No abstract

We evaluated the inhibitory effect of melatonin, a recently discovered scavenger of free radicals, on cataract formation in the newborn rat. The glutathione synthesis inhibitor, buthionine sulfoximine (BSO) (3 mmol/kg), was intraperitoneally injected into newborn rats for 3 consecutive days starting on day 2 after birth. These glutathione depleted rats develop cataracts. Melatonin (4 mg/kg) was injected intraperitoneally into half of the rats once a day beginning at day 2 after birth; the other half of the animals received solvent daily. The incidence of cataract was observed on day 16, after the eyes of the newborn animals had opened. Both reduced glutathione (GSH) and oxidized glutathione (GSSG) levels were measured. Cataracts were observed in all animals (18/18) treated with BSO plus solvent. The incidence of the cataract in the animals cotreated with melatonin was only 6.2% (1/15). Total lenticular glutathione (GSH + GSSG) levels in BSO only treated rats were reduced by 97%. The total glutathione in the lens of the BSO plus melatonin group was significantly higher (by 3%) than that of the BSO only group. The percentage of the total glutathione as GSSG for the BSO plus solvent group was higher than the control value. Cotreatment of BSO injected rats with melatonin (4 mg/kg/day) clearly reduced cataract formation proving that it is directly or indirectly protective against oxidative stress which accompanies glutathione deficiency. The inhibitory effects of melatonin on cataract formation in this study could be due to melatonin's free radical scavenging activity or due to its stimulatory effect on glutathione production.

The protective effect of melatonin on lipopolysaccharide (LPS)-induced oxidative damage in phenobarbital-treated rats was measured using the following parameters: changes in total glutathione (tGSH) concentration, levels of oxidized glutathione (GSSG), the activity of the antioxidant enzyme glutathione peroxidase (GSH-PX) in both brain and liver, and the content of cytochrome P450 reductase in liver. Melatonin was injected intraperitoneally (ip, 4mg/kg BW) every hour for 4 h after LPS administration; control animals received 4 injections of diluent. LPS was given (ip, 4 mg/kg) 6 h before the animals were killed. Prior to the LPS injection, animals were pretreated with phenobarbital (PB), a stimulator of cytochrome P450 reductase, at a dose 80 mg/kg BW ip for 3 consecutive days. One group of animals received LPS together with Nw-nitro-L-arginine methyl ester (L-NAME), a blocker of nitric oxide synthase (NOS) (for 4 days given in drinking water at a concentration of 50 mM). In liver, PB, in all groups, increased significantly both the concentration of tGSH and the activity of GSH-PX. When the animals were injected with LPS the levels of tGSH and GSSG were significantly higher compared with other groups while melatonin and L-NAME significantly enhanced tGSH when compared with that in the LPS-treated rats. Melatonin alone reduced GSSG levels and enhanced the activity of GSH-PX in LPS-treated animals. Additionally, LPS diminished the content of cytochrome P450 reductase with this effect being largely prevented by L-NAME administration. Melatonin did not change the content of P450 either in PB- or LPS-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

No abstract

The present study used male Sprague-Dawley rats to investigate changes in glutathione [reduced (GSH) and oxidized GSH (GSSG)]. lipid peroxidation (as indicated by tissue levels of malonaldehyde and 4-hydroxyalkenals), and the activity of the antioxidant enzyme glutathione peroxidase after a bout of swimming (30 min.) with or without melatonin (N-acetyl-5-methoxytryptamine) treatment. In muscle, the concentration of GSH and the GSH/GSSG ratio were decreased following 30 min. of swimming: these changes are indicative of enhanced oxidative stress. Pretreatment with melatonin prevented these effects. In liver, swimming increased significantly both GSH and GSSG, and decreased the GSH/GSSG ratio. When animals were treated with melatonin, concentrations of GSH and GSSG were also increased after swimming: however, the reduction in the GSH/GSSG ratio was prevented by melatonin. Brain GSH/GSSG ratio was not affected by exercise or by melatonin. Swimming enhanced the levels of lipid peroxidation products is muscle: this was prevented in animals treated with melatonin. Glutathione peroxidase activity was significantly elevated after swimming in both liver and brain with the change not being influenced by concurrent melatonin treatment. It is concluded that swimming imposes an oxidative stress on liver and skeletal muscle and the results show that melatonin confers partial protection against oxidative toxicity, especially in muscle.