Dipak K. Sahoo

Protective effects of vitamin E and curcumin on l-thyroxine-induced rat testicular oxidative stress

Present study examines effects of curcumin and vitamin E on oxidative stress parameters, antioxidant defence enzymes and oxidized (GSSG) and reduced glutathione (GSH) levels in testis of L-thyroxine (T4)-induced hyperthyroid rats. The oxidative stress in T4-treated rat testis was evident from elevation in oxidative stress parameters such as lipid peroxide and protein carbonyl contents, decrease in superoxide dismutase (SOD) and catalase (CAT) activities and increase in glutathione peroxidase (GPx) activity. This is accompanied with decrease in number and mortality of epididymal sperms. When the T4-treated rats were fed with vitamin E and/or curcumin, the lipid peroxide and protein carbonyl contents in crude homogenates of testes decreased to normal level. Treatment of curcumin and/or vitamin E to T4-treated rats resulted in elevation of SOD level in postmitochondrial fraction (PMF) and mitochondrial fraction (MF) and CAT in PMF, with decreased GPx activity in MF. However, curcumin or vitamin E was unable to change GPx activity alone but in together they elevated the GPx in PMF of T4-treated rat testis. Both the antioxidants are incapable of producing significant changes in GSH:GSSG ratio of PMF of T4-treated rats. In MF, GSH:GSSG ratio elevated and decreased respectively by curcumin and vitamin E treatments to T4-treated rats, however, in together these antioxidants caused an elevated GSH:GSSG ratio with a value less than when vitamin E given alone to T4-treated rats. Vitamin E not the curcumin elevates total sperm count and percentage of live sperm impaired by hyperthyroid state. In summary, both vitamin E and curcumin are efficient in protecting testis from oxidative stress generated by T4 mainly in restoring antioxidant enzymes to the level of euthyroid animals up to some extent but vitamin E is more efficient than curcumin.

Thiol redox status critically influences mitochondrial response to thyroid hormone‐induced hepatic oxidative injury: A temporal analysis

Liver is a major target organ for thyroid hormone. The objective of the present study was to investigate temporal regulation of mitochondrial glutathione and protein‐bound thiol redox status in hyperthyroid liver. Mitochondria were isolated from control and hyperthyroid rat liver tissues at different time intervals, i.e., 24, 72, and 120 h following treatment, and sub‐fractionated into sub‐mitochondrial particles (SMPs) and matrix fractions. Increased prooxidant levels were indicative of oxidative stress in hyperthyroid mitochondria. Sensitivity to membrane lipid peroxidation (LPx) was maximal after 24 h, which subsided with time. Oxidative damage to proteins was evident as high carbonylation after 72 h; thiol residue damage was an early phenomenon. Reduced and oxidized glutathione (GSH and GSSG) pools of mitochondria were progressively depleted, thereby, impairing matrix antioxidant capacity. However, adaptations to withstand oxidative challenge were elicited in both SMPs and matrix fractions over the long term. It is concluded that maintenance of appropriate intra‐mitochondrial glutathione and protein‐bound thiol redox status could be instrumental in attenuating thyroid hormone‐induced oxidative stress. Copyright

Rat testicular mitochondrial antioxidant defence system and its modulation by aging

Accumulation of oxidative damage caused by reactive oxygen species (ROS) underlies fundamental changes found during aging. In the present study, age related effect on testicular mitochondrial oxidant generation and antioxidant defence profile was investigated in Wistar rats at 3 months (young adults), 12 months (old adults) and 24 months (senescent animals) of age. Mitochondrial oxidative stress parameters viz., lipid peroxidation (LPx), protein carbonylation, hydrogen peroxide (H2O2) generation and activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), levels of total, oxidized (GSSG) and reduced glutathione (GSH) were studied to find out their roles in maintenance of mitochondrial glutathione redox pool as a function of age. Increased levels of LPx, H2O2 and decreased GSH content accompanied by a decline in activities of SOD, GPx and GR with advancing age suggest that antioxidant defense profile of testicular mitochondria exhibit age related alterations which might play a critical role in regulating physiological functions of the testis such as steroidogenesis and spermatogenesis.

Compromised Rat Testicular Antioxidant Defence System by Hypothyroidism before Puberty

Altered thyroid function during early stages of development is known to affect adversely testicular growth, physiology, and antioxidant defence status at adulthood. The objective of the present study is to investigate the modulation of antioxidant defence status in neonatal persistent hypothyroid rats before their sexual maturation and also to identify the specific testicular cell populations vulnerable to degeneration during neonatal hypothyroidism in immature rats. Hypothyroidism was induced in neonates by feeding the lactating mother with 0.05% 6-n-propyl-2-thiouracil (PTU) through the drinking water. From the day of parturition till weaning (25 day postpartum), the pups received PTU through mothers milk (or) drinking water and then directly from drinking water containing PTU for the remaining period of experimentation. On the 31st day postpartum, the animals were sacrificed for the study. An altered antioxidant defence system marked by elevated SOD, CAT, and GR activities, with decreased GPx and GST activities were observed along with increased protein carbonylation, disturbed redox status in hypothyroid immature rat testis. This compromised testicular antioxidant status might have contributed to poor growth and development by affecting the spermatogenesis and steroidogenesis in rats before puberty as indicated by reduced germ cell number, complete absence of round spermatids, decreased seminiferous tubule diameter, and decreased testosterone level.