Melatonin prevents brain oxidative stress induced by obstructive jaundice in rats

Abstract

The aim of the study was to analyze the impact of melatonin on brain oxidative stress in experimental biliary obstruction. Cholestasis was done by a double ligature and section of the extrahepatic biliary duct. Melatonin was injected intraperitoneally (500 microg/kg/day). Malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) contents were determined in the brain tissue. Biliary obstruction raised MDA and reduced GSH contents in the cortex, cerebellum, and hypothalamus areas. Moreover, the scavenger enzyme activity significantly dropped in all areas of the brain. Melatonin drastically reduced MDA concentration and enhanced GSH concentration, as well as all antioxidant enzyme activity in all brain areas obtained from the bile duct-ligated animals. In conclusion, the treatment with melatonin decreased lipid peroxidation and recovered the antioxidant status in the brain from cholestatic animals.

Quantification of Superoxide Radical in the Brain of Rats with Experimentally Induced Obstructive Jaundice

“…In keeping with the present findings, decrease in the indirect markers of low oxidative stress, reduced glutathione and protein thiols, along with increase in the indirect markers of high oxidative stress protein disulphide and lipid peroxidation suggested the existence of oxidative stress as early as 5 days after bile duct ligation [4]. These findings have also been recently confirmed by other research groups [5,6]. Direct comparison of the results between the previous studies and the present one is inappropriate, since in this study we quantified O 2 -anion that leads to oxidative stress, whereas previous studies measured the thiol and lipid oxidation products assuming to result from reactions with O 2 -s and others ROS.…”

Melatonin Ameliorates Bile Duct Ligation-Induced Systemic Oxidative Stress and Spatial Memory Deficits in Developing Rats

“…M1000 group showed lowest plasma GSH levels whereas highest liver GSH levels and GSH/GSSG ratios suggesting melatonin may regulate the hepatic efflux of GSH to prevent liver damage. In contrast to adult BDL-induced cholestatic rat, we could not find a significant difference of MDA levels or GSH/GSSG ratios in either brain cortex or hippocampus (4,6,27). Nevertheless, data from young BDL rats are scarce.…”

“…Melatonin could protect DNA molecules, proteins, and membrane lipids from the harmful effects of free radicals, via the mechanism of electron donation with the generation of indolyl cation radical, a molecule also able to scavenge the toxic superoxide radical (17,18). In the setting of experimental cholestasis, melatonin has been found to increase liver activity of catalase, superoxide dismutase, GSH peroxidase, GSH reductase and GSH transferase (24,25), increase renal activity of reduced GSH (23), increase brain activity of superoxise dismutase, catalase, and GSH peroxidase (27). Although, we could not detect either MDA or GSH/GSSG ratio differences in brain cortex or hippocampus, these results suggest melatonin's action in brain may be via other mechanisms.…”

“…Melatonin can decrease oxidative injury and was found to be protective after experimental traumatic brain injury (20), hypoxic brain damage (21), and seizure-induced lipid peroxidation (22). Moreover, melatonin can prevent cholestasis-induced renal (23), liver (24 -26), and brain damage (27). In addition, melatonin can pass blood-brain barrier and has been safe in children and is widely used in clinical conditions (28).…”

“…A fifth group rats with BDL for 2 wks and concomitant melatonin 1000 g/kg/d intraperitoneal injection was designed as melatonin (1000 g/kg/d) (M1000) group (n ϭ 10). Melatonin was administered at the dose of 500 g/kg/d according to previous studies (23,27). However, higher dose of melatonin had been used in treating rat brain disorders; hence, melatonin 1000 g/kg/d was also tested in this study (20,22).…”