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The in vivo effect of melatonin on paraquat-induced oxidative damage in rat lung and liver was studied using two parameters: the concentration of malonaldehyde and 4-hydroxyalkenals as indices of lipid peroxidation; changes in total and oxidized glutathione. Melatonin (10 mg/kg) or an equal volume of saline were administered intraperitoneally (ip) to rats 30 min prior to an ip injection of paraquat (20 mg/kg or 70 mg/kg). After paraquat treatment, the animals received melatonin or saline ip injections every six hours for 24 hours. Rats were killed 24 hours after paraquat injection. In lung, both the low and high dose of paraquat, when administered with saline, augmented lipid peroxidation (100% and 18%, respectively) above levels found in control animals. Treatment with melatonin completely reversed this effect. In liver, paraquat (70 mg/kg) increased lipid peroxidation by 40% over the levels of control animals. The increase was completely abolished by treatment with melatonin. Paraquat at 20 mg/kg did not induce any significant change in liver lipid peroxidation. Paraquat treatment resulted in a significant decrease of total glutathione concentration and increased oxidized glutathione in both lung and liver. These effects were abolished by treatment with melatonin. The results suggest that melatonin confers marked protection against paraquat-induced oxidative toxicity in both the lung and liver.

The effects of parathion on male rat pineal N-acetyltransferase (NAT) activity, hydroxyindole-O-methyltransferase (HIOMT) activity and pineal and serum melatonin levels at the end of light period (2000 h) and at night (2300 h and 0100 h) were studied. Additionally, pineal levels of 5-hydroxytryptophan (5-HTP), serotonin (5-HT), and 5-hydroxyindole acetic acid (5-HIAA) were estimated. Parathion was administered intragastrically at total doses (over 6 days) of either 6.5 or 13 mg/kg. Control rats received vehicle (corn oil) only. During the study, the rats were exposed to light:dark cycles of 14:10 with light off at 2100 h. Pineal NAT activity was increased at 0100 h following parathion administration at both doses, but HIOMT activity was unaffected. Pineal and serum melatonin levels were increased at night (2300 h and 0100 h) after the 13 mg/kg dose of parathion while the lower dose increased pineal melatonin only at 0100 h. Also, both doses decreased 5-HTP at 2000 h while the lower dose increased it at 2300; 5-HT was significantly decreased at 2300 h and 5-HIAA levels were lower but only significantly so for the 13 mg/kg dose at 2000 h. The results indicate that parathion has significant effects on pineal melatonin synthesis by mechanisms which remain unknown.

The purpose of this study was to examine the effects of chronic administration of sublethal doses of carbaryl on pineal melatonin synthesis. N-methyl 1-naphthylcarbamate (carbaryl) (8.33 mg/kg B.W. daily) was administered orally to adult male albino rats for 6 successive days. Nocturnal (0100) N-acetyltransferase and hydroxyindole-O-methyltransferase activities were increased (roughly 75% and 60%, respectively) by carbaryl administration; likewise, carbaryl augmented serum melatonin levels at 2300. Pineal tryptophan. 5-hydroxytryptophan, serotonin, and 5-hydroxindole acetic acid levels were unaffected at all three time points. The results indicate that the carbamate pesticide, i.e., carbaryl, modifies pineal melatonin synthesis in vivo.

The effects of different doses of chronically administered carbaryl on rat pineal N-acetyltransferase (NAT) activity, hydroxyindole-O-methyltransferase (HIOMT) activity and pineal and serum melatonin levels during darkness (2300 h and 0100 h) when pineal melatonin synthesis is high were studied. Additionally, pineal levels of 5-hydroxytryptophan (5-HTP), serotonin (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) were estimated. Carbaryl was administered at total doses (over 6 days) of either 50, 125 or 250 mg/kg by gastric gavage. Control rats received vehicle (corn oil) only. During the study, the rats were exposed to light/dark cycles of 14:10 with lights off at 2100 h. Pineal NAT and HIOMT activities and pineal melatonin were increased at 0100 h following carbaryl administration at all three doses. Conversely, serum melatonin was increased at 2300 h after the 250 mg/kg dose of carbaryl while all three doses of the pesticide reduced serum melatonin levels at 0100 h. Pineal 5-HTP, 5-HT and 5-HIAA levels were usually increased at 2300 h but unaffected at 0100 h. The results indicate that carbaryl has significant effects on pineal melatonin synthesis and secretion.

The effect of interferon-gamma (IFN-gamma) on melatonin production was determined in rat pineal glands in organ culture. IFN-gamma enhanced the production of melatonin in the glands incubated with either 10 nM or 1,000 nM isoproterenol (ISO, a beta-adrenergic receptor agonist) but decreased the 100 nM ISO response. The enhanced melatonin production was accompanied by either unchanged or a lower level of N-acetyltransferase (NAT) activity, whereas the suppression was accompanied by a reduced NAT activity. IFN-gamma did not change the activity of the enzyme hydroxyindole-O-methyltransferase (HIOMT) in the ISO-stimulated pineal glands. The results indicate that IFN-gamma has a dual action on the pineal gland: One is to increase melatonin production through yet unknown mechanisms, and the other is to suppress NAT activity. These results also suggest that the pineal gland, under physiological stimulation, is modulated by IFN-gamma to increase melatonin production. A hypothetical model is proposed to explain the delicate regulation of pineal function by the immune system.

The effect of organochlorine insecticides lindane (1,2,3,4,5,6-hexachlorocyclohexane) and DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane) were studied in terms of their effects on the rat pineal N-acetyltransferase (NAT) activity, hydroxyindole-O-methyltransferase (HIOMT) activity and pineal and serum melatonin levels during the day (2000h) and at night (2300 and 0100h). Additionally, pineal levels of 5-hydroxytryptophan (5-HTP), serotonin (5-HT), and 5-hydroxyindole acetic acid (5-HIAA) were estimated. Nocturnal NAT activity was increased after lindane administration; likewise, lindane augmented pineal and serum melatonin levels at 2300h. Conversely, DDT was without a statistically significant effect on either NAT activity or on pineal or serum melatonin levels. Neither lindane nor DDT significantly influenced pineal HIOMT values either during the day or at night. Likewise, neither insecticide consistently influenced pineal levels of either 5-HTP, 5-HT or 5-HIAA. The results indicate that the organochlorine insecticide, lindane, modifies pineal melatonin synthesis in vivo.