An autoradiographic study of cellular proliferaton, DNA synthesis and cell cycle variability in the rat liver caused by phenobarbital-induced oxidative stress: The protective role of melatonin

Abstract

Abstract:The protective effect of melatonin against phenobarbital-induced oxidative stress in the rat liver was measured based on lipid peroxidation levels (malondialedyde and 4-hydroxyalkenals). Cellular proliferation, DNA synthesis and cell cycle duration were quantitated by the incorporation of 3 H-thymidine, detected by autoradiography, into newly synthesized DNA. Two experiments were carried out in this study, each on four equal-sized groups of male rats (control, melatonin [10 mg/kg], phenobabital [20 mg/kg] and phenobarbital plus melatonin). Experiment I was designed to study the proliferative activity and rate of DNA synthesis, and measure the levels of lipid peroxidation, while experiment II was for cell cycle time determination. Relative to the controls, the phenobarbital-treated rats showed a significant increase (P < 0.01) in the lipid peroxidation levels (30.7%), labelling index (69.4%) and rate of DNA synthesis (37.8%), and a decrease in the cell cycle time. Administering melatonin to the phenobarbital-treated rats significantly reduced (P < 0.01) the lipid peroxidation levels (23.5%), labelling index (38.2%) and rate of DNA synthesis (29.0%), and increased the cell cycle time. These results seem to indicate that the stimulatory effect of phenobarbital on the oxidized lipids, proliferative activity, kinetics of DNA synthesis and cell cycle time alteration in the liver may be one of the mechanisms by which the non-genotoxic mitogen induces its carcinogenic action. Furthermore, melatonin displayed powerful protection against the toxic effect of phenobarbital.

Effect of chronic nicotine administration on the rat lung and liver: Beneficial role of melatonin

“…3C). In our previous studies (El-Sokkary, 2007;ElSokkary et al, 1999a,b) the administration of melatonin only did not change the basal levels of the parameters evaluated in this study. So we did not repeat this group again.…”

Melatonin and vitamin C administration ameliorate diazepam‐induced oxidative stress and cell proliferation in the liver of rats

“…2005). Various studies have supported the value of exogenous administration of melatonin in oxidative damage (El‐Sokkary 2000, 2 002, 2 007; Karasek et al . 2002).…”

“…1991; El‐Sokkary et al . 2003; El‐Sokkary 2007). At least one of the mechanisms implicated in the antiproliferative effect of melatonin is its action as an antioxidant, because it prevents decrease in mRNA of antioxidant enzymes induced by diazepam.…”

“…It was also found that melatonin exerts a more inhibitory effect for LPO and less stimulation for SOD and GSH, than vitamin C. It has been suggested that melatonin was one of the first biological signals to appear, in an evolutionary context (Claustrat et al 2005). Various studies have supported the value of exogenous administration of melatonin in oxidative damage (El-Sokkary 2000, 2002, 2007Karasek et al 2002).…”

“…Furthermore, these results indicate that melatonin presented a more inhibitory effect on previous parameters than vitamin C. It was found that melatonin inhibited cell proliferation in several tumour types (Hill & Blask 1988) and in several other systems (Blask 1993;El-Sokkary 2002). Melatonin is also an inhibitor of cell cycle progression, thereby increasing the number of cells in G 1 phase and reducing the percentage of cells in S phase (Cos et al 1991;El-Sokkary et al 2003;El-Sokkary 2007). At least one of the mechanisms implicated in the antiproliferative effect of melatonin is its action as an antioxidant, because it prevents decrease in mRNA of antioxidant enzymes induced by diazepam.…”