Biomedical subjects

R J Reiter

Publications and source records attributed to R J Reiter.

At least 91 records · Page 5Linked to original sources

PubMed2000

Circadian rhythm abnormalities of melatonin in Smith-Magenis syndrome.

BACKGROUND: Smith-Magenis syndrome (SMS) is a multiple congenital anomalies/mental retardation syndrome associated with a hemizygous deletion of chromosome 17, band p11.2. Characteristic features include neurobehavioural abnormalities such as aggressive and self-injurious behaviour and significant sleep disturbances. The majority of patients have a common deletion characterised at the molecular level. Physical mapping studies indicate that all patients with the common deletion are haploinsufficient for subunit 3 of the COP9 signalosome (COPS3), which is conserved from plants to humans, and in the plant Arabidopis thaliana regulates gene transcription in response to light. Haploinsufficiency of this gene is hypothesised to be potentially involved in the sleep disturbances seen in these patients. Melatonin is a hormone secreted by the pineal gland. SMS patients are reported to have fewer sleep disturbances when given a night time dose of this sleep inducing hormone. METHODS: Urinary excretion of 6-sulphatoxymelatonin (aMT6s), the major hepatic metabolite of melatonin, in 19 SMS patients were measured in conjunction with 24 hour sleep studies in 28 SMS patients. Five of the 28 patients did not have the common SMS deletion. To investigate a potential correlation of COPS3 haploinsufficiency and disturbed melatonin excretion, we performed fluorescence in situ hybridisation (FISH) using two BACs containing coding exons of COPS3. RESULTS: All SMS patients show significant sleep disturbances when assessed by objective criteria. Abnormalities in the circadian rhythm of aMT6s were observed in all but one SMS patient. Interestingly this patient did not have the common deletion. All patients studied, including the one patient with a normal melatonin rhythm, were haploinsufficient for COPS3. CONCLUSIONS: Our data indicate a disturbed circadian rhythm in melatonin and document the disturbed sleep pattern in Smith-Magenis syndrome. Our findings suggest that the abnormalities in the circadian rhythm of melatonin and altered sleep patterns could be secondary to aberrations in the production, secretion, distribution, or metabolism of melatonin; however, a direct role for COPS3 could not be established.

Abnormalities, Multiple↗

PubMed2000

Antioxidative effects of melatonin in protection against cellular damage caused by ionizing radiation.

Ionizing radiation is classified as a potent carcinogen, and its injury to living cells is, to a large extent, due to oxidative stress. The molecule most often reported to be damaged by ionizing radiation is DNA. Hydroxyl radicals (*OH), considered the most damaging of all free radicals generated in organisms, are often responsible for DNA damage caused by ionizing radiation. Melatonin, N-acetyl-5-methoxytryptamine, is a well-known antioxidant that protects DNA, lipids, and proteins from free-radical damage. The indoleamine manifests its antioxidative properties by stimulating the activities of antioxidant enzymes and scavenging free radicals directly or indirectly. Among known antioxidants, melatonin is a highly effective scavenger of *OH. Melatonin is distributed ubiquitously in organisms and, as far as is known, in all cellular compartments, and it quickly passes through all biological membranes. The protective effects of melatonin against oxidative stress caused by ionizing radiation have been documented in in vitro and in vivo studies in different species and in in vitro experiments that used human tissues, as well as when melatonin was given to humans and then tissues collected and subjected to ionizing radiation. The radioprotective effects of melatonin against cellular damage caused by oxidative stress and its low toxicity make this molecule a potential supplement in the treatment or co-treatment in situations where the effects of ionizing radiation are to be minimized.

Animals↗

PubMed2000

Chromium(III)-induced 8-hydroxydeoxyguanosine in DNA and its reduction by antioxidants: comparative effects of melatonin, ascorbate, and vitamin E.

Chromium compounds are well documented carcinogens. Cr(III) is more reactive than Cr(VI) toward DNA under in vitro conditions. In the present study, we investigated the ability of Cr(III) to induce oxidative DNA damage by examining the formation of 8-hydroxydeoxyguanosine (8-OH-dG) in calf thymus DNA incubated with CrCl(3) plus H(2)O(2). We measured 8-OH-dG using HPLC with electrochemical detection. In the presence of H(2)O(2), we observed that Cr(III)-induced formation of 8-OH-dG in isolated DNA was dose and time dependent. Melatonin, ascorbate, and vitamin E (Trolox), all of which are free radical scavengers, markedly inhibited the formation of 8-OH-dG in a concentration-dependent manner. The concentration that reduced DNA damage by 50% was 0.51, 30.4, and 36.2 microM for melatonin, ascorbate, and Trolox, respectively. The results show that melatonin is 60- and 70-fold more effective than ascorbate or vitamin E, respectively, in reducing oxidative DNA damage in this in vitro model. These findings also are consistent with the conclusion that the carcinogenic mechanism of Cr(III) is possibly due to Cr(III)-mediated Fenton-type reactions and that melatonin's highly protective effects against Cr(III) relate, at least in part, to its direct hydroxyl radical scavenging ability.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2000

Changes in lipid peroxidation during pregnancy and after delivery in rats: effect of pinealectomy.

Pregnancy is a physiological state accompanied by a high energy demand of many bodily functions and an increased oxygen requirement. Because of the increased intake and utilization of oxygen, increased levels of oxidative stress would be expected. In the present study, the degree of lipid peroxidation was examined in different tissues from non-pregnant and pregnant rats after the delivery of their young. Melatonin and other indole metabolites are known to be direct free radical scavengers and indirect antioxidants. Thus the effect of pinealectomy at 1 month before pregnancy on the accumulation of lipid damage was investigated in non-pregnant and pregnant rats after the delivery of their young. Malonaldehyde and 4-hydroxyalkenal concentrations were measured in the lung, uterus, liver, brain, kidney, thymus and spleen from intact and pinealectomized pregnant rats soon after birth of their young and at 14 and 21 days after delivery. The same parameters were also evaluated in intact and pinealectomized non-pregnant rats. Shortly after delivery, lipid oxidative damage was increased in lung, uterus, brain, kidney and thymus of the mothers. No differences were detected in liver and spleen. Pinealectomy enhanced this effect in the uterus and lung. It is concluded that during pregnancy high levels of oxidative stress induce an increase in oxidative damage to lipids, which in some cases is inhibited by the antioxidative actions of pineal indoles.

Analysis of Variance↗

PubMed1999

Inhibitory effects of melatonin on ferric nitrilotriacetate-induced lipid peroxidation and oxidative DNA damage in the rat kidney.

Ferric nitrilotriacetate (Fe-NTA) is a known complete renal carcinogen which induces lipid peroxidation and oxidative DNA damage in rat kidney. In this study, the in vivo and in vitro effects of melatonin on Fe-NTA-induced lipid and oxidative DNA damage were determined. The levels of malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) were assayed as an index of lipid peroxidation and the levels of 8-hydroxydeoxyguanosine (8-OH-dG) as an endpoint of oxidative DNA damage. In in vitro studies, the increased levels of MDA and 4-HDA induced by Fe-NTA were observed to be dose-dependent and time-dependent. The increase in lipid peroxidation was inhibited by melatonin in a concentration-dependent manner. When Fe-NTA(15 mg Fe/kg body weight) was intraperitoneally injected into rats, the levels of MDA + 4-HDA and 8-OH-dG in the rat kidney were increased 1 h after its administration as compared to levels of these constituents in the control group. Pretreatment with melatonin (25 mg/kg or 50 mg/kg) 30 min before the Fe-NTA injection resulted in a significant reduction in the levels of lipid peroxidation and 8-OH-dG induced by Fe-NTA in the rat kidney. These results are consistent with the conclusion that the toxicity of Fe-NTA is due to the generation of reactive oxygen species and that melatonin's protective effects relate to its direct radical scavenging ability and due to other antioxidative processes induced by the indole.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1999

High physiological levels of melatonin in the bile of mammals.

Bile is an important physiological bodily fluid which functions in the regulation of cholesterol metabolism, promotes the absorption of lipid and fat-soluble vitamins by the gut and serves in the excretion of toxic substances from the liver. Conversely, due to autooxidative processes bile is highly toxic to the hepatocyte and gastrointestinal epithelium. In this investigation, extremely high day time physiological levels of the endogenous antioxidant, melatonin, were measured in the bile of several mammals including rat, guinea pig, rabbit, pig, monkey and humans. Melatonin concentrations in the bile samples ranged from 2,000 to 11,000 pg/ml when measured by radioimmunoassay (RIA). These melatonin levels in bile are 2 to 3 orders of magnitude higher than those in day time serum. The presence of melatonin in bile was confirmed by HPLC with an electrochemical detector. This method, like the RIA, also documented very high levels of melatonin in bile. The presence of high levels of melatonin in bile may be essential to prevent oxidative damage to biliary and small intestinal epithelium induced by bile acids and oxidized cholesterol derivatives.

Adult↗

PubMed1999

Augmentation of indices of oxidative damage in life-long melatonin-deficient rats.

The chief pineal secretory product, melatonin, is an efficient free radical scavenger and antioxidant. The current study tested whether the life-long reduction of endogenous melatonin levels due to pinealectomy would influence the accumulation of oxidatively damaged products as the animals aged. Rats were either pinealectomized or sham operated when they were 2-months-old. At 25 months of age these animals were killed along with 2-month-old controls. Aging in the pineal-intact animals was associated with increased levels of lipid peroxidation products (malondialdehyde and 4-hydroxyalkenals in the lung, kidney and skin), rises in an oxidatively damaged DNA product (8-hydroxy-deoxyguanosine in liver, kidney and pancreas), and in the levels of protein carbonyls (in the liver). Likewise, advanced age was associated with a significant decrease in membrane fluidity (increased membrane rigidity) of hepatic microsomes in pineal-intact rats. For all of these parameters and in a number of organs, pinealectomy caused further increases in the indices of oxidative damage. Consistent with previous suggestions, the implications of these findings is that aging is associated with the augmented accumulation of oxidatively damaged macromolecules and that these increases are exaggerated when a relative melatonin deficiency is induced by pinealectomy. The findings are consistent with the idea that the accelerated accumulation of oxidatively damaged products after pinealectomy was due to reduction in melatonin since it functions as a free radical scavenger and antioxidant. On the other hand, other pineal secretory products that were reduced as a consequence of pineal removal may have also been responsible for some of the observed changes.

Aging↗

PubMed1999

Identification of highly elevated levels of melatonin in bone marrow: its origin and significance.

Bone marrow is an important tissue in generation of immunocompetent and peripheral blood cells. The progenitors of hematopoietic cells in bone marrow exhibit continuous proliferation and differentiation and they are highly vulnerable to acute or chronic oxidative stress. In this investigation, highly elevated levels of the antioxidant melatonin were identified in rat bone marrow using immunocytochemistry, radioimmunoassay, high performance liquid chromatography with electrochemical detection and mass spectrometry. Night-time melatonin concentrations (expressed as pg melatonin/mg protein) in the bone marrow of rats were roughly two orders of magnitude higher than those in peripheral blood. Measurement of the activities of the two enzymes (N-acetyltransferase (NAT) and hydroxyindole-O-methoxyltransferase (HIOMT)) which synthesize melatonin from serotonin showed that bone marrow cells have measurable NAT activity, but they have very low levels of HIOMT activity (at the one time they were measured). From these studies we could not definitively determine whether melatonin was produced in bone marrow cells or elsewhere. To investigate the potential pineal origin of bone marrow melatonin, long-term (8-month) pinealectomized rats were used to ascertain if the pineal gland is the primary source of this antioxidant. The bone marrow of pinealectomized rats, however, still exhibited high levels of melatonin. These results indicate that a major portion of the bone marrow's melatonin is of extrapineal origin. Immunocytochemistry clearly showed a positive melatonin reaction intracellularly in bone marrow cells. A melatonin concentrating mechanism in these cells is suggested by these findings and this may involve a specific melatonin binding protein. Since melatonin is an endogenous free radical scavenger and an immune-enhancing agent, the high levels of melatonin in bone marrow cells may provide on-site protection to reduce oxidative damage to these highly vulnerable hematopoietic cells and may enhance the immune capacity of cells such as lymphocytes.

Acetylserotonin O-Methyltransferase↗

PubMed1999

Melatonin and protection from whole-body irradiation: survival studies in mice.

The radioprotective ability of melatonin was investigated in mice exposed to an acute whole-body gamma radiation dose of 815 cGy (estimated LD50/30 dose). The animals were observed for mortality over a period of 30 days following irradiation. The results indicated 100% survival for unirradiated and untreated control mice, and for mice treated with melatonin or solvent alone. Forty-five percent of mice exposed to 815 cGy radiation alone, and 50% of mice pretreated with solvent and irradiated with 815 cGy were alive at the end of 30 days. Irradiated mice which were pretreated with 125 mg/kg melatonin exhibited a slight increase in their survival (60%) (p=0.3421). In contrast, 85% of irradiated mice which were pretreated with 250 mg/kg melatonin were alive at the end of 30 days (p=0.0080). These results indicate that melatonin (at a dose as high as 250 mg/kg) is non-toxic, and that high doses of melatonin are effective in protecting mice from lethal effects of acute whole-body irradiation.

Animals↗

PubMed1999

Melatonin and tryptophan derivatives as free radical scavengers and antioxidants.

Several tryptophan derivatives function as free radical scavengers and antioxidants. The molecule that has been most widely investigated in this regard is N-acetyl-5-methoxytryptamine (melatonin); however, pinoline (6-methoxy-1,2,3,4-tetrahydro-beta-carboline) and N-acetylserotonin also possess free radical scavenging activity. Experimental studies have shown that melatonin directly scavenges the hydroxy radical, peroxyl radical, peroxynitrite anion, and singlet oxygen. Furthermore, this tryptophan derivative stimulates a number of antioxidative enzymes and stabilizes cell membranes; this latter action helps membranes to resist free radical damage. While the antioxidative actions of most molecules are limited by their specific intracellular distribution, e.g., vitamin E in lipid-rich membranes, melatonin's antioxidative actions include the protection of lipids in the cell membrane, proteins in the cytosol, and DNA in the nucleus. Furthermore, melatonin crosses all morphophysiological barriers and enters equally well all cells in the organism.

Animals↗

PubMed1999

Melatonin in relation to the antioxidative defense and immune systems: possible implications for cell and organ transplantation.

Melatonin, a molecule synthesized and secreted by the mammalian (including human) pineal gland, has a variety of seemingly unrelated functions in organisms. In photoperiodically-dependent seasonal breeders, the changing melatonin signal imparts seasonal information to the species thereby regulating the annual cycle of reproduction Melatonin also is involved in a number of 24 h rhythms and is believed to be an important component of the circadian system. More recently, melatonin was found to relate to immune function in organisms and to be an effective antioxidant. As an antioxidant melatonin would appear to provide substantial protection against free radicals which are generated under a variety of experimental corrections, including ischemia/reperfusion injury. These latter two functions of melatonin, i.e., as an immune system modulator and as an antioxidant, both may have applicability to cell and organ transplantation.

Animals↗

PubMed1999

Effects of melatonin on the Harderian gland of lipopolysaccharide-treated rats: morphological observations.

Melatonin is a free radical scavenger and antioxidant. This indol is reported to efficiently scavenge both hydroxyl and peroxyl radicals and it also reduces both in vitro and in vivo tissue damage due to oxidants which generate oxygen toxic radicals. Lipopolysaccharide (LPS) administration induces oxidative damage in various tissues mainly due to its ability to increase reactive oxygen species. In the present work, we studied the morphological changes and lipid peroxidation in the Harderian gland after LPS administration and the effects of melatonin in preventing the induced changes. Hyperchromasia, vesicular degeneration, necrosis and infiltration with macrophages, monocytes and neutrophils were observed in the LPS-treated group (10 mg/kg, intraperitonally [i.p.]). Also, a typical structure of the glandular acini of the gland exhibited diffuse damage. In the LPS rats treated with melatonin (10 mg/kg, i.p.), a diminished number of infiltrative cells was seen, and cloudy swelling was reduced, as was nuclear hyperchromasia. Neither necrosis nor vesicular degeneration were noted in the melatonin-treated rats, and in general, glandular structure was preserved. Lipid peroxidation products increased significantly within six hours after LPS administration, and melatonin treatment decreased the LPS-dependent lipid peroxidation products. These data together suggest that melatonin protects the Harderian gland against LPS toxicity in terms of morphological damage.

Animals↗

PubMed1999

Role of pinoline and melatonin in stabilizing hepatic microsomal membranes against oxidative stress.

We investigated the influence of pinoline (0.01-1.5 mM) on microsomal membrane fluidity before and after rigidity was induced by oxidative stress. In addition, we tested the effect of pinoline in the presence of 1 mM melatonin. The fluidity in rat hepatic microsomes was monitored using fluorescence spectroscopy and it was compared to the inhibition of malonaldehyde (MDA) plus 4-hydroxyalkenals (4-HDA) production as a reflection of lipid peroxidation. Below 0.6 mM, pinoline inhibited membrane rigidity in a manner parallel to its inhibitory effect on MDA + 4-HDA formation. At concentrations between 1-1.5 mM, pinoline was less effective in stabilizing microsomal membranes than was predicted from its inhibition of lipid peroxidation. The addition of 1 mM melatonin enhanced the membrane-stabilizing activity of pinoline (0.01-0.6 mM). This cooperative effect was not observed for concentrations of pinoline between 1-1.5 mM. When pinoline was tested without induced oxidative damage, 1-1.5 mM pinoline maintained membrane fluidity at the same level as that recorded after induced lipid peroxidation. The results suggest that pinoline may be another pineal molecule that prevents membrane rigidity mediated by lipid peroxidation and this ability is enhanced by melatonin.

Aldehydes↗

PubMed1999

Melatonin reduces lipid peroxidation and tissue edema in cerulein-induced acute pancreatitis in rats.

Since oxygen free radicals and lipid peroxidation have been implicated in the pathogenesis of an early stage of acute pancreatitis, we examined whether melatonin, a recently discovered free-radical scavenger, could attenuate pancreatic injury in Sprague-Dawley rats with cerulein-induced pancreatitis. Acute pancreatitis was induced by four intraperitoneal injections of cerulein (50 microg/kg body wt) given at 1-hr intervals. Thirty minutes after the last cerulein injection, the rats were killed and the degree of pancreatic edema, the level of lipid peroxidation in the pancreas, and serum amylase activity were increased significantly. Pretreatment with melatonin (10 or 50 mg/kg body wt) 30 min before each cerulein injection resulted in a significant reduction in pancreatic edema and the levels of lipid peroxidation. Serum amylase activity, however, was not significantly influenced by either dose of melatonin. Moreover, we found that cerulein administration was associated with stomach edema as well as high levels of lipid peroxidation in the stomach and small intestine, which were also reduced by melatonin. Melatonin's protective effects in cerulein-treated rats presumably relate to its radical scavenging ability and to other antioxidative processes induced by melatonin.

Acute Disease↗

PubMed1999

Melatonin regulates glucocorticoid receptor: an answer to its antiapoptotic action in thymus.

We have previouslyreported that low doses of melatonin inhibit apoptosis in both dexamethasone-treated cultured thymocytes (standard model for the study of apoptosis) and the intact thymus. Here we elucidate the mechanism by which this agent protects thymocytes from cell death induced by glucocorticoids. Our results demonstrate an effect of melatonin on the mRNA for antioxidant enzymes in thymocytes, also showing an unexpected regulation by dexamethasone of these mRNA. Both an effect of melatonin on the general machinery of apoptosis and a possible regulation of the expression of the cell death related genes bcl-2 and p53 are shown not to be involved. We found melatonin to down-regulate the mRNA for the glucocorticoid receptor in thymocytes (glucocorticoids up-regulate their own receptor). The decrease by melatonin of mRNA levels for this receptor in IM-9 cells (where glucocorticoids down-regulate it) demonstrates that melatonin actually down-regulates glucocorticoid receptor. These findings allow us to propose the effects of melatonin on this receptor as the likely mediator of its thymocyte protection against dexamethasone-induced cell death. This effect of melatonin, given the oxidant properties of glucocorticoids, adds another mechanism to explain its antioxidant effects.

Animals↗

PubMed1999

The protective role of endogenous melatonin in carrageenan-induced pleurisy in the rat.

Peroxynitrite, a potent cytotoxic oxidant formed by the reaction of nitric oxide (NO) with the superoxide anion, was recently proposed to play a major pathogenic role in the inflammatory process. Here we have investigated the effects of endogenous melatonin, a known scavenger of peroxynitrite, in rats subjected to carrageenan-induced pleurisy. Endogenous melatonin was depleted in rats maintained on 24 h light cycle for 1 wk. In vivo depletion of endogenous melatonin enhanced the carrageenan-induced degree of pleural exudation and polymorphonuclear leukocyte migration in rats subjected to carrageenan-induced pleurisy. Lung myeloperoxidase activity and lipid peroxidation were significantly increased in melatonin-deprived rats. However, the inducible NO synthase in lung samples was unaffected by melatonin depletion. Immunohistochemical analysis for nitrotyrosine revealed a positive staining in lungs from carrageenan-treated rats that was markedly enhanced in melatonin-deprived rats. Furthermore, melatonin depletion significantly increased peroxynitrite formation as measured by the oxidation of the fluorescent dye dihydrorhodamine 123, enhanced DNA damage and the decrease in mitochondrial respiration and reduced the cellular levels of NAD+ in macrophages harvested from the pleural cavity of rats subjected to carrageenan-induced pleurisy. In vivo treatment with exogenous melatonin (15 mg/kg intraperitoneal) significantly reversed the effects of melatonin depletion. Thus, endogenous melatonin plays an important protective role against carrageenan-induced local inflammation.

Animals↗

PubMed1999

Role of melatonin in reduction of lipid peroxidation and peroxynitrite formation in non-septic shock induced by zymosan.

Zymosan, a non-bacterial agent, causes inflammation by inducing the production of a variety of cytokines and pro-inflammatory mediators, wherein reactive oxygen species including nitric oxide and peroxynitrite are known to play a crucial role in the inflammatory process. The current study was designed to investigate the protective effect of melatonin, a radical scavenger and antioxidant, on non-septic shock induced by zymosan in the rat. Four groups of rats (controls, melatonin-injected [5 mg/kg x 6], zymosan-injected [500 mg/kg], and zymosan + melatonin) were used in this experiment. Thiobarbituric acid reactive substances (malondialdehyde [MDA] + 4-hydroxyalkenals [4-HDA]), as an index of lipid peroxidation, were measured in the liver, lung, small intestine (ileum), kidney and pancreas. Twenty-four hours after zymosan administration, MDA + 4-HDA levels were significantly increased in the liver, lung, small intestine, and kidney while the increase in the pancreas was not statistically significant compared to levels in control rats. The percentage increases in lipid peroxidation products were 34.3%, 39.2%, 48.5%, 32.5%, and 17.4% for the liver, lung, small intestine, kidney, and pancreas, respectively. In animals given melatonin 30 minutes before zymosan, and 5 more times after zymosan (i.e., every 4 hours), the increase in MDA + 4-HDA levels was reduced in all organs studied. There was also a significant increase in the volume of peritoneal exudate in zymosan-treated rats that was reduced when the zymosan-shocked rats received melatonin. After zymosan administration, immunohistochemical and histological examination demonstrated a marked increase in the immunoreactivity to nitrotyrosine, a specific "footprint" of peroxynitrite, and tissue damage in the liver, lung, and small intestine of zymosan-shocked rats. Again, melatonin treatment reduced both nitrotyrosine immunoreactivity and tissue damage associated with zymosan administration.

Animals↗

PubMed1999

Pharmacological aspects of N-acetyl-5-methoxytryptamine (melatonin) and 6-methoxy-1,2,3,4-tetrahydro-beta-carboline (pinoline) as antioxidants: reduction of oxidative damage in brain region homogenates.

Oxygen consumption is a necessity for all aerobic organisms, but oxygen is also a toxic molecule that leads to the generation of free radicals. The brain consumes a high percentage of the oxygen inhaled (18.5%), and it contains large amounts of unsaturated fatty acids, which makes it highly susceptible to lipid peroxidation. Melatonin (N-acetyl-5-methoxytryptamine), the main secretory product of the pineal gland, is a free radical scavenger that was found to protect against lipid peroxidation in many experimental models. Another compound found in the pineal gland is pinoline (6-methoxy-1,2,3,4-tetrahydro-beta-carboline). Pinoline is structurally related to melatonin. Evidence suggests that pinoline may have an antioxidant capacity similar to that of melatonin. In this study, the ability of pinoline to protect against H2O2-induced lipid peroxidation of different rat brain homogenates (frontal cortex, striatum, cerebellum, hippocampus, and hypothalamus) was investigated. The degree of lipid peroxidation was assessed by estimating the levels of thiobarbituric acid reactive substances, malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA). Pinoline's antioxidant capacity was compared with that of melatonin. Both melatonin and pinoline reduced the level of MDA and 4-HDA in a dose-dependent manner in all brain regions tested. To compare the antioxidant capacities, percent-inhibition curves were created, and the IC50 values were calculated. The IC50 values for melatonin were higher in all brain regions than were those for pinoline. The IC50 values for melatonin in the five different brain regions ranged from 0.16 mM-0.66 mM, and for pinoline, they ranged from 0.04 mM-0.13 mM. The possibility of synergistic interactions between melatonin and pinoline were also determined using the method of Berenbaum. Little evidence for either synergistic, additive, or antagonistic interactions between melatonin and pinoline was found.

Animals↗