Ozone ameliorates age-related oxidative stress changes in rat liver and kidney: effects of pre- and post-ageing administration.

The ageing process is known to be accompanied by increased oxidative stress and compromised antioxidant defenses. Controlled ozone administration has been shown to be effective in various pathophysiological conditions with an underlying oxidative burden. However, its effect on the biochemical alterations associated with the ageing process has been rarely studied. Therefore, the present work was carried out to study the role of ozone in counteracting the state of oxidative stress associated with ageing in rat liver and kidneys using two experimental models. In the pre-ageing model, ozone was administered prior to the onset of ageing at adulthood and continued after the start of the ageing process (3-month-old rats until the age of 15 months). While in the post-ageing model, ozone was administered after ageing has begun and lasted for one month (14-month-old rats until the age of 15 months). The pre-ageing ozone administration effectively reduced lipid and protein oxidation markers, namely, malondialdehyde and protein carbonyl levels and decreased lipofuscin pigment deposition in rat liver and kidneys. Moreover, it significantly restored hepatic and renal reduced glutathione (GSH) contents and normalized cytosolic hepatic glutathione peroxidase activity. Similar but less pronounced effects were observed in the post-ageing ozone-treated group. Nevertheless, in the latter model ozone administration failed to significantly affect liver and kidney lipofuscin levels, as well as kidney GSH contents. These data provide evidences for potentially positive effects of pre-ageing ozone therapy in neutralizing chronic oxidative stress associated with ageing in rat liver and kidneys.

Effect of calcium channel antagonists in modifying the inhibitory influence of adenosine on insulin secretion.

The present work was performed to study the effect of two calcium channel antagonists, namely verapamil (CAS 52-53-9) and nifedipine (CAS 21829-25-4) in modifying the inhibitory influence of adenosine on insulin secretion from isolated rat pancreatic islets. The combined effect of adenosine and these agents on serum insulin and glucose levels in vivo was also investigated. Both verapamil and nifedipine at 100 mumol/l and 1 mumol/l, respectively, produced a significant inhibition of glucose-stimulated insulin secretion from pancreatic islets. Combination of these agents with adenosine 10 mumol/l did not modify the inhibitory effect of adenosine on insulin secretion. Verapamil (21.6 mg/kg b.wt.) and nifedipine (5.4 mg/kg b.wt.) intraperitoneally injected prior to glucose loading produced a significant increase in serum glucose with an accompanied decrease in serum insulin levels. Concurrent administration of verapamil with adenosine neither affected the hyperglycaemic nor the hypoinsulinaemic effects of adenosine, whereas combined administration of nifedipine and adenosine decreased the hyperglycaemic effect of adenosine but not its hypoinsulinaemic effect. These results may indicate that these calcium channel antagonists do not interact with adenosine receptors which mediate its inhibitory effect on insulin secretion.

Combined effect of adenosine, alpha adrenergic and adenosine antagonists on serum insulin and insulin secretion from rat pancreatic islets.

1. The effect of adenosine separately or in combination with alpha-1 adrenergic antagonist prazosin and alpha-2 adrenergic antagonist yohimbine as well as adenosine antagonists 8-phenyltheophylline and xanthine amine conjugate on glucose-induced insulin secretion from isolated rat pancreatic islets was studied. 2. Their in vivo effects on serum glucose and insulin levels were also investigated. Adenosine at 10 and 100 microM inhibited significantly, insulin secretion from the isolated islets whereas at 10 mM slightly increased the secretion of insulin. 3. Prazosin used at 100 microM inhibited insulin secretion. When it combined with adenosine (10 microM) it augmented the inhibitory effect of adenosine. 4. In vivo prazosin (21 mg/kg body wt) caused a hyperglycaemia which was accompanied by hypoinsulinaemia. 5. Concurrent administration of this drug with adenosine neither affect the hyperglycaemic nor the hypoinsulinaemic effects of adenosine. 6. On the other hand, yohimbine (100 microM) has no effect neither separately nor in combination with adenosine (10 microM) in modulating the inhibitory effect of adenosine on insulin secretion. 7. When Yohimbine administered at 19.5 mg/kg body wt it did not alter serum glucose but it markedly increased the serum insulin level. Its combined administration with adenosine reduced the hyperglycaemic effect of adenosine with a remarkable increase in serum insulin. 8. Both adenosine-antagonists were ineffective in alteration of insulin secretion. 9. However, combination of 8-phenyltheophylline with adenosine (10 microM) totally blocked the inhibitory effect of adenosine on insulin secretion while xanthine amine conjugate failed to prevent this effect of adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)