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PubMed1994

Effects induced by cysteamine on chemically-induced nociception in mice.

The effects were investigated of cysteamine--a well known somatostatin depletor--on the pain induced by chemical stimuli in mice. Cysteamine injected intraperitoneally 4 h before the test at doses of 50 and 100 mg/kg reduced the second phase of the licking response which was induced by formalin injected into the hind paw. Furthermore, cysteamine administered at the doses of 10, 50 and 100 mg/kg reduced the writhing induced by acetic acid. Naloxone, yohimbine and CGP 35348 administered in cysteamine-pretreated animals were not able to change the cysteamine antinociceptive effects in the formalin test. Intrathecally injected somatostatin was able to revert the cysteamine antinociceptive effects in the second phase of the formalin test and in the writhing test, whereas intracerebroventricularly injected somatostatin reduced the antinociceptive effects induced by cysteamine in the second phase of the formalin test. Intrathecally injected cyclo(7-aminoheptanoyl-Phe-D-Trp-Lys-Thr[Bzl])--a reported somatostatin antagonist--increased cysteamine antinociceptive effects in the second phase of the formalin test and in the writhing test. These results suggest that somatostatin is involved in the effects of cysteamine on the nociceptive threshold.

Amino Acid Sequence↗
PubMedDate not supplied

Immunohistochemical analysis of the effects of cysteamine on somatostatin-like immunoreactivity in the rat central nervous system.

The brain and spinal cord of untreated and cysteamine-treated rats were analyzed with immunohistochemistry using antisera raised against somatostatin (SOM)-28(1-14) and SOM-28(15-28). Sections incubated with increasing dilutions of antiserum were evaluated subjectively on coded slides and with computer-assisted image analysis. For control experiments, antisera raised against methionine-enkephalin, neuropeptide Y (NPY) and dynorphin (DYN)(1-13) were used. The latter antiserum does not visualize the conventional DYN systems in the brain, but reacts with an unknown epitope, which here could be shown to be present in SOM neurons. In cysteamine-treated rats a marked decrease in SOM-28(15-28)-like immunoreactivity (1.1) could be recorded subjectively at all antibody concentrations in fibers in several brain areas, including nucleus accumbens, tuberculum olfactorium and the hypothalamic ventromedial and arcuate nuclei. In these areas SOM-LI is fairly weak in untreated rats. In SOM-rich regions such as the median eminence and the dorsal horn of the spinal cord, the depleting effect of cysteamine could be recorded subjectively only when diluted antisera were used. Image analysis confirmed the subjective analysis, and, in addition, differences between controls and cysteamine-treated rats could be shown also at high antiserum concentrations. SOM-28(15-28)-immunoreactive cell bodies could be seen in the brains of either control or drug-treated rats. No effect of cysteamine could be observed when antiserum raised to SOM-28(1-14) was used. Cysteamine did not seem to affect enkephalin-LI, NPY-LI or an epitope in SOM neurons reacting with DYN(1-13) antiserum. After preabsorption of SOM-28(15-28) antiserum with SOM-28(15-28) peptide, the staining patterns described above disappeared completely. However, if the SOM-28(15-28) peptide was pretreated with a high concentration (1 M) of cysteamine before being used for absorption with SOM antiserum, no blocking effect could be observed. The present results demonstrate with immunohistochemistry that cysteamine causes depletion of SOM-28(15-28) in fibers but apparently not in cell bodies. No effects on SOM-28(1-14)-LI were observed. This supports earlier evidence that cysteamine interacts with the disulphide bond in the SOM-28(15-28) molecule. The present results also emphasize that when analyzing drug effects on peptide neurons with immunohistochemical techniques, it is important to use dilution series of antibodies and preferably to carry out the analysis with objective image analysis methods.

Animals↗
PubMed1985

Cysteamine and propionitrile inhibit the rise of duodenal mucosal alkaline secretion in response to luminal acid in rats.

Effects of subulcerogenic doses of cysteamine (100 mg/kg s.c.) and propionitrile (5 mg/kg) on alkaline secretion by duodenal surface epithelium and pH at the surface of this mucosa were assessed in duodenum of anesthetized rats. Alkaline secretion was titrated in situ, using segments of duodenum just distal to the Brunner's glands area and devoid of pancreatic HCO3-. Surface pH was measured by advancing pH-sensitive microelectrodes from the luminal solution to the epithelial cell surface. Proximal duodenum from bullfrogs was used to study effects of cysteamine on alkaline secretion in vitro. Cysteamine caused an increase in alkaline secretion in the rat during the first hour after administration, but rates after 5 and 20 h were the same as in controls and cysteamine (1 mg/ml) had no effect on secretion in vitro. Neither in vitro nor in vivo did cysteamine affect the rise in alkaline secretion in response to exogenous prostaglandin E2 (and dibutyryl-cyclic adenosine monophosphate). Luminal acid is a potent stimulant of duodenal mucosal alkaline secretion. By delayed (5 h) actions, both cysteamine and propionitrile inhibited the rise in alkaline secretion in response to a 5-min exposure to luminal acid with pH 2.00 in the rat. Cysteamine also depressed the ability of this mucosa to maintain a high rate of alkaline secretion during sustained exposure at pH 2.00 but had no such effect at pH 5.00. The former resulted in acidification of the pH gradient at the mucosal surface. Cysteamine is thus probably without effect on the HCO3- secretory process itself but impairs the ability of the duodenal mucosa to respond to acid. Inhibition of mechanisms mediating this response may contribute to the duodenal ulcerogenic actions of cysteamine and propionitrile.

2,4-Dinitrophenol↗
PubMed2003

Supplementation with cysteamine during maturation and embryo culture on embryo development of prepubertal goat oocytes selected by the brilliant cresyl blue test.

Our previous studies have shown that the addition of 100 mircroM cysteamine to the in vitro maturation (IVM) medium increased the embryo development of prepubertal goat oocytes. The aim of the present study was to evaluate the effect of adding different concentrations of cysteamine to the IVM medium and to the in vitro embryo culture medium (IVC) on the embryo development of prepubertal goat oocytes selected by the brilliant cresyl blue (BCB) test. Oocytes were exposed to BCB and classified as: oocytes with a blue cytoplasm or grown oocytes (BCB+) or oocytes without blue cytoplasm or growing oocytes (BCB-). In Experiment 1, oocytes were matured in a conventional IVM medium supplemented with 100 microM, 200 microM or 400 microM cysteamine. In Experiment 2, oocytes were matured with 400 microM cysteamine and following in vitro fertilization (IVF) were cultured in SOF medium supplemented with 50 microM and 100 microM cysteamine. In Experiment 1, BCB+ oocytes matured with 100 microM and 200 microM cysteamine showed higher normal fertilization and embryo development rates than BCB- oocytes. Oocytes matured with 400 microM cysteamine did not present these differences between BCB+ and BCB- oocytes. In Experiment 2, the addition of 50 microM and 100 microM cysteamine to culture medium did not affect the proportion of total embryos obtained from BCB+ oocytes (35.89% and 38.29%, respectively) but was significantly different in BCB- oocytes (34.23% and 29.04%, respectively, P < 0.05). In conclusion, the addition of 400 microM cysteamine to the IVM improved normal fertilization and embryo development of BCB- oocytes at the same rates as those obtained from BCB+ oocytes. The proportions of morulae plus blastocyst development were not affected by the treatments.

Animals↗
PubMed1983

Mucosal enzyme activities, with special reference to enzymes implicated in bicarbonate secretion, in the duodenum of rats with cysteamine-induced ulcers.

1. Duodenal mucosa was collected from control rats and from animals which had received cysteamine, cysteamine plus cimetidine or pentagastrin. Animals which received cysteamine with or without cimetidine developed acute duodenal ulcers. Cysteamine treatment resulted in gastric acid hypersecretion, which was largely abolished by concurrent cimetidine administration. 2. Activities of enzymes implicated in bicarbonate secretion, HCO3--activated ATPase, carbonic anhydrase and Na+ + K+-activated ATPase, were measured in the duodenal mucosa of control rats and animals 24 h after subcutaneous administration of cysteamine. Assays of these enzymes in duodenal mucosal homogenates from animals with cysteamine-induced ulcers showed significant decreases in HCO3--activated ATPase and carbonic anhydrase activities compared with controls. 3. Alkaline phosphatase activity also fell significantly in the cysteamine-treated animals, and possibly reflects the HCO3---activated ATPase activity in the brush-border membrane. In contrast, activities of other marker enzymes from the brush-border membrane and from several intracellular organelles were unchanged, indicating an absence of gross organelle pathology in this experimental model. 4. Similar changes in enzyme activity were not caused by treatment with pentagastrin. Administration of cimetidine with the cysteamine did not protect the animals against ulceration, and the activity of HCO3--activated ATPase was persistently decreased. However, the carbonic anhydrase activity was unaltered in this latter group, compared with controls. 5. These findings suggest that in cysteamine-induced duodenal ulceration both gastric acid hypersecretion and impaired duodenal resistance occurs. It is suggested that decreased activities of key enzymes implicated in HCO3--secretion may reflect the biochemical basis for the decreased mucosal resistance.

Animals↗
PubMed1999

Male pronuclear formation in denuded porcine oocytes after in vitro maturation in the presence of cysteamine.

The present study was conducted to examine effects of cysteamine in culture medium on progression of meiosis, glutathione (GSH) content, kinase activities (histone H1 kinase and mitogen-activated protein kinase), and male pronuclear formation after in vitro insemination of cumulus-denuded oocytes (DOs) in the pig. DOs, obtained by mechanically removing cells from cumulus-oocyte complexes (COCs) with a small-bore pipette, were cultured for 45 h in TCM199 supplemented with sodium pyruvate, gonadotropins, estradiol, and 10% porcine follicular fluid, with or without cysteamine (150 microM). Maturation rates of DOs cultured with and without cysteamine were not different (60-70%) but were significantly lower than those of COCs (90-100%) (p < 0.05). GSH content of matured DOs cultured with cysteamine was significantly higher than that of DOs cultured without cysteamine (p < 0.05). Values for both types of kinase activity in matured DOs cultured with and without cysteamine were not different (p > 0.05). After in vitro insemination, DOs cultured with cysteamine showed significantly higher rates of male pronuclear formation (80.3 +/- 3.0%) than DOs cultured without cysteamine (16.4 +/- 0.5%) (p < 0.05). These results indicate that the addition of cysteamine to culture medium increased oocyte GSH content and promoted male pronuclear formation after sperm penetration of porcine DOs but had no effects on their maturation rates or kinase activities.

Animals↗
PubMed1997

Evidence for a significant role of gastrin in cysteamine-induced hypersecretion of gastric acid.

Cysteamine has been known to stimulate gastric acid secretion and to induce duodenal ulcers in rats. We investigated the role of gastrin in cysteamine-induced acid hypersecretion in the perfused rat stomach. Intravenous infusion of cysteamine (75 mg/kg/h) resulted in a significant increase in acid secretion, which was accompanied by a marked increase in the plasma gastrin concentration. The cysteamine-induced increase in gastric acid secretion was completely blocked by i.v. injection of anti-gastrin rabbit serum (500 microliters). In addition, i.v. infusion of a CCK-B/gastrin receptor antagonist (L-365,260) (1 mg/kg/h) also suppressed the cysteamine-induced increase in acid secretion. Atropine significantly, but only partially, inhibited the increase. The elevated plasma gastrin levels induced by cysteamine were unaffected by atropine and L-365,260. In conclusion, cysteamine-induced acid hypersecretion is mediated mainly by cysteamine-induced gastrin release and partially by cholinergic factors. Furthermore, gastrin release caused by cysteamine appears to be independent of cholinergic tone.

Animals↗
PubMed1992

Cysteamine protects gastric epithelial cell monolayers against drug induced damage: evidence for direct cellular protection by sulphydryl compounds.

The sulphydryl containing drug cysteamine protects gastric mucosa in vivo against acute injury. It is not known whether this protection includes a direct effect on gastric cells. Using gastric epithelial cell monolayers derived from a well differentiated human cell line, we evaluated whether cysteamine protects against taurocholate or indomethacin induced damage in conditions which completely exclude the influence of vascular, hormonal, and neural factors. The effect of cysteamine on prostaglandin production by monolayer cells in vitro was also assessed. Cysteamine decreased damage brought about by sodium taurocholate and indomethacin by 40% (p less than 0.01) and 50% (p less than 0.01) respectively. The sulphydryl blocker iodoacetamide prevented the protective effect of cysteamine. Pretreatment with indomethacin, which inhibited prostaglandin E2 output by 60%, did not prevent protection by cysteamine; incubation with cysteamine decreased prostaglandin E2 production by cultured cells. We conclude that (i) cysteamine directly protected gastric epithelial cells in vitro (ii) this protection occurred with indomethacin, which interferes with cellular metabolism of prostaglandins, and taurocholate, whose damaging action at neutral pH is unrelated to interference with prostanoid metabolism, (iii) cysteamine protection in vitro is unrelated to endogenous prostaglandins and is probably mediated by endogenous sulphydryl compounds.

Cell Line↗
PubMed1983

[Effects of cysteamine on canine splanchnic D-cells].

It has recently been reported that the oral administration of cysteamine causes a depletion of somatostatin content in various tissues of the rat concomitant with duodenal ulcer. Producing somatostatin deficient animals is important for understanding the role of somatostatin in the homeostasis of ingested nutrients. The present experiment was designed to investigate the acute and chronic effects of cysteamine on canine splanchnic D-cells. When 2 g of cysteamine was administered to normal mongrel dogs, it caused a bloody stool. However, somatostatin-like immunoreactivity (SLI) levels in the peripheral vein did not change although the insulin, glucagon and glucose levels increased. In isolated perfused canine pancreases, cysteamine (10 microM-10 mM) showed no specific effect on the somatostatin secretion. The chronic effect of systeamine on the canine D-cells was studied by using dogs to which cysteamine was administered 3 times (2 g, P.O., every 10 days) at least 4 weeks before the experiment (cysteamine dogs). Hormone secretions from the perfused pancreases isolated from the cysteamine dogs were normal. The increases in somatostatin-14 levels in the pancreaticoduodenal vein, short gastric vein and gastroepiploic vein in response to the intragastric administration of 1N HCl were also normal. The SLI contents and the characteristics in molecular size of tissue extracts from the cysteamine dogs were similar to those of normal dogs. Thus, it is concluded that cysteamine has no specific effect on canine splanchnic D-cells.

Administration, Oral↗
PubMed2000

Inhibitory effects of WR-2721 and cysteamine on tumor initiation in mammary glands of pregnant rats by radiation.

We evaluated the effect of WR-2721 [S-2-(3-aminopropylamino)-ethylphosphorothioic acid] and cysteamine (2-mercaptoethylamine) on the development of radiation-induced mammary tumors in rats. Pregnant rats were treated with WR-2721 or cysteamine 30 min prior to whole-body irradiation with gamma rays from a (60)Co source at a dose of 1.5 or 2.6 Gy. Additional pregnant rats were given saline and then exposed to gamma rays at a dose of 0, 1.5 or 2.6 Gy as a control. All rats were implanted with pellets of diethylstilbestrol, a tumor promoter, 1 month after termination of nursing and were observed for 1 year to detect palpable mammary tumors. No mammary tumors developed in the saline-injected nonirradiated rats. However, when rats were irradiated with 1.5 or 2. 6 Gy after saline treatment, the incidence of mammary tumors was high (71.4 and 92.3%, respectively). Administration of WR-2721 or cysteamine prior to irradiation with 1.5 Gy significantly decreased the tumor incidence (23.8 and 20.8%, respectively). Tumor prevention by either agent was less effective at the higher dose. The appearance of the first mammary tumor occurred later in rats treated with WR-2721 or cysteamine than in the control rats. An increasing rate of adenocarcinoma in the control group was observed with increasing dose from 1.5 Gy up to 2.6 Gy. However, the development of adenocarcinoma did not increase after pretreatment with WR-2721 or cysteamine in rats irradiated with 2.6 Gy. Many of the mammary tumors that developed in the control rats were of the ER(+)PgR(+) type. Administration of WR-2721 produced no tumors of the ER(+)PgR(+) type. Cysteamine treatment increased the development of ER-negative tumors. The serum concentration of progesterone was significantly higher in rats treated with WR-2721 or cysteamine than in the control rats. On the other hand, the estradiol-17beta concentration was reduced by treatment with WR-2721, but not significantly compared to the control. WR-2721 and cysteamine had no effect on the prolactin concentration of the irradiated rats. The results suggest that administration of WR-2721 or cysteamine prior to the irradiation has a potent preventive effect on theinitiation phase during mammary tumorigenesis.

Adenocarcinoma↗
PubMed1981

Brunner's glands of the rat during cysteamine ulceration.

Duodenal ulcers can be produced in rats by subcutaneous administration of cysteamine-HCl. The pathogenesis of these ulcers has not been fully explained. Increased acid secretion is necessary but not sufficient for ulcer production. In the present study we have observed pronounced alterations in the histologic appearance of the duodenal glands of Brunner during ulcer formation. The secretory cells became extremely flattened without mucus content and the lumina of the acini dilated. Changes became most pronounced between 4 and 8 h after administration of cysteamine. Repeated injections of pentagastrin in a dosage inducing an acid response equivalent to the one induced by cysteamine did not produce any histologic changes in Brunner's glands or any ulcerations. When cysteamine was administered to rats with chronic gastric fistulas draining the gastric secretions, no duodenal ulcerations were produced, but Brunner's glands still became depleted of mucus. These findings suggest that the histologic changes in Brunner's glands are not secondary either to the increased acid secretion induced by cysteamine or to ulcer formation. Together with our previous demonstration of a marked reduction duodenal secretion in the first 10 h after cysteamine administration, the results of the present study suggest an inhibitory effect of cysteamine on the synthetic activity of Brunner's glands rather than an impaired release mechanism. The effect of cysteamine on Brunner's glands may be an important factor in the pathogenesis of cysteamine-induced duodenal ulceration.

Animals↗
PubMed1982

Role of delayed gastric emptying in the pathogenesis of cysteamine-induced duodenal ulcer in the rat.

Cysteamine is a potent duodenal ulcerogen in rats. It has been demonstrated to inhibit gastric empyting, whose role in ulcer formation is unknown. In the present study the effect of cysteamine on gastric motility and emptying rate in rats was studied by direct fluoroscopic observation. The delayed gastric empyting was due to a pronounced relaxation of the stomach and a complete blocking of gastric peristalsis. These effects have their maximum within the first 4 h after administration of cysteamine. Thereafter peristalsis and gastric empyting slowly return. In controls contrast medium administered intragastrically was completely discharged from the stomach within 30 min. After cysteamine the first small amounts of contrast medium were discharged into the duodenum after 4 h, and contrast medium remained in the stomach for at least 12 h after administration. The size of the stomach reached a maximum after 3 h and approached normal values again after 12 h. Because of complete gastric retention the acid gastric secretions provoked by cysteamine probably accumulate in the stomach during the first 4 h after cysteamine administration, and because of the absence of peristalsis they are not mixed with gastric contents. After 4 h this pool of undiluted gastric secretions gradually is emptied into the duodenum, where the mucosal resistance is reduced by inhibition of the secretory activity of Brunner's glands, and ulceration rapidly develops. The time relationship is supported by histopathologic findings and measurements of gastric acid secretions after cysteamine. Vagotomy augmented the inhibitory effect of cysteamine on gastric motility. The relaxation was even more pronounced, and contrast medium was not discharged from the stomach within 24 h. In these rats cysteamine induced ulcerations in the stomach.

Animals↗
PubMed1990

Attenuating effect of bromocriptine on cysteamine anticarcinogenesis of stomach cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine.

The effect of bromocriptine on inhibition by cysteamine of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine was investigated in inbred Wistar rats. After 25 weeks of p.o. treatment with N-methyl-N'-nitro-N-nitrosoguanidine, rats were given injections every other day: cysteamine (50 mg/kg body weight); cysteamine (50 mg/kg body weight) plus bromocriptine (0.5 or 0.25 mg/kg body weight); or bromocriptine (0.5 or 0.25 mg/kg body weight). In week 52, the group treated with cysteamine showed a significantly decreased incidence of gastric cancers. Concomitant treatment with bromocriptine at 0.5 but not at 0.25 mg/kg body weight significantly attenuated the inhibitory effect of cysteamine on gastric carcinogenesis. Administration of bromocriptine alone at either dosage had no influence on gastric carcinogenesis. The labeling index of the antral mucosa was significantly reduced in rats treated with cysteamine and significantly higher in those treated concomitantly with bromocriptine at 0.5 mg/kg body weight than in those treated with cysteamine alone. These findings indicate that cysteamine suppressed gastric carcinogenesis and that bromocriptine at high dosage attenuated this inhibition. These findings also suggest that dopamine is involved in the mechanism of inhibition of gastric carcinogenesis by cysteamine.

Animals↗
PubMedDate not supplied

Evaluation of the reproductive and developmental safety of cysteamine in the rat: effects on female reproduction and early embryonic development.

Cystinosis is an autosomal recessive metabolic disease in which the amino acid cystine accumulates in lysosomes due to a defect in lysosomal cystine transport. Cystinosis in infancy is associated with poor growth, muscle wastage, and death at about age 10 due to kidney failure. Treatment with cysteamine and kidney transplantation enables cystinotic girls to reach reproductive age and to be healthy enough to permit pregnancy. It is not known whether exposure to cysteamine will have adverse effects on reproduction in the human. It is also possible that some of the complications seen in cystinotic children could be avoided if a pregnant woman carrying a cystinotic fetus were given cysteamine. However, this treatment is not likely to occur until therapeutic exposures to cysteamine are judged to present no increased risk to the human fetus. As part of a larger investigation assessing the reproductive and developmental safety of cysteamine (as phosphocysteamine) using the rat, the two studies reported herein were performed. The first, a dose-finding study, led to the selection of 150 mg/kg/day as the highest dose of cysteamine used for the second and primary focus of this report. The second study involved the exposure of female rats to cysteamine from premating through day 6.5 postconception and assessment of female fertility and early embryonic development. Cysteamine was administered orally in doses of 0, 37.5, 75, 100, or 150 mg/kg/day. There were no clinical signs of maternal toxicity during the exposures of 2 to 5 weeks before successful mating. Animals in the 150 mg/kg/day group experienced a nonsignificant decrease in body weight gain during pregnancy to day 6.5 postconception, a significant increase in liver and spleen weights, and a significant increase in days to coitus--suggesting that a low level of toxicity was manifested. However, there were no adverse effects on reproductive performance with respect to conception and early embryonic development.

Animals↗
PubMed1989

Cysteamine and the endocrine pancreas: immunocytochemical, immunochemical, and functional aspects.

To evaluate the previously reported depletion of pancreatic somatostatin by cysteamine (beta-mercaptoethylamine), mice were injected subcutaneously with the drug at 300 mg/kg. Immunocytochemical analysis performed on sections from tissue taken at 4 h after the injection revealed an elimination of somatostatin-14-like immunoreactivity without alterations in the somatostatin-28(1-12)-like immunoreactivity. In sections from tissues taken at 24 h after injection, no differences between cysteamine-injected animals and controls were observed. Immunochemical analysis of somatostatin-14-like immunoreactivity in pancreatic extracts showed a significant reduction of the concentration (P less than 0.001). In contrast, no change in the insulin concentration was observed. Functionally, cysteamine lowered the plasma glucose levels at 1 h after injection; this effect persisted for 6 h. Plasma insulin levels were likewise reduced transiently by cysteamine. Concomitant administration of somatostatin did not influence these effects of cysteamine. The plasma glucose-lowering effect of cysteamine was seen also in alloxan-diabetic mice. We conclude that cysteamine alters the immunoreactive characteristics of pancreatic somatostatin without affecting the immunoreactivity of insulin, and that cysteamine transiently reduces plasma glucose and insulin levels.

Animals↗
PubMed1986

Synthesis and antineoplastic activity of CNC-cysteamine and related compounds.

N'-[N-(2-Chloroethyl)-N-nitroso]carbamoyl cysteamine (CNC-cysteamine) and several related compounds have been synthesized and tested against L 1210 leukemia in mice. Reaction of N-(2-chloroethyl)-N-nitrosocarbamoyl azide (CNC-azide) with cysteamine yielded CNC-cysteamine and bis(CNC)cystamine. Reaction of CNC-azide with cystamine in the presence of triethylamine gave bis(CNC)cystamine. Unexpectedly, formation of CNC-cystamine carboxylazide as a minor reaction product was also observed. N-(2-Chloroethyl)carbamoyl cysteamine 2-chloroethylcarbamate was formed when 2-chloroethyl isocyanate was reacted with cysteamine. Nitrosation of this cysteamine N,S-dicarbamoyl derivative led to formation of a mixture of two dinitroso isomers. Preliminary testing of the newly synthesized CNC-derivatives against L 1210 leukemia in mice revealed that CNC-cysteamine, its disulfide bis(CNC)cystamine and CNC-cystamine carboxylazide were highly active against L 1210 leukemia.

Animals↗
PubMed2005

Strict cysteamine dose regimen is required to prevent nocturnal cystine accumulation in cystinosis.

Cystinosis is an autosomal recessive disorder, caused by mutations in the lysosomal cystine carrier cystinosin, encoded by the CTNS gene. The disease generally manifests with Fanconi syndrome during the first year of life and progresses towards end stage renal disease before the age of 10 years. Cysteamine depletes intralysosomal cystine content, postpones the deterioration of renal function and the occurrence of extra-renal organ damage. Based on the pharmacokinetic data, patients with cystinosis are advised to use cysteamine every 6 h. The aim of this study was (1) to evaluate the cysteamine dose regimen in Dutch patients with cystinosis and (2) to determine morning polymorphonuclear (PMN) leukocyte cystine content 6 h vs 9 h after the last evening cysteamine dose. Only 5/22 of Dutch cystinosis patients ingested cysteamine every 6 h. Morning (8 a.m.) PMN cystine content in 11 examined patients was elevated 9 h after 12.5-15 mg/kg evening cysteamine dose compared to the value 6 h after the ingestion of the same dose (0.73+/-0.81 nmol vs 0.44+/-0.52 nmol cystine/mg protein, p =0.02). In conclusion, only the minority of Dutch cystinosis patients follows the recommended strict cysteamine dose regimen. We provide evidence that cysteamine has to be administered every 6 h, including the night, as it has much better effect for maintaining low PMN cystine levels.

Adolescent↗
PubMed1999

Effects of pre- and postnatal cysteamine exposure on renal function in the rat.

The safety of cysteamine after renal transplantation and during pregnancy is an important issue, since girls with cystinosis are in better health on cysteamine therapy and thus more likely to become pregnant. In the first study, cysteamine was given to pregnant rats on days 6.5-18.5 post conception in oral doses of 0, 37.5, 75, 100, and 150 mg/kg per day. The dams were sacrificed on day 20.5, the fetal kidneys removed and prepared for histological examination. In the second study, cysteamine was given to dams on days 6.5-19.5 post conception in oral doses of 0, 37.5, 50, and 75 mg/kg per day. Dams were allowed to give birth naturally and pups were given cysteamine on days 4-21 to yield the same oral doses of cysteamine given to the dam. Renal function was evaluated on day 35. Histological examination of fetal kidneys revealed no changes even in kidneys from fetuses with growth retardation and malformations. Furthermore, there were no alterations in renal function in offspring on day 35. These findings demonstrate that cysteamine therapy does not affect renal development in the rat. Further investigations will be required to prove whether cysteamine therapy has the potential to affect renal development in the human.

Animals↗