Radioprotective properties of indralin combined with cystamine and mexamine

The radioprotective properties of indralin when it is used in combination with cystamine and mexamine are studied in inbred mice and rats. The mice and rats are irradiated with γ rays emitted by ⁶⁰Co at doses of 9.0 and 9.5 Gy, respectively. A combined parenteral administration of indralin and cystamine in mice at doses of 25 mg/kg each is revealed to potentiate the radioprotective properties of indralin up to a level close to the ED₅₀ effect, while the separate application of these drugs in doses of 25 mg/kg each has no or a very weak radioprotective effect. Indralin (50 mg/kg) and mexamine (12 mg/kg) injected intraperitoneally in rats are found to almost completely eliminate the animal mortality caused by gastrointestinal acute radiation syndrome; the mortality in the control radiation group reaches 60% on the seventh day after the animals have been exposed to radiation at a dose of 9.5 Gy. However, if bone-marrow acute radiation syndrome develops under the above condition of super-lethal dose, the radioprotectors have a low radioprotective effect. Under the this condition, the combined application of indralin and mexamine in the same doses has 50% of radioprotective effect reached by applying these radioprotectors separately in double doses.     

Radioprotective properties of indralin combined with cystamine and mexamine

The study of indralin radioprotective properties at its joint application with cystamine and mexamine was carried out in the experiments on inbred mice and rats. The mice and rats were exposed to whole-body y-irradiation at a dose of 9.0 and 9.5 Gy, correspondingly. A combined parenteral administration ofindralin and cystamine at a dose of 25 mg/kg showed ponentiaton of indralin radioprotective properties up to a level of the ED50 effect versus the absence of or a weak radioprotective effect in the case of their separate application. In the experiments on rats, indralin (50 mg/kg) and mexamine (12 mg/kg) injected intraperitoneally almost completely eliminated the animal mortality from the intestinal syndrome of acute radiation sickness amounting in the control radiation group to 60% on the 7th day after exposure to radiation at a dose of 9.5 Gy. However, at the above conditions, radioprotectors at these doses had a low-level radioprotective action at the onset of the bone marrow syndrome of acute radiation sickness. Combined application of indralin and mexamine at the same doses and at the same conditions led to a radiation protection 50% as high as in the case when radioprotectors were applied separately at a double dose.     

Radioprotective activity of Polyalthia longifolia standardized extract against X-ray radiation injury in mice

The radioprotective effect of Polyalthia longifolia was studied in mice. P. longifolia treatment showed improvement in mice survival compared to 100% mortality in the irradiated mice. Significant increases in hemoglobin concentration, and red blood cell, white blood cell and platelet counts were observed in the animals pretreated with leaf extract. Pre-irradiation administration of P. longifolia leaf extract also increased the CFU counts of the spleen colony and increased the relative spleen size. A dose-dependent decrease in lipid peroxidation levels was observed in the animals pretreated with P. longifolia. However, although the animals pretreated with P. longifolia exhibited a significant increase in superoxide dismutase and catalase activity, the values remained below normal in both liver and the intestine. Pre-irradiation administration of P. longifolia also resulted in the regeneration of the mucosal crypts and villi of the intestine. Moreover, pretreatment with P. longifolia leaf extract also showed restoration of the normal liver cell structure and a significant reduction in the elevated levels of ALT, AST and bilirubin. These results suggested the radioprotective ability of P. longifolia leaf extract, which is significant for future investigation for human applications in developing efficient, economically viable, non-toxic natural and clinically acceptable novel radioprotectors.     

Effect of indralin on genetic disruption induced by radiation in mice

The effect of indralin on frequency of mutations induced by radiation in germ cells, reciprocal translocations, and testicle weight of male mice. The level of protective effect against genetic damage varied depending on the radiation dose and spermatogenesis stage. The values of the defense coefficient ranged from 0.16 to 0.35.     

The influence of combined application of quercetin and indralin on post-irradiation repair of hematopoiesis in acute radiation injury

Experiments on mice-hybrids F1(CBA x C57B1/6) have detected a favorable effect of the associated application of quercetin (30-60 minutes before y-exposure of an animal) and a radioprotectant of urgent action indralin (in the case of its application after y-exposure) on a post-irradiation repair of the hematopoietic tissue in acute radiation sickness after y-exposure at a non-lethal dose of 6.7 Gy, which manifested itself in the accelerated formation of endogenous spleen colonies and spleen mass recovery, as well as in the lesser degree of leukopenia on the 12th and the 16th day after acute radiation injury. Quercetin per se did not have a radio-protective effect.     

Connexins in salivary glands

Connexins (Cxs) make up a family of gap junction structural proteins that form hexameric assemblies in the plasma membranes of adjacent cells that interact to form intercellular channels. It has been demonstrated that many kinds of CXs are differentially expressed in a variety of tissues; however, there have been only a few studies of CX expression in rat salivary glands. The co-localization of CX26 and 32 was examined in the parotid glands. Double immunofluorescence revealed that CX26 and 32 were present in the same gap junction. Double immuno-electron microscopy showed co-localization of both CX26 and 32 on the same gap junctional membranes between acinar cells. These results suggest that CX26 and 32 may participate in regulation of secretory function and permeability of acinar cells in the rat parotid glands.     

Radioprotective properties of oxolinic acid during long-term exposure to radiation

The antioxidant activity of oxolinic acid was studied in mongrel mice during the prolonged (6-8 hours) exposure to ionizing radiation. The drug administered before irradiation was shown to increase (by 7 to 33 per cent) the survival rate of mice. The effect was maximum after the subcutaneous injection. The results obtained on the effect of oxolinic acid on DNA synthesis by bone marrow karyocytes are submitted.     

Transition from polyteny to polyploidy in salivary glands of Cecidomyiidae

Summary Quantitiative cytochemical studies of Rana catesbeiana liver cell nuclei indicated that these populations consist entirely of diploid non-proliferating nuclei. While DNA values were stable, nuclear size varied over a considerable range. These size variations were directly related to total nuclear protein content, but protein SH and S-S content appeared to be related to ploidy rather than volume. Protein bound tyrosine represents an intermediate case. The latter two fractions appear to be partially bound to nucleic acids, since removal of either class of nucleic acid leads to an increase in absorption values.This investigation was supported by a grant from the U.S. Public Health Service, GM-10003-03.Post-Doctoral Trainee under U.S. Public Health Training Grant to the Department of Pathology, University of Florida, 5 Tl GM 1142-03.Supported by a Career Development award from the National Institute of Child Health and Human Development, K 3-HD-6176-03.     

Comparative effectiveness of antioxidant melatonin and radioprotectors indralin and phenylephrine in local radiation injuries

In experiments on mice radioprotective properties of indraline, phenyleprine and melatonin were compared at topical application as an ointment at a place of local exposure of animal hind to a dose of 38.3 Gy of 60Co gamma-quanta. Factor of dose reduction was 1.27-1.32 for indraline (1-10% ointment) and 1.29 for phenyleprine (0.25% ointment). Antioxidants were low efficient at radiation skin burn. At later local radiation injuries, such as hind contracture, the efficiency of indraline was 1.33-1.5, that of phenyleprine was 1.28, and that of melatonine (2 and 5% ointment) was 1.23-1.47.     

Channels and transporters in salivary glands

According to the two-stage hypothesis, primary saliva, a NaCl-rich plasma-like isotonic fluid is secreted by salivary acinar cells and its ionic composition becomes modified in the duct sytem. The ducts secrete K⁺ and HCO₃^- and reabsorb Na⁺ and Cl^- without any water movement, thus establishing a hypotonic final saliva. Salivary secretion depends on the coordinated action of several channels and transporters localized in the apical and basolateral membrane of acinar and duct cells. Early functional studies in perfused glands, followed by the molecular cloning of several transport proteins and the subsequent analysis of mutant mice, have greatly contributed to our understanding of salivary fluid and the electrolyte secretion process. With a few exceptions, most of the key channels and transporters involved in salivary secretion have now been identified and characterized. However, the picture that has emerged from all these studies is one of a complex molecular network characterized by redundancy for several transport proteins, compensatory mechanisms, and adaptive changes in health and disease. Current research is directed to the molecular interactions between the determinants and the ways in which they are regulated by extracellular signals and intracellular mediators. This review focuses on the functionally and molecularly best-characterized channels and transporters that are considered to be involved in transepithelial fluid and electrolyte transport in salivary glands.     

Aquaporins in salivary glands and pancreas

Background

Salivary glands and pancreas are involved in saliva secretion, pancreatic fluid secretion and insulin secretion. These functions are essential for proper oral, pancreatic and glucose homeostasis. Aquaporins are water-permeable transmembrane protein involved in the physiology of these secretory gland functions.

Scope of review

This review gives an overview of the morphology of salivary glands and pancreas, the expression and localization of aquaporins, the secretion roles and mechanisms, the physiological roles of aquaporins, and the role of aquaporins in pathophysiological conditions.

Major conclusions

Several aquaporins are expressed in salivary glands and pancreas, and some play important physiological roles. Modulation of aquaporin expression and/or trafficking may contribute to the pathogenesis of diseases affecting salivary glands and pancreas glands such as xerostomic conditions, pancreatic insufficiencies and diabetes.

General significance

Aquaporins are involved in physiological and pathophysiological processes in salivary glands and pancreas. They could represent therapeutic targets for the treatment of diseases affecting the salivary glands and pancreas. This article is part of a Special Issue entitled Aquaporins.     

ADP-Ribosyl cyclase in rat salivary glands

Both the Ca(2+)-releasing mechanism induced by cyclic ADP-ribose (cADPR) and the ADP-ribosyl cyclase (ADPRC) activity that converts NAD(+) to cADPR were observed in a variety of cell types. We studied the ADPRC activity in rat major salivary glands that include parotid gland (PG), submandiblar gland (SMG), and sublingual gland (SLG). The enzyme activity responsible for cADPR synthesis was detected by spectrofluorometric assay using NGD(+) as a substrate. The enzyme activities in SLG, SMG, and PG were about 400, 30, and 40 nmol/min/g tissue, respectively, in 5-week-old rats. The highest value was observed in SLG and this value was higher than those in other tissues; e.g., spleen (200 nmol/min/g tissue). The enzyme activity in SLG increased gradually after birth and showed a maximum value at 3 weeks. On the other hand, the enzyme activities almost did not change in both PG and SMG between 0 and 9 weeks. In spite of the high ADPRC activity in SLG, we could not detect the cADPR-induced Ca(2+)-release from SLG microsomes. These results suggest that the ADPRC in SLG does not function through Ca(2+)-release observed in various tissues.     

Radioprotective properties of eckol against ionizing radiation in mice

We have investigated the radioprotective efficacy of eckol, a component of brown seaweed Ecklonia cava, against the gamma ray-induced damage in vivo. Our results showed that eckol significantly decreased the mortality of lethally irradiated mice. The mechanisms of eckol's protection were found to include: an improvement in hematopoietic recovery, the repair of damaged DNA in immune cells and an enhancement of their proliferation, which had been severely suppressed by ionizing radiation. Thus, we propose eckol as a candidate for adjuvant therapy to alleviate radiation-induced injuries to cancer patients.