Why honey is effective as a medicine. 1. Its use in modern medicine

Honey has been used as a medicine for thousands of years and its curative properties are well documented. However, modern medicine turned its back on honey and it is only now, with the advent of multi-resistant bacteria, that the antibiotic properties of honey are being rediscovered

Role of oxygen-derived free radicals on gastric mucosal injury induced by ischemia-reperfusion

A free radical is an unstable and highly-reactive chemical species capable of independent existence that contained one or more unpaired electrons in its outer orbital. A number of oxygen-derived free radicals (ODFRs) have been identified. However, superoxide (O-2) and hydroxyl (OHFNx01) radicals are extensively studied. The univalent reduc-tion of oxygen to water produces a number of highly-reactive chemical intermediates such as O-2 and OHFNx01, which are commonly-known as oxygen-derived free radicals. ODFRS may be formed from several sources as follows: a) mitochondrial cytochrome oxidase, b) xanthine oxidase, c) neutrophils and d) transitional metals. There are several important defense mechanisms to limit or to prevent the damage caused by excessive ODFRs activity. These antioxidant defenses can be divided into a) enzymatic defense mechanisms such as : superoxide dismutase (SOD): catalase: selenium-containing glutathione peroxidase and b) non-enzymatic defense mechanisms including: alpha-tocopherol; ascorbic acid; glutathione and any sulfhydryl-containing compounds

Vasorelaxant effect of nitric oxide releasing steroidal and nonsteroidal anti-inflammatory drugs

1. The effect of several nitric oxide releasing-non-steroidal anti-inflammatory drugs (NO-NSAID) and nitroprednisolone on blood vessel relaxation in vitro and in vivo was studied. Nitroflurbiprofen (NOF; EC(50), 688.8±93.8 μM), nitroaspirin (NOA; EC(50), 57.9±6.5 μM), nitroparacetamol (NOPARA; EC(50), 71.5±14.6 μM) and nitroprednisolone (EC(50), 15.1±1.4 μM) caused concentration-related relaxation of noradrenaline (NA)-contracted rat aortic rings. All NO releasing compounds tested were approximately three orders of magnitude less potent than sodium nitroprusside (SNP, EC(50), 35.7±3.5 nM). 2. The vasorelaxant effect of NOF and NOPARA in the rat aorta was potentiated by zaprinast (5 μM) and reduced by ODQ (5 μM). Flurbiprofen and paracetamol (100 μM) caused minimal (<10%) relaxation of the rat aorta and did not affect the response to SNP. The effect of NOF was unchanged in the presence of L-NAME (100 μM; EC(30), 181.8±35.1 μM cf. EC(30), 125.1±17.0 μM, P>0.05) but increased by removal of the endothelium (EC(30), 164.3±26.3 μM cf. EC(50), 688.8±93.8 μM, P<0.05). 3. NOF (0.1–50 μM) produced a small but not concentration-related vasodilation of the NA-preconstricted (i.e. ‘high tone') perfused rat mesentery preparation (cf. SNP, EC(30), 4.4±0.7 μM). In contrast, NOF (1–100 μM) produced concentration-related vasodilation of the ‘high tone' perfused rat kidney with an EC(50) of 33.1±4.4 μM. 4. Neither NOF (74 mg kg(−1), i.p.) nor NOA (91.9 mg kg(−1), i.p.) nor equimolar doses of flurbiprofen (50 mg kg(−1), i.p.) or aspirin (50 mg kg(−1), i.p.) affected mean arterial blood pressure (MAP) or heart rate (HR) of pentobarbitone-anaesthetized rats over a 1 h period. 5. NO-NSAID relax blood vessels in vitro by an NO-dependent mechanism. The absolute vasorelaxant effect of NO releasing drug varies greatly with the choice of compound and between blood vessel preparations

A comparison of the effect of nitroparacetamol and paracetamol on liver injury

Paracetamol (5 mmol kg(−1), i.p.) caused liver damage in rats as indicated by increased plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT) and glutamate dehydrogenase (GDH) activities. No change in plasma bilirubin or creatinine was noted. An equimolar dose of nitroparacetamol (a nitric oxide (NO)-releasing derivative of paracetamol) did not alter plasma levels of any of the markers of liver/kidney damage. No difference in plasma or liver paracetamol was apparent in animals injected with paracetamol or nitroparacetamol. These results indicate that NO released from nitroparacetamol exhibits hepatoprotective activity in these animals and suggest that nitroparacetamol may therefore be considered as a safer alternative to paracetamol in the clinic

Nitroparacetamol exhibits anti-inflammatory and anti-nociceptive activity

Nitroparacetamol (NCX-701) is a newly synthesized nitric oxide-releasing derivative of paracetamol. Following i.p. administration, nitroparacetamol inhibits carrageenan-induced hindpaw oedema formation (ED(50), 169.4 μmol kg(−1)) and mechanical hyperalgesia (ED(50), 156 μmol kg(−1)) in the rat. In contrast, the parent compound, paracetamol, exhibits no significant anti-oedema activity in this model (ED(50)>1986 μmol kg(−1), i.p.) and is markedly less potent than nitroparacetamol as an inhibitor of carrageenan-mediated hyperalgesia (ED(50), 411.6 μmol kg(−1), i.p.). In a second model of nociception (inhibition of acetic acid induced abdominal constrictions in the mouse), nitroparacetamol administered orally (ED(50), 24.8 μmol kg(−1)), was again considerably more potent than paracetamol (ED(50), 506 μmol kg(−1), p.o.). Thus, compared with paracetamol, nitroparacetamol not only exhibits augmented antinociceptive activity in both rat and mouse but, intriguingly, is also anti-inflammatory over a similar dose range

A comparison of the anti-inflammatory and anti-nociceptive activity of nitroaspirin and aspirin

1. Nitroaspirin (2.5–50 mg kg(−1), i.p. or 2.5–100 mg kg(−1), p.o.) and aspirin (2.5–100 mg kg(−1), i.p. or p.o.) exhibit anti-inflammatory activity in the carrageenan-induced hindpaw oedema model in the rat. When administered i.p., nitroaspirin was a more effective anti-oedema agent than aspirin particularly in the ‘early' phase (i.e. up to 60 min) of the response. The ED(50) values for nitroaspirin and aspirin as inhibitors of the ‘late' phase response (measured at 180 min) were 64.3 μmol kg(−1) and >555 μmol kg(−1), respectively. When administered p.o., neither nitroaspirin nor aspirin exhibited significant anti-inflammatory activity in the ‘early' phase and were of similar potency in the ‘late' phase. Thus, at the highest dose used (100 mg kg(−1), 360 min) orally administered nitroaspirin (aspirin in parenthesis) inhibited oedema formation by 46.9±1.6% (47.2±3.8%, both n=6, P<0.05). 2. Nitroaspirin and aspirin (25–200 mg kg(−1), p.o.) caused dose-related inhibition of the hyperalgesia to mechanical stimulation following intraplantar injection of carrageenan in the rat. ED(50) values were 365 μmol kg(−1) and 784 μmol kg(−1), respectively. Neither drug influenced the threshold for mechanical stimulation in the contralateral (i.e. untreated) hindpaw. 3. Nitroaspirin and aspirin (2.5–100 mg kg(−1), p.o.) caused dose-related inhibition of acetic acid induced abdominal constrictions in the mouse (ED(50) values of 154.7 μmol kg(−1) and 242.8 μmol kg(−1), respectively). 4. Nitroaspirin and aspirin (>200 mg kg(−1), p.o.) reduced the ‘late' phase (but not the ‘early' phase) of the formalin-induced hindpaw licking assay in the mouse. Similarly, nitroaspirin and aspirin (>50 mg kg(−1), p.o.) prolonged tail withdrawal latency following application of a noxious heat stimulus in the mouse