Drug and Alcohol Rehabilitation: Murine Atrial HL-1 Cell Line Is a Reliable Model to Study Drug Metabolizing Enzymes in the Heart.

Murine Atrial HL-1 Cell Line is a Reliable Model to Study Drug Metabolizing Enzymes in the Heart.

Filed under: Drug and Alcohol Rehabilitation

Vascul Pharmacol. 2012 Dec 22;
Elshenawy OH, Anwar-Mohamed A, Abdelhamid G, El-Kadi AO

HL-1 cells are currently the only cells that spontaneously contract while maintaining a differentiated cardiac phenotype. Thus, our objective was to examine murine HL-1 cells as a new in vitro model to study drug metabolizing enzymes. We examined the expression of cytochrome P450s (Cyps), phase II enzymes, and nuclear receptors and compared their levels to mice hearts. Our results demonstrated that except for Cyp4a12 and Cyp4a14 all Cyps, phase II enzymes: glutathione-S-transferases (Gsts), heme oxygenase-1 (HO-1), and NAD(P)H: quinone oxidoreductase (Nqo1), nuclear receptors: aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), pregnane X receptor (PXR), and peroxisome proliferator activated receptor (PPAR-alpha) were all constitutively expressed in HL-1 cells. Cyp2b19, Cyp2c29, Cyp2c38, Cyp2c40, and Cyp4f16 mRNA levels were higher in HL-1 cells compared to mice hearts. Cyp2b9, Cyp2c44, Cyp2j9, Cyp2j11, Cyp2j13, Cyp4f13, Cyp4f15 mRNA levels were expressed to the same extent to that of mice hearts. Cyp1a1, Cyp1a2, Cyp1b1, Cyp2b10, Cyp2d10, Cyp2d22, Cyp2e1, Cyp2j5, Cyp2j6, Cyp3a11, Cyp4a10, and Cyp4f18 mRNA levels were lower in HL-1 cells compared to mice hearts. Moreover, 3-methylcholanthrene induced Cyp1a1 while fenofibrate induced Cyp2j9 and Cyp4f13 mRNA levels in HL-1 cells. Examining the metabolism of arachidonic acid (AA) by HL-1 cells, our results demonstrated that HL-1 cells metabolize AA to epoxyeicosatrienoic acids, dihydroxyeicosatrienoic acids, and 20-hydroxyeicosatetraenoic acids. In conclusion, HL-1 cells provide a valuable in vitro model to study the role of Cyps and their associated AA metabolites in addition to phase II enzymes in cardiovascular disease states.
HubMed – drug


Acute Withdrawal but not Long-Term Withdrawal from Methamphetamine Affects Sexual Behavior in Female Rats.

Filed under: Drug and Alcohol Rehabilitation

Pharmacol Biochem Behav. 2012 Dec 22;
Thibodeau RB, Ornelas LC, Romero J, Memos N, Scheible M, Avila A, Schumacher A, Navarro A, Zimmermann K, Cuenod BA, Frohardt RJ, Guarraci FA

The present study was designed to investigate the long-term effects of repeated methamphetamine (MA) exposure on sexual motivation in female rats tested after a period of drug abstinence. In Experiment 1, female subjects received three injections of MA (1.0 mg/kg/day, every other day) or saline and were tested for paced mating behavior (where females could control the receipt of sexual stimulation from one male rat) 21 days after their last injection. In Experiment 2, female subjects received 12 consecutive injections of MA (1.0 mg/kg/day) or saline and were tested for mate choice (where females could control the receipt of sexual stimulation from two male rats simultaneously) 6 days after their last injection. Experiment 3 was identical to Experiment 2 except that female subjects received no baseline mating test and were tested for mate choice 24 hr and 6 days after their last injection. Open field tests were conducted in each experiment to measure locomotor activity after repeated exposure to MA. Although repeated MA exposure increased locomotor activity, mating behavior was not facilitated after either a short (6 days) or long (21 days) period of drug abstinence. Nevertheless, sexual behavior was disrupted during the 24 hr acute withdrawal period. Therefore, although the present study found no evidence of cross-sensitization between female sexual behavior and MA after either a short or a long period of drug abstinence, sexual behavior in sexually naïve female rats is sensitive to the depressive state associated with acute withdrawal from MA. In conclusion, the results of the present study suggest that MA acts differently from other psychomotor stimulants, and that the effects of MA withdrawal on sexual behavior differ between male and female rats.
HubMed – drug


Nanoparticles accumulate in ischemic core and penumbra region even when cerebral perfusion is reduced.

Filed under: Drug and Alcohol Rehabilitation

Biochem Biophys Res Commun. 2012 Dec 22;
Ishii T, Fukuta T, Agato Y, Oyama D, Yasuda N, Shimizu K, Kawaguchi AT, Asai T, Oku N

The use of a liposomal drug delivery system is a promising strategy for avoiding side effects and enhancing drug efficiency by changing the distribution of the intact drug. We have previously shown that liposomal agents quickly accumulated in an ischemia-reperfusion region and ameliorated cerebral ischemia-reperfusion injury when they were injected after reperfusion in transient middle cerebral artery occlusion (t-MCAO) rats. In the present study, we hypothesized that liposomes also act effectively as a drug carrier in the ischemic state, since the integrity of the blood brain barrier is disrupted at an early stage after an ischemic event. To test this hypothesis, the cerebral distribution of fluorescence-labeled liposomes was observed in permanent MCAO (p-MCAO) rats. The liposomes accumulated in the ischemic core and the penumbra region when injected at 1 or 2 h after occlusion. The accumulation in the ischemic core region was clearly greater than that in the penumbra region, despite the cerebral blood perfusion of the core region being substantially reduced. This result suggests that drug delivery to an ischemic region using liposomes is possible even when cerebral blood circulation has not recovered. Because liposomal drug delivery systems have the potential to effectively employ a number of agents that have failed in clinical trials, they may offer an effective strategy for achieving neuroprotection in stroke patients.
HubMed – drug


[Aging and Bio-motor function. Current approach to osteoporosis].

Filed under: Drug and Alcohol Rehabilitation

Clin Calcium. 2013 Jan; 23(1): 75-82
Hosoi T

The aim of prevention and treatment of osteoporosis is to prevent osteoporotic fractures. In the process of revising the Japanese guideline for prevention and treatment of osteoporosis and the diagnostic criteria of primary osteoporosis, the clinical significance of prevalent fragile fractures was re-considered. Recent advances in the development of the drugs for osteoporosis should be followed by the new evidences, for example about appropriate selection of the drug and duration of drug therapy. Advices to collect life style are important for the effective drug therapy as well as for the prevention of osteoporosis.
HubMed – drug


[A new photodynamic therapy drug toward gastric cancer MGC803 cell].

Filed under: Drug and Alcohol Rehabilitation

Zhonghua Wei Chang Wai Ke Za Zhi. 2012 Dec; 15(12): 1291-5
Chen JJ, Wei W, Ji AF, Liu TJ

To investigate the treatment efficiency of a new photodynamic therapeutic(PDT) drug synthesized by our laboratory toward MGC803 cells and related mechanisms.Bleaching method was used to evaluate the photostability of drug upon repetitive illumination. MTT assay was used to determine the ability of new drug killing MGC803 cells after PDT. Laser scanning confocal microscopy (LSCM) was applied to investigate the subcellular localization of drug in MGC803 cells (mitochondria and/or lysosomes). Hoechst staining and flow cytometry(Annexin V/PI double-staining) were performed to detect the death mode of MGC803 cells after PDT.This new PDT drug had good stability to light irradiation after repetitive illumination. MTT assay showed no cytotoxicity towards MGC803 cells only by drug or only by irradiation(P>0.05), but intense lethal effect was observed with drug and light combination(P<0.05). The phototoxicity of medicine increased with the elevation of concentration, the LD50 was 1.74 ?mol/L, and reaching plateau at the concentration of 3.12 ?mol/L, even increasing the concentration. LSCM found that drug localized in lysosomes of MGC803 cells. Hoechst staining showed that the death mode of cells was mainly necrosis and Annexin V/PI double-staining proved this result further.This new PDT drug is an effective PDT sensitizer for MGC803 cells and the death mode of cells is mainly necrosis. HubMed – drug



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