Differential alteration by thalidomide of the glutathione content of rat vs. rabbit conceptuses in vitro

Thalidomide has been shown to cause limb reduction defects in rabbits with much greater potency than in rats, possibly due to inherent biochemical differences between the two species. Whole embryo culture was used to make direct comparisons between thalidomide-sensitive New Zealand White rabbits and thalidomide-resistant Sprague-Dawley rats, focusing on the possible roles of glutathione (GSH) and cysteine in mechanisms of thalidomide teratogenicity. Conceptuses were treated by adding thalidomide (0, 5, 15, and 30 μM) directly to the culture media containing conceptuses of similar gestational stages. Embryos and visceral yolk sacs (VYS) were measured for changes in GSH and cysteine content using HPLC after 24 h of exposure in vitro. Thalidomide-induced (15 and 30 μM) depletion of VYS GSH occurred only in the rabbit, where GSH concentrations (pmol/μg protein) fell significantly to about 50% of control. Rat VYS did not show a significant GSH depletion at any thalidomide concentration tested. Comparison between species showed that the control rabbit VYS contained 35% less GSH than the control rat VYS. Control rat embryos and control rabbit embryos contained similar concentrations of GSH, but thalidomide treatment preferentially depleted GSH in the rabbit at lower thalidomide concentrations (5 μM). Cysteine concentrations were not significantly altered from control in the embryo or VYS of either species when treated with thalidomide. However, although control cysteine concentrations did not differ significantly between rat and rabbit VYS, control cysteine levels in rabbit embryos were 65% lower than those in control rat embryos. Rabbit conceptuses displayed lower species-specific GSH and cysteine levels and a greater propensity for thalidomide-induced GSH depletion than in rat conceptuses, consistent with the greater sensitivity of the rabbit to thalidomide teratogenicity. These thalidomide-induced and inherent species differences implicate a possible role for GSH and redox status in the mechanisms of thalidomide teratogenicity.     

The effect of lovastatin on oxidative stress and antioxidant enzymes in hydrogen peroxide intoxicated rat

Oxidative stress has been linked to the development of many diseases and hastens the progression of cardiovascular diseases. Since lovastatin is used worldwide as a cholesterol lowering drug, the present study was undertaken to evaluate the antioxidant property of lovastatin against H₂O₂ induced oxidative stress in rats. Four study groups of rats of four animals each were treated with DMSO (control), H₂O₂ (OS), lovastatin (L) and H₂O₂ + lovastatin (OSL). On the 15th day the animals were sacrificed, and the liver and heart tissues were analyzed for oxidative stress biomarkers and anti-oxidant enzymes. Results of the OSL-group showed a reduction in thiobarbituric acid reactive substances in liver (42.7%) and heart tissue (8%) compared with the control group. An increase was observed in the activity of the antioxidant enzymes, catalase (34.6% in liver and 33.3% in heart) and glutathione peroxidase (50.5% in liver and 34.7% in heart). A commensurate increase in the activity of G6PDH was observed indicating an enhanced requirement of NADPH. The ratio GSH:GSSG in liver (1.05) and heart (0.84) was satisfactorily regulated compared to the control group (1.01 in liver and 0.93 in heart). These results suggest that lovastatin possesses antioxidant activity and reduces oxidative stress.     

Effect of diallyl disulfide on the hepatic glutathione s-transferase activity in rat: Diallyl disulfide effect on the glutathione S-transferase

Glutathione s-transferase is thought to play a key role in initiating the detoxication of potential alkylating agents, including pharmacologically active compounds. It is widely accepted that garlic contains allin which is converted to allicin by alliinase. Allicin is easily degraded to diallyl disulfide and other components. This report attempted to observe the effect of diallyl disulfide on some biological activities. It was observed that the activity of serum transaminase was not changed by the treatment of diallyl disulfide. The liver cytosolic glutathione s-transferase was significantly increased. whereas the microsomal glutathione s-transferase was not increased.