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Objective: In the present work, we evaluated the effect of exposing the submandibular glands (SMG) to radiation, studying different functional parameters such as salivary secretion, nitric oxide (NO) production, reactive oxygen species formation, prostaglandin (PGE) content and apoptosis., Methods: We irradiated rats in the head and neck region with a single dose of gamma-ray radiation of 15 Gy. Two hours after radiation, we measured norepinephrine-induced salivary secretion. After that, the SMG were dissected, and in this tissue, we measured the activity of NO synthase (NOS), the PGE content, the amount of reactive oxygen species, apoptotic cells and mitochondrial inducible NOS (iNOS) expression., Results: We found that radiation decreased salivary secretion when 10 and 30 microg/kg of norepinephrine was administered via the right femoral vein. We observed that iNOS activity was reduced and PGE content increased after radiation in SMG, indicating that NO and PGEs may participate in salivary secretion. The expression of mitochondrial NOS was increased after radiation leading to the formation of large amounts of NO that acts as a proapoptotic signal. In fact, we observed an augmentation in apoptotic cells. In this study, we also observed an increase in lipid peroxidation induced by radiation that may contribute to tissue damage., Conclusions: Our results indicate that radiation induced a decrease in salivary secretion and SMG iNOS activity, meanwhile the PGE content, the lipid peroxidation and apoptosis increased in the tissue. These modifications decrease salivary secretion.

Results of preclinical studies suggesting that the efficacy of molecular therapies is enhanced when they are combined with radiation have generated a surge of clinical trials combining these modalities. We reviewed the literature to identify the rationale and experimental foundation supporting the use of cyclooxygenase-2 (COX-2) inhibitors with standard radiotherapy regimens in current clinical trials. Radiation affects the ability of cells to divide and proliferate and induces the expression of genes involved in signaling pathways that promote cell survival or trigger cell death. Future advances in radiotherapy will hinge on understanding mechanisms by which radiation-induced transcription of genes governs cell death and survival, the selective control of this process, and the optimal approaches to combining this knowledge with existing therapeutic modalities. COX-2 is expressed in all stages of cancer, and in several cancers its overexpression is associated with poor prognosis. Evidence from clinical and preclinical studies indicates that COX-2-derived prostaglandins participate in carcinogenesis, inflammation, immune response suppression, apoptosis inhibition, angiogenesis, and tumor cell invasion and metastasis. Clinical trial results have demonstrated that selective inhibition of COX-2 can alter the development and the progression of cancer. In animal models, selective inhibition of COX-2 activity is associated with the enhanced radiation sensitivity of tumors without appreciably increasing the effects of radiation on normal tissue, and preclinical evidence suggests that the principal mechanism of radiation potentiation through selective COX-2 inhibition is the direct increase in cellular radiation sensitivity and the direct inhibition of tumor neovascularization. Results of current early-phase studies of non-small-cell lung, esophageal, cervical, and brain cancers will determine whether therapies that combine COX-2 inhibitors and radiation will enter randomized clinical trials.

The experiments with dogs exposed to 100 Gy of accelerated electrons demonstrated a significant role of prostaglandins in the origin of early post-radiation dyspepsia. Their significance for genesis of post-radiation dyspeptic disturbance caused by exposure to superhigh doses becomes clear-cut when a combination of an antiemetic and inhibitors of prostaglandin biosynthesis is used. A study of the effect of dexamethasone, a blocker of arachidonic acid release, and of voltaren, an inhibitor of prostaglandin formation from cyclic endoperoxide, suggests that it would be appropriate to prevent radiation vomiting and diarrhea by inhibiting both of the above stages in prostaglandin biosynthesis.

Prostaglandin G/H synthase (PGHS) has been shown to generate peroxides to a significant extent in the retina and absorbs light at the lower end of the visible spectrum. We postulated that PGHS could be an important initial source of peroxidation in the retina exposed to light, which would in turn alter retinal function. Exposure of pig eyes (in vivo) to light (350 fc/3770 lx) caused after 3 h a 50% increase and by 5 h a 30% decrease in a- and b-wave amplitudes of the electroretinogram (ERG) which were comparable at 380-650 nm and 380-440 nm but were not observed at wavelengths > 450 nm. These effects of light were prevented by free radical scavengers (dimethylthiourea and high-dose allopurinol) and PGHS inhibitors (naproxen and diclofenac), but stable analogs of prostaglandins did not affect the ERG. Both increases and subsequent decreases in ERG wave amplitudes following light exposure in vivo were associated with increases in retinal prostaglandin and malondialdehyde (peroxidation product) levels, which were inhibited by the nonselective PGHS blockers, naproxen and diclofenac. Similar observations were made in vitro on isolated porcine eyecups as well as on retinal membranes exposed to light (250 fc/ 2700 lx) 380-650 nm and 380-440 nm but not at > 500 nm. Both PGHS-1 and PGHS-2 contributed equivalently to light-induced prostaglandin synthesis, as shown after selective PGHS-2 blockers, but mRNA expression of PGHS-1 and 2 was not affected by light. Finally, light stimulated activities of pure PGHS-1 and PGHS-2 isozymes, and these were also shown to produce superoxide radical (detected with fluorogenic spin trap, proxyl fluorescamine). Taken together, data suggest that PGHS- (1 and 2) is activated by short wavelength visible light, and in the retina is an important source of reactive oxygen species which in turn alter retinal electrophysiological function. PGHS thus seems a likely chromophore in setting forth photic-induced retinal injury. Findings provide an explanation for increased sensitivity of the retina to visible light predominantly at the far blue range of its spectrum.

In experiments with dogs and rats it has been shown that early after high doses of irradiation, the content of prostaglandins in the blood plasma increases, whereas in the intestinal tissues it decreases. The inhibitors of prostaglandins synthesis indomethacin and voltaren hinder the development of early digestive disturbances, normalize the intestine absorptive and propulsive functions and make post-irradiation hypokinesia less pronounced. Possible mechanisms of the prostaglandins involvement in the genesis of prodromal radiation syndrome are discussed.

The paper shows the high therapeutical efficiency of combined He-Ne laser therapy in patients with coronary heart disease. Its effect on the thromboxane-prostacyclin system is one of the mechanisms of laser impact. The combined He-Ne laser therapy promotes normalization of the level of thromboxane B2 and its ratio to the metabolite prostacyclin.

Ultraviolet (UV) light exposure substantially modifies the host immune response, in part through the synthesis of prostaglandins. Work examining the mechanisms by which UV irradiation stimulates prostaglandin synthesis has focused on mediators that increase in quantity after irradiation. The present work demonstrates that UV irradiation injury increases the sensitivity and maximum response of keratinocytes to bradykinin, suggesting that agonist quantities need not increase in injured tissue to contribute to inflammation. The ability of UV injury to increase bradykinin-stimulated prostaglandin synthesis is not limited to keratinocytes, as irradiation produced a similar response in fibroblasts. Receptor binding studies demonstrate that the enhanced response of irradiated cells is not due to increased bradykinin binding. These data suggest that UV irradiation may cause cells to increase their response to an array of inflammatory mediators present in injured tissue, whether or not the quantity of the mediator increases.

Irradiation can have a profound effect on intestinal motor activity. Previous studies have suggested that prostaglandins may play some role in radiation-induced enteritis. The present study investigated the effects of abdominal X-irradiation with or without indomethacin treatment on jejunal myoelectric activity and prostaglandin synthesis by measuring the prostaglandin content of mesenteric arterial and venous plasma and in the intestinal lumen in dogs. After X-irradiation, venous concentrations and arteriovenous concentration differences of prostaglandin (PG)E2, PGF2 alpha, and 6-keto-PGF1 alpha increased markedly. The increased venous concentrations were in part attributable to increased mucosal and/or submucosal synthesis by inference from increased concentrations of these metabolites assayed from the jejunal lumen. Irradiation produced histological damage to the mucosa and submucosa and abnormalities in the migrating motor complex, jejunal slow waves, and a decrease in spike burst activity. Inhibition of prostaglandin synthesis by treating the animals with indomethacin reduced the severity of illness, the histological injury, and changes in myoelectric activity induced by irradiation. Such treatment should be evaluated further to treat patients exposed to large doses of irradiation.

In experiments with dogs and monkeys a study was made of the dynamics of the content of prostaglandins (PG) and cyclic nucleotides after gamma irradiation. In dogs irradiation with lethal doses (3.1 and 50 Gy) caused a short-term, evidently stress growth of cAMP, PGE and PGF2 alpha levels. At the height of radiation sickness PGF2 alpha and cGMP content decreased considerably. Irradiation of monkeys with a nonlethal dose of 3.2 Gy changed PGE and PGF2 alpha levels to a lesser extent, while concentrations of cyclic nucleotides varied but their ratio remained stable.

Some biochemical disorders in the animals' central nervous system mainly in brain have been analysed after the exposure to superlethal doses of ionizing radiation as well in a state of the so-called early transient incapacity. The metabolism of gamma-aminobutyric acid, ammonia, histamine, cyclic nucleotides, prostaglandins and other biologically active substances is compared. Their investigation as metabolic regulators and modulators for nerve tissue seems to be of particular importance for deciphering the molecular mechanisms of changes in the central nervous system functional state and for discovering the possibility of its maintaining at a given level of activity.

One to 7 days after whole body exposure of mice to a single dose of 700 R of x-rays, little or no change was detected in prostaglandin-like activity in the brain, blood and seminal vesicles. Slight increases in intestinal and renal tissue were not significant. In the lung, mean activity rose from 62 ng/g to a transient peak of 145 ng/g wet weight on the fourth day (P less than 0.05). In the spleen, mean levels rose steadily from 13.2 ng/g to 259 ng/g on the fourth day (P less than 0.01), and were still 184.4 ng/g on the seventh day. 2 Prostaglandin-like activity was measured 4 days after single doses of 200-700 R. In the lung, a significant rise was produced by 600 and 700 R, and in the spleen by 200-700 R. 3 Thin layer chromatography showed that part of the prostaglandin-like activity in spleen extracts had RF similar to that of [3H]-prostaglandin E1, and part to that of [3H]-prostaglandin F2alpha. 4 Splenic tissue from mice exposed to 700 R four days earlier, inactivated prostaglandin E1 less potently than did tissue from non-irradiated mice.

The influence of gamma-rays 60Co and fast neutrons on intravascular platelet aggregation and prostacyclin activity of the vascular wall has been studied. It has been shown that 1-6 hours after irradiation of CBA mice, a great number of bone marrow platelets clump to form fibrin fibrils that often close completely the vascular lumen. Experiments with irradiated rats and guinea-pigs have demonstrated the reduction of prostacyclin-like activity in the abdominal aorta wall.

The authors present the idea of the importance of studying the mechanism of biochemical reception of biologically active compounds (BAC) particularly the reception of prostaglandins after the effect of ionizing radiation on eucaryotes as a factor playing a significant role in understanding the radiation sickness pathogenesis. The perspectives of studying BAC reception are prognosticated for searching new radiomodifying agents (radioprotectors and means for treating radiation sickness).

The trend in immunobiological responses to transcerebral action of decimeter microwaves was studied in intact rabbits. Transcerebral microwaves (120 mW/cm2) can alter functional activity of certain links of endocrine system due to possible activation of hypothalamus and hypophysis exposed to microwave electromagnetic field. Such exposure given in courses at early stages leads to an increase in the number of antibody-forming cells in the spleen, whereas total number of splenocytes is on the decrease.