European journal of pharmacology
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Most of renin-angiotensin system (RAS) gene polymorphisms have not yet been studied in the Iranian population. In the present study, the frequencies of common polymorphisms in the RAS genes, including angiotensin-converting enzyme (ACE) insertion/deletion (I/D) and three single-nucleotide polymorphisms (SNPs), i.e., A-240T, T-93C and A2350G, angiotensinogen M235T, angiotensin II receptor type 1 A1166C and angiotensin II receptor type 2 C3123A variants were determined in DNAs extracted from venous blood of 104 healthy Iranian volunteers. Genotyping was performed by PCR-RFLP method. ⋯ In conclusion, combined polymorphisms of A-240T and A2350G seem to affect serum ACE level as well as diastolic blood pressure in our study population. However, it also might be hypothesized that they are in strong linkage disequilibrium with other functional mutations not studied yet. Our findings revealed that gene interactions can play an important role in various biological conditions.
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Luteolin occurs in a variety of plants and possesses antioxidant and anti-inflammatory properties. However, its role in protection against ischemia-reperfusion injury in Sprague-Dawley rats has not been elucidated. In the present study, we tested the contractile function of left ventricular cardiomyocytes with different concentrations of luteolin: 0.5, 1.5, 2.5 and 5.0 μg/ml after simulated. ⋯ Luteolin inhibited the activation of Caspase3 after ischemia-reperfusion in cardiomyocytes. Furthermore, luteolin at 10.0 μg/ml improved ischemia-reperfusion induced myocardial function, by improving heart rate, +dp/dt(max) and -dp/dt(max), and also limiting the decline of left ventricular systolic pressure (LVSP) and elevation of left ventricular end-diastolic pressure (LVEDP) to some extent. Our results demonstrated that luteolin prevents ischemia-reperfusion injury by reducing necrosis and apoptosis in rat cardiomyocytes.
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Persistent pain associated with inflammatory arthritis is an aggravating factor that decreases patients' quality of life. Current therapies for joint pain have limited effectiveness and produce unwanted negative side effects. Although the involvement of substance P and its cognate tachykinin receptor, NK(1), in joint inflammation has been extensively documented through animal experiments, the development of oral tachykinin NK(1) receptor antagonists against arthritis-induced pain has been unsuccessful in humans to date. ⋯ Administration of the tachykinin NK(1) receptor antagonist WIN 51708 or GR 82334 into the affected ankle joint at day 3 following intra-articular CFA injection reduced the mechanical hyperalgesia 12 h after the tachykinin NK(1) receptor antagonist injection and their analgesic effects persisted for at least 2 days. Histological examinations revealed that intra-articular WIN 51708 reduced the CFA-induced destructive changes in the cartilage. These findings suggest that intra-articular injection of tachykinin NK(1) receptor antagonists is a promising strategy for relieving the hyperalgesia that occurs in inflammatory arthritis.
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In this study, the antinociceptive, anti-hypernociceptive and toxic effects of orally administered (R)-Se-phenyl thiazolidine-4-carboselenoate (Se-PTC, 1-50 mg/kg) were evaluated in mice. Se-PTC did not change plasma aspartate (AST) and alanine aminotransferase (ALT) activities or urea and creatinine levels. Furthermore, in an open field test, Se-PTC did not alter the number of crossings and rearing. ⋯ Se-PTC (25 mg/kg) significantly inhibited nociceptive behavior induced by intrathecal (i.t.) injection of glutamate, N-methyl-D-aspartate (NMDA) and (±)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD), but failed to affect nociception induced by kainate and α-amino-3-hydroxy-5-mehtyl-4-isoxazolepropionic acid (AMPA). Mechanical hypernociception induced by carrageenan and Complete Freund's Adjuvant was attenuated by Se-PTC administration. These results indicate that Se-PTC produces antinociception in several models of nociception.
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Methotrexate is employed in low doses for the treatment of rheumatoid arthritis. One of the major drawbacks with methotrexate is hepatotoxicity resulting in poor compliance of therapy. Curcumin is an extensively used spice possessing both anti-arthritic and hepatoprotective potential. ⋯ Hepatoprotective potential of curcumin was also confirmed from histological evaluation. Sub-therapeutic dose of methotrexate elicited substantial anti-arthritic action when used in combination with curcumin implying that the latter potentiated its action. Concomitant administration of curcumin with methotrexate was also found to minimize liver damage.