Iron role paradox in nerve degeneration and regeneration.

Iron accumulates in the neural tissue during peripheral nerve degeneration. Some studies have already been suggested that iron facilitates Wallerian degeneration (WD) events such as Schwann cell de-differentiation. On the other hand, intracellular iron levels remain elevated during nerve regeneration and gradually decrease. Iron enhances Schwann cell differentiation and axonal outgrowth. Therefore, there seems to be a paradox in the role of iron during nerve degeneration and regeneration. We explain this contradiction by suggesting that the increase in intracellular iron concentration during peripheral nerve degeneration is likely to prepare neural cells for the initiation of regeneration. Changes in iron levels are the result of changes in the expression of iron homeostasis proteins. In this review, we will first discuss the changes in the iron/iron homeostasis protein levels during peripheral nerve degeneration and regeneration and then explain how iron is related to nerve regeneration. This data may help better understand the mechanisms of peripheral nerve repair and find a solution to prevent or slow the progression of peripheral neuropathies.

Thiamine as a peripheral neuro-protective agent in comparison with N-acetyl cysteine in axotomized rats.

Objectives: In this study, the impact of thiamine (Thi), N-acetyl cysteine (NAC), and dexamethasone (DEX) were investigated in axotomized rats, as a model for neural injury. Materials and Methods: Sixty-five axotomized rats were divided into two different experimental approaches, the first experiments included five study groups (n=5): intrathecal Thi (Thi.it), intraperitoneal (Thi), NAC, DEX, and control. Cell survival was assessed in L5DRG in the 4th week by histological assessment. In the second study, 40 animals were engaged to assess Bcl-2, Bax, IL-6, and TNF-α expression in L4-L5DRG in the 1st and 2nd weeks after sural nerve axotomy under treatment of these agents (n=10). Results: Ghost cells were observed in morphological assessment of L5DRG sections, and following stereological analysis, the volume and neuronal cell counts significantly were improved in the NAC and Thi.it groups in the 4th week (P<0.05). Although Bcl-2 expression did not show significant differences, Bax was reduced in the Thi group (P=0.01); and the Bcl-2/Bax ratio increased in the NAC group (1st week, P<0.01). Furthermore, the IL-6 and TNF-α expression decreased in the Thi and NAC groups, on the 1st week of treatment (P≤0.05 and P<0.01). However, in the 2nd week, the IL-6 expression in both Thi and NAC groups (P<0.01), and the TNF-α expression in the DEX group (P=0.05) were significantly decreased. Conclusion: The findings may classify Thi in the category of peripheral neuroprotective agents, in combination with routine medications. Furthermore, it had strong cell survival effects as it could interfere with the destructive effects of TNF-α by increasing Bax.

Protective effects of acetyl-L-carnitine against serum and glucose deprivation-induced apoptosis in rat adipose-derived mesenchymal stem cells.

Low survival rate of grafted mesenchymal stem cells (MSC) in injured tissue is one of the major limitations of stem cell therapy. One of the most important factors that limits the MSCs survival rate and retention is ischemic stress, which can lead to damage to all components of the cell. In particular, it can damage mitochondria, that play an important role in apoptosis with releasing apoptotic factors. Therefore, we investigated the protective effects of Acetyl-L-carnitine (ALCAR) against serum and glucose deprivation (SGD) in adipose-derived mesenchymal stem cells (AD-MSCs). We measured cell viability, proliferation, and apoptosis in cells experiencing SGD stress for 8 h with exposure to varying concentrations of ALCAR. Results showed that ALCAR protects cells against SGD stress by reducing apoptosis. Its protective effects are associated with reductions in cleaved caspase-3 and attenuation of apoptosis. Result showed that ALCAR exhibits protective effects against SGD-induced damage to AD-MSCs by enhancing the expression of survival signals and by decreasing the expression of death signals.

Effects of Neonatal Exposure to Zearalenone on Puberty Timing, Hypothalamic Nuclei of AVPV and ARC, and Reproductive Functions in Female Mice.

It is now established that mycoestrogen zearalenone (ZEN) disrupts reproductive physiology, but the specific mechanisms by which this occurs remain unknown, especially in brain. Growing evidence suggests that populations of estradiol (E2)-sensitive neurons in anteroventral periventricular (AVPV) and arcuate (ARC) nuclei, especially kisspeptin neurons, play a pivotal role in the timing of puberty onset, ovulation, and normal reproduction. The present study was conducted to find whether the ZEN can cause estrogen-like actions during the critical period of neonatal differentiation. In this study, we compared the effect of neonatal exposure to sesame oil, E2 benzoate (EB, 20 µg/kg body weight [bw]), and 3 various doses: 0.2, 1, and 2 mg/kg bw of ZEN (0.2, 1, and 2 ZEN) on the onset of puberty and estrus cyclicity as well as ovarian follicular profile, kisspeptin expression, and neuronal density in AVPV and ARC hypothalamic nuclei and E2 and luteinizing hormone (LH) levels on postnatal day 70. Control mice received no treatment. Vaginal opening was significantly advanced by EB and 2 ZEN. Disrupted estrus cycles and decreased follicular profiles were observed in EB, 1 ZEN, and 2 ZEN animals. In addition, EB, 1 ZEN, and 2 ZEN reduced the expression of kisspeptin and neuronal density of AVPV and ARC nuclei and caused a decrease in the LH and an increase in E2 plasma levels. Taken together, our observations provide physiological evidence that neonatal exposure to ZEN exerts estrogen-like actions in the estrogen-sensitive hypothalamic AVPV and ARC nuclei, controlling reproductive functions in adult female mice.

Oestrogenic action of neonatal tamoxifen on the hypothalamus and reproductive system in female mice.

Tamoxifen, a selective oestrogen receptor modulator, is widely used for both the treatment and prevention of breast cancer in women; however, it is known to have adverse effects in the female reproductive system. Growing evidence suggests that oestrogen-sensitive neuron populations of the anteroventral periventricular (AVPV) nucleus and arcuate (ARC) nucleus, especially kisspeptin neurons, play a pivotal role in the timing of puberty onset and reproductive function. The aim of the present study was to evaluate whether neonatal exposure to tamoxifen affects oestrogenic actions in the brain and reproductive function in mice. On 1 to 5 postnatal days, female pups were injected subcutaneously with sesame oil (sham), oestradiol benzoate (EB; 20 µg kg-1), tamoxifen (0.4 mg kg-1) or EB+tamoxifen. Control mice received no treatment. Mice in the EB, tamoxifen and tamoxifen+EB groups exhibited advanced vaginal opening, disrupted oestrous cycles and a decreased follicular pool. Conversely, in these groups, there was a reduction in kisspeptin (Kiss1) mRNA expression, the neuronal density of AVPV and ARC nuclei and LH and oestradiol concentrations in the serum. The results of the present study confirm oestrogenic actions of tamoxifen in the brain and reproductive system. In addition, we show, for the first time, that tamoxifen has oestrogenic effects on the oestrogen-sensitive hypothalamic AVPV and ARC nuclei controlling the reproductive axis in female mice.

Feselol enhances the cytotoxicity and DNA damage induced by cisplatin in 5637 cells.

Transitional cell carcinoma (TCC), which is the most common type of bladder cancer, shows resistance to chemotherapeutic agents due to the overexpression of drug efflux pumps. In this study, the effects of feselol, a sesquiterpene coumarin extracted from Ferula badrakema, on cisplatin cytotoxicity were investigated in 5637 cells, a TCC subline. Cell viability and DNA lesion were evaluated by thiazolyl blue tetrazolium bromide and comet assays, respectively. Feselol had no significant cytotoxic effect in 5637 cells but at 32 microg/mL it increased the cytotoxicity of 1 microg/mL cisplatin by 37% after 24 h. Furthermore, the comet assay revealed that DNA damage induced by cisplatin in 5637 cells is enhanced by 31% when used in combination with feselol. Therefore, feselol might be considered as an effective reversal agent for future in vivo and clinical studies.