA group were significantly higher than SGA group but the mean of serum uric acid in SGA group was more than AGA. In addition, the mean of vitamin A was similar in two groups. There was a significant relation between antioxidant levels and birth weight in term newborns. CONCLUSION: In line with other studies the amounts of antioxidant levels except serum uric acid in AGA group was significantly more than SGA group.

Aqueous extract of Agrostemma githago seed inhibits caspase-3 and induces cell-cycle arrest at G1 phase in AGS cell line.

ETHNOPHARMACOLOGICAL RELEVANCE: A weed plant belonging to the Caryophyllaceae family, Agrostemma githago is used in folk medicine to treat cancers and warts. AIM OF THE STUDY: The aim of this study was to evaluate the cytotoxic effect of the aqueous extract of A. githago seed on gastric cancer cell line (AGS) and to investigate the mechanism of apoptosis induction in these cells. MATERIALS AND METHODS: Seeds of A. githago were collected from the suburban area of Ardabil Province, northwest Iran. After preparing the aqueous extract, dry matter was harvested with the lyophilizing technique. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to assess the cytotoxicity. Apoptotic cells were detected by staining with ethidium bromide/acridine orange (EB/AO). Diamidino-2-phenylindole (DAPI) staining was used for cell-cycle analysis with a flow cytometer. The annexin V binding level, caspase-3 activity, and B-cell lymphoma-2 (Bcl-2) level were also measured to confirm apoptotic cell death. RESULTS: After the aqueous extract of A. githago seed was incubated for 24, 48, and 72 h, inhibited cell growth was observed with IC50 values of 13.51 ± 0.7, 4.37 ± 1.01, and 2.42 ± 0.8 µg/ml, respectively. The EB/AO staining method demonstrated that the extract exerts its cytotoxic effect mainly via apoptosis, in accordance with the annexin V, blc-2, and caspase-3 results. The extract showed a concentration-dependent increase in annexin V binding to externally exposed phosphatidylserine as well as caspase-3 activity. The bcl-2 protein level showed a proportionate decrease with the increase in extract concentration. The cell-cycle analysis revealed that the extract can arrest cells at the G1 checkpoint. CONCLUSION: The findings of this study revealed the cytotoxic effect of the aqueous extract of A. githago seed on gastric cancer cells (AGS) mainly via apoptosis and the cell-cycle arrest at the G1 checkpoint. Therefore, the extract can be potentially used in gastric cancer therapy in vitro.

[PMIM]Br@TiO2 nanocomposite reinforced hollow fiber solid/liquid phase microextraction: an effective extraction technique for measurement of benzodiazepines in hair, urine and wastewater samples combined with high-performance liquid chromatography.

A new design of hollow fiber solid-liquid phase microextraction (HF-SLPME) was developed for the determination of benzodiazepines (BZPs) in hair, urine and wastewater. The membrane extraction with 1-pentyl-3-methylimidazolium bromide coated titanium dioxide ([PMIM]Br@TiO2) sorbent used in this research is a two-phase supported membrane extraction consisting of an aqueous (donor phase), and n-octanol/nano [PMIM]Br@TiO2 (acceptor phase) system operated in direct immersion sampling mode. The 1-pentyl-3-methylimidazolium bromide (ionic liquid) coated nano TiO2 dispersed in the organic solvent (n-octanol) is held into a porous membrane supported by capillary forces and sonification. It is in contact with the feed phase, which is the aqueous sample. The experimental setup is very simple and highly affordable. The hollow fiber is disposable, so single use of the fiber reduces the risk of cross-contamination and carry-over problems. The proposed method allows the very effective and enriched recuperation of BZPs into one single extract. In order to obtain high extraction efficiency of the analytes using this novel sorbent, the main parameters were optimized. Under the optimized extraction conditions, the method showed good linearity (0.05-6000ngmL(-1)), low limits of detection (0.08-0.5ngmL(-1)) and good enrichment (533-1190).

Overexpression of microRNA biogenesis machinery: Drosha, DGCR8 and Dicer in multiple sclerosis patients.

We aimed to evaluate the expression of the major components of microRNA biogenesis machinery including Drosha, Dicer and DiGeorge syndrome critical region gene 8 (DGCR8) in multiple sclerosis (MS) patients. The expression levels of these components in relapsing remitting multiple sclerosis (RRMS) patients were significantly up-regulated in comparison to healthy controls. DGCR8 was up-regulated 4.9 times in RRMS patients versus healthy controls, and Drosha was up-regulated 3.58 times. Additionally, the expression level of Dicer was 2.11 times higher in RRMS patients than the healthy controls. In conclusion, our results suggest that overexpression of Drosha, Dicer and DGCR8 may contribute to the pathogenesis of MS. Further investigation may introduce microRNA biogenesis machinery as MS markers and therapeutic targets.

Polyvinylimidazole/sol-gel composite as a novel solid-phase microextraction coating for the determination of halogenated benzenes from aqueous solutions.

A polyvinylimidazole/sol-gel composite is proposed as a novel solid-phase microextraction fiber to extract five halobenzenes from the headspace of aqueous solutions in combination with gas chromatography with mass spectrometry. The prepared fiber was characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. The obtained results showed that porous polyvinylimidazole/sol-gel composite was chemically deposited on fused silica fiber. The effect of important extraction parameters including extraction temperature, extraction time, and salt content were investigated. The optimum conditions were as follows: extraction temperature 25°C, extraction time 20 min, and salt concentration 30 w/v%. Detection limits and relative standard deviations of the developed method for halogenated benzenes were below 0.1 pg/mL and 15%, respectively. Repeatability of the proposed method, explained by relative standard deviation, varied between 5.48 and 9.15% (n = 5). The limits of detection (S/N = 3) ranged between 0.01 and 0.10 ng/L using gas chromatography with mass spectrometry with selected ion monitoring mode. For real sample analysis, three types of water samples with different matrices (ground, surface, and tap water) were studied. The optimized procedure was applied to extraction and method validation of halogenated benzenes in spiked water samples.

Enalapril attenuates ischaemic brain oedema and protects the blood-brain barrier in rats via an anti-oxidant action.

1. In the present study, we investigated the effects of postischaemic angiotensin-converting enzyme (ACE) inhibition with enalapril on vasogenic oedema formation and blood-brain barrier (BBB) integrity following transient focal cerebral ischaemia in rats. 2. Cerebral ischaemia was induced by 60 min occlusion of the right middle cerebral artery, followed by 24 h reperfusion. Vehicle and a non-hypotensive dose of enalapril (0.03 mg/kg) were administered at the beginning of the reperfusion period. A neurological deficit score (NDS) was determined for all rats at the end of the reperfusion period. Then, brain oedema formation was investigated using the wet-dry weight method and BBB permeability was evaluated on the basis of extravasation of Evans blue (EB) dye. In addition, oxidative stress was assessed by measuring reduced glutathione (GSH) and malondialdehyde (MDA) in brain homogenates. 3. Inhibition of ACE by enalapril significantly reduced NDS and decreased brain oedema formation (P < 0.05 for both). Disruption of the BBB following ischaemia resulted in considerable leakage of EB dye into the brain parenchyma of the ipsilateral hemispheres of vehicle-treated rats. Enalapril significantly (P < 0.05) decreased EB extravasation into the lesioned hemisphere. Enalapril also augmented anti-oxidant activity in ischaemic brain tissue by increasing GSH concentrations and significantly (P < 0.05) attenuating the increased MDA levels in response to ischaemia. 4. In conclusion, inhibition of ACE with a non-hypotensive dose of enalapril may protect BBB function and attenuate oedema formation via anti-oxidant actions.

Evaluation of Lipid-based Drug Delivery System (Phytosolve) on Oral Bioavailability of Dibudipine.

The objective of present study was to evaluate pharmacokinetic parameters of dibudipine Phytosolve after oral administration in rats. The solubility test was carried out to select suitable oily solvent for dibudipine. Phytosolve formulation was prepared with a medium chain triglyceride (MCT) oil (20%), soybean phospholipids (5%) and a 70% fructose solution (75%). The effect of polyol content on the mean globule size of Phytosolve formulation was studied. The optimized formulation was evaluated for robustness toward dilution, transparency, droplet size, zeta potential and transmission electron microscopic analysis. The Phytosolve of dibudipine with an average droplet size of 142.3 ± 4.3 nm and surface charge -18.36 ± 0.37 mv was administered orally to rats. The average relative bioavalabilities of dibudipine in the plasma with Phytosolve were 170.4% and 211.2% as compared to the oily solution and aqueous suspension respectively. So this formulation could be offered as a useful technique to improve the oral delivery of the poorly water soluble drugs such as dibudipine.

Effect of Methylsulfonylmethane Pretreatment on Aceta-minophen Induced Hepatotoxicity in Rats.

OBJECTIVE(S): Methylsulfonylmethane (MSM) is a sulfur-containing compound found in a wide range of human foods including fruits, vegetables, grains and beverages. In this study the effect of MSM pretreatment on acetaminophen induced liver damage was investigated. MATERIALS AND METHODS: Male Sprague Dawley rats were pretreated with 100 mg/kg MSM for one week. On day seven rats were received acetaminophen (850 mg/kg, intraperitoneal). Twenty-four hours later, blood samples were taken to determine serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Tissue samples of liver were also taken for the determination of the levels of malondialdehyde (MDA); total glutathione (GSH), superoxide dismutase (SOD), and myeloperoxidase (MPO) activity together with histopathological observations. RESULTS: High dose of acetaminophen administration caused a significant decrease in the GSH level of the liver tissue, which was accompanied with a decrease in SOD activity and increases in tissue MDA level and MPO activity. Serum ALT, AST levels were also found elevated in the acetaminophen-treated group. Pretreatment with MSM for one week was significantly attenuated all of these biochemical indices. CONCLUSION: Our findings suggest that MSM pretreatment could alleviate hepatic injury induced by acetaminophen intoxication, may be through its sulfur donating and antioxidant effects.

Expression levels of microRNA machinery components Drosha, Dicer and DGCR8 in human (AGS, HepG2, and KEYSE-30) cancer cell lines.

UNLABELLED: MicroRNAs (miRNAs) have recently been shown to play fundamental roles in diverse cellular processes and linked to variety of cancers. Dicer and Drosha are two major enzymes in the miRNA maturation process. DGCR8 is the assistant of Drosha in the microprocessor complex. In this study, we evaluated the mRNA expression profiles of major miRNA processing machinery Drosha, Dicer, and DGCR8 in human gastrointestinal (AGS, KYSE30 and HepG2) cancer cell lines. MATERIALS AND METHODS: The cells were cultured and harvested, and total cellular RNA was isolated from cells. Then, first-strand cDNA was synthesized from the RNA of cells. Afterward, Quantitative analysis was performed by real-time RT-PCR using the PowerSYBR Green PCR Master Mix. RESULTS: Expression levels of Drosha in AGS and HepG2 cells were higher than the controls, whereas, Drosha's expression level in KYSE-30 cell line was lower. The Dicer expression levels in AGS and HepG2 cells were higher, while, its expression level in KYSE-30 cell was lower. The DGCR8 expression levels in all three cell lines were significantly higher than the control samples. CONCLUSION: Expression levels of the two most important enzymes of the miRNA machinery, Drosha and Dicer, and microprocessor complex component, DGCR8 were noticeably dysregulated when compared to healthy controls.

Effect of methylsulfonylmethane on paraquat-induced acute lung and liver injury in mice.

Methylsulfonylmethane (MSM) is a natural organosulfur compound that exhibits antioxidative and anti-inflammatory effects. This study was carried out to investigate the effect of MSM on paraquat (PQ)-induced acute lung and liver injury in mice. A single dose of PQ (50 mg/kg, i.p.) induced acute lung and liver toxicity. Mice were treated with MSM (500 mg/kg/day, i.p.) for 5 days. At the end of the experiment, animals were euthanized, and lung and liver tissues were collected for histological and biochemical analysis. Tissue samples were used to determine malondialdehyde (MDA), myeloperoxidase (MPO), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), and tumor necrosis factor-α (TNF-α) levels. Blood samples were used to measure plasma alanine transaminase (ALT), γ-glutamyl transferase (GGT), and alkaline phosphatase (ALP). Histological examination indicated that MSM decreased lung and liver damage caused by PQ. Biochemical results showed that MSM treatment significantly reduced tissue levels of MDA, MPO, and TNF-α, while increased the levels of SOD, CAT, and GSH compared with PQ group. MSM treatment also significantly reduced plasma levels of ALT, GGT, and ALP. These findings suggest that MSM as a natural product attenuates PQ-induced pulmonary and hepatic oxidative injury.