Protective effects of 17-ß-oestradiol and phytoestrogen on age-induced oxidative stress and inhibition of surfactant synthesis in rat type II pneumocytes.

Epidemiological data suggest protective effects of oestrogen and phytoestrogen on lung tissue. This study aimed to elucidate the role of 17-ß-oestradiol and phytoestrogen in age-related inhibition of surfactant synthesis and oxidative stress in rat type II pneumocytes. Forty male and 66 female Wistar rats were used. Female rats were randomly kept intact or ovariectomized at age 12 months. At age 22 months, ovariectomized rats received 17-ß-oestradiol, soy extract, or no treatment. Oxidative stress markers CO, NO, cGMP and lipid peroxide (LPO), antioxidant enzymes and phosphatidylcholine (PC) were measured in cultured type II pneumocytes isolated at ages 2, 14, 18, 22 and 24 months. Old, male and ovariectomized rats showed significantly higher CO, NO, cGMP and LPO and lower PC content and antioxidant enzymes. 17-ß-oestradiol and phytoestrogen significantly reversed these effects. In conclusion, aging and oestrogen deprivation decreased PC synthesis and altered the redox status in type II pneumocytes, which were partially restored by 17-ß-oestradiol or soy supplementation.

Melatonin, and to a lesser extent growth hormone, restores colonic smooth muscle physiology in old rats.

There is increasing evidence that aging is associated with oxidative damage, inflammation, and apoptosis in different cell types. However, there is limited information regarding aging mechanisms in colon smooth muscle. Old male Wistar rats (22 months) were treated for 10 wks with melatonin or growth hormone (GH). Animals were sacrificed at 24 months of age by decapitation. The colon was dissected and the smooth muscle homogenized. H(2)O(2) and malonyl dialdehyde (MDA) content and catalase and glutathione peroxidase (GPX) activities were determined using colorimetric kits. Expression of nuclear factor kappa B (NF-κB), cyclooxygenase 2 (COX-2), caspase-3, and caspase-9 were determined by Western blot. Aging of colon smooth muscle correlated with an increase in H(2)O(2) and MDA levels when compared with young animals in both proximal and distal segments; these changes were associated with a decrease in the catalase activity in the distal colon. Oxidative stress correlated with an increase in COX-2 and NF-κB expression, which were accompanied by an enhanced expression of the pro-apoptotic enzyme caspase-3 and its upstream enzyme, caspase-9. Melatonin treatment normalized the oxidative, inflammatory, and apoptotic patterns, whereas GH replacement, although effective in reducing oxidative stress in distal colon, did not reverse the age-related inflammation or apoptosis. These results suggest that melatonin should be the treatment of choice to most effectively recover physiological functions in aged colonic smooth muscle.