The Journal of pharmacy and pharmacology
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J. Pharm. Pharmacol. · Aug 2008
ReviewMechanism of radiation-induced bystander effects: a unifying model.
The radiation-induced bystander effect represents a paradigm shift in our understanding of the radiobiological effects of ionizing radiation, in that extranuclear and extracellular events may also contribute to the final biological consequences of exposure to low doses of radiation. Although radiation-induced bystander effects have been well documented in a variety of biological systems, the mechanism is not known. It is likely that multiple pathways are involved in the bystander phenomenon, and different cell types respond differently to bystander signalling. ⋯ Inhibitors of nitric oxide (NO) synthase (NOS) and mitochondrial calcium uptake provided evidence that NO and calcium signalling are part of the signalling cascade. The bystander observations imply that the relevant target for various radiobiological endpoints is larger than an individual cell. A better understanding of the cellular and molecular mechanisms of the bystander phenomenon, together with evidence of their occurrence in-vivo, will allow us to formulate a more accurate model for assessing the health effects of low doses of ionizing radiation.
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J. Pharm. Pharmacol. · Aug 2008
ReviewAmelioration of the pathological changes induced by radiotherapy in normal tissues.
Damage to normal tissues remains the most important limiting factor in the treatment of cancer by radiotherapy. In order to deliver a radiation dose sufficient to eradicate a localised tumour, the normal tissues need to be protected. A number of pharmacological agents have been used experimentally, and some clinically, to alleviate radiation damage to normal tissues but at present there is no effective clinical treatment to protect normal tissues against radiation injury. ⋯ However, care must be taken in the administration of these substances for the management of different aspects of radiation damage because there appears to be a tissue-specific response to different pharmacological agents. Also, one must be aware of the limitations of results obtained from animal models, which do not necessarily correlate to benefits in the clinic; the conflicting results reported with some modifiers of radiation damage; and the toxicity of these substances and radiation doses used in published studies. Conflicting results may arise from differences in the pathophysiologic processes involved in the development of radiation lesions in different tissues, and in the markers used to assess the efficacy of treatment agents.
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J. Pharm. Pharmacol. · Oct 2007
Comparative StudyAntispasmodic activity of licochalcone A, a species-specific ingredient of Glycyrrhiza inflata roots.
Licochalcone A, a species-specific and characteristic retrochalcone ingredient of Glycyrrhiza inflata root, has been shown to possess multiple bioactive properties. However, its muscle relaxant activity has not been reported previously. ⋯ Furthermore, the IC50 (22.1 +/- 10.9 microM) of licochalcone A against cAMP PDE was similar to that of IBMX (26.2 +/- 7.4 microM). These results indicated that licochalcone A may have been responsible for the relaxant activity of G. inflata root and acted through the inhibition of cAMP PDE.
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J. Pharm. Pharmacol. · Aug 2007
Involvement of kappa opioid receptors in formalin-induced inhibition of analgesic tolerance to morphine in mice.
This study examined the role of kappa opioid receptors (KOR) in the mechanism underlying tolerance to the analgesic effects of morphine induced by chronic pain. The analgesic effect of morphine (10 mg kg(-1)), estimated by the tail-flick test in mice, gradually decreased during repeated daily morphine treatment. A significant decrease in the analgesic effect of morphine was seen on the fifth day of repeated morphine treatment compared with the first day. ⋯ Furthermore, an antisense oligodeoxynucleotide, but not a missense oligodeoxynucleotide, against KOR completely suppressed the inhibitory effect of formalin-induced pain on morphine tolerance. Naltrindole, an antagonist of delta opioid receptor, did not affect chronic-pain-induced tolerance to morphine. Our findings show that the inhibitory effect of chronic pain on analgesic tolerance to morphine is mediated by KOR rather than delta opioid receptors.
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J. Pharm. Pharmacol. · May 2007
Differential involvement of TRPV1 receptors at the central and peripheral nerves in CFA-induced mechanical and thermal hyperalgesia.
Transient receptor potential vanilloid 1 (TRPV1) antagonists are known to attenuate two typical symptoms of inflammatory hyperalgesia: thermal and mechanical. However, it is not clear whether the sites of participation of TRPV1 for each symptom are different. In this study, we clarified the difference between the site of TRPV1 involvement in both symptoms by analysing the anti-hyperalgesic activity of two kinds of TRPV1 antagonists given locally (i.e. intraplantarly and intrathecally) in rats with CFA (complete Freund's adjuvant)-induced inflammation. ⋯ Regression analysis showed that a correlation exists between the inhibitory effects on thermal hyperalgesia and mechanical hyperalgesia after intrathecal administration (correlation factor = 0.6521), but not after intraplantar administration (correlation factor = 0.0215). These data suggest that TRPV1 in the peripheral endings of the primary afferents plays a key role in thermal hyperalgesia, but it makes only a minor contribution in CFA-induced mechanical hyperalgesia. Furthermore, it is suggested that the spinal TRPV1 is critical in the development of both types of hyperalgesia.