Gallic acid is one of the most important polyphenolic compounds, which is considered an excellent free radical scavenger. 6-Hydroxydopamine (6-OHDA) is a neurotoxin, which has been implicated in mainly Parkinson's disease (PD). In this study, we investigated the molecular mechanism of the neuroprotective effects of gallic acid on 6-OHDA induced apoptosis in human dopaminergic cells, SH-SY5Y. Our results showed that 6-OHDA induced cytotoxicity in SH-SY5Y cells was suppressed by pre-treatment with gallic acid. The percentage of live cells (90%) was high in the pre-treatment of gallic acid when compared with 6-OHDA alone treated cell line. Moreover, gallic acid was very effective in attenuating the disruption of mitochondrial membrane potential, elevated levels of intracellular ROS and apoptotic cell death induced by 6-OHDA. Gallic acid also lowered the ratio of the pro-apoptotic Bax protein and the anti-apoptotic Bcl-2 protein in SH-SY5Y cells. 6-OHDA exposure was up-regulated caspase-3 and Keap-1 and, down-regulated Nrf2, BDNF and p-CREB, which were sufficiently reverted by gallic acid pre-treatment. These findings indicate that gallic acid is able to protect the neuronal cells against 6-OHDA induced injury and proved that gallic acid might potentially serve as an agent for prevention of several human neurodegenerative diseases caused by oxidative stress and apoptosis.
Mature Merino rams were made hypothyroid by daily oral drenching with methylthiouracil or hyperthyroid by daily subcutaneous injections of thyroxine for 8 weeks. Neither hypothyroidism nor hyperthyroidism had any apparent effect on either spermatogenesis or daily sperm production, but motility of ejaculated spermatozoa and circulating testosterone concentrations were reduced in both conditions. The ratio of testosterone concentrations in plasma from the internal spermatic vein to those in peripheral blood plasma was higher in hyperthyroid (21.2 +/- 3.5) than in control (11.1 +/- 4.4) and hypothyroid (7.6 +/- 1.4) rams. The basal secretion rate for testosterone was slightly lower in hypothyroid rams and testosterone responses to human chorionic gonadotrophin and after LH-releasing hormone (LHRH) were very much reduced. Basal serum LH levels were low in both hypothyroid and hyperthyroid rams compared with controls whereas there were no differences in FSH levels. The LH response to exogenous LHRH was reduced in hypothyroid rams but not in hyperthyroid rams. Serum prolactin levels on the other hand were higher than control in both hypothyroid and hyperthyroid rams. Reduced testosterone secretion in hypothyroid rams indicates that the normal function of Leydig cells depends on an adequate level of thyroid hormones. The decrease in circulating testosterone concentrations in hyperthyroid rams with normal secretion rates suggests an increased testosterone clearance rate in these animals. The decreased spermatozoal motility in hypo- and hyperthyroid rams suggests that the lowered testosterone level in these animals has altered the androgen-dependent maturation of spermatozoa in the epididymis.(ABSTRACT TRUNCATED AT 250 WORDS)
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