Suchergebnisse

Long recognized as a normal component of organogenesis during development, apoptosis (programmed cell death) has recently been implicated in alterations of cell growth and differentiation. Tissue homeostasis is normally maintained by a balance between cell division and cell death, with apoptosis often functioning in complement to cell growth. Thus, antithetical parallels in chemical carcinogenesis can be drawn between apoptosis and the proliferative events more commonly addressed. While enhanced cell replication may contribute to an increased frequency of mutation, apoptosis within a tissue may counteract chemical carcinogenesis through loss of mutated cells. Many strong carcinogens act as tumor promoters, selectively expanding an initiated cell population advantageously over surrounding cells. Similarly, chemicals with a selective inhibition of apoptosis within an initiated population would offer a growth advantage. In contrast, chemicals causing selective apoptosis of initiated cells would be expected to have an anticarcinogenic effect. Selective apoptosis, in concert with cell‐specific replication, may explain the unique promoting effects of different carcinogens such as the peroxisome‐proliferating chemicals, phenobarbital, and 2,3,7,8‐tetrachloro‐dibenzo‐p‐dioxin (TCDD). Cell turnover, both cell growth and cell death, is central to the process of chemically induced carcinogenesis in animals and understanding its impact is a critical determinant of the relevance of chemically induced effects to man.

Following distal nerve injury significant sensory neuronal cell death occurs in the dorsal root ganglia, while after a more proximal injury, such as brachial plexus injury, a sizeable proportion of spinal motoneurons also undergo cell death. This phenomenon has been undervalued for a long time, but it has a significant role in the lack of functional recuperation, as neuronal cells cannot divide and be replaced, hence the resulting nerve regeneration is usually suboptimal. It is now accepted that this cell death is due to apoptosis, as indicated by analysis of specific genes involved in the apoptotic signalling cascade. Immediate nerve repair, either by direct suturing or nerve grafting, gives a degree of neuroprotection, but this approach does not fully prevent neuronal cell death and importantly it is not always possible. Our work has shown that pharmacological intervention using either acetyl-L-carnitine (ALCAR) or N-acetyl-cysteine (NAC) give complete neuroprotection in different types of peripheral nerve injury. Both compounds are clinically safe and experimental work has defined the best dose, timing after injury and duration of administration. The efficacy of neuroprotection of ALCAR and NAC can be monitored non-invasively using MRI, as demonstrated experimentally and more recently by clinical studies of the volume of dorsal root ganglia. Translation to patients of this pharmacological intervention requires further work, but the available results indicate that this approach will help to secure a better functional outcome following peripheral nerve injury and repair.

Puberty, governed by the endocrine system, marks the onset of reproductive functions in animals and humans through a series of physiological and biological transformations. Although the mycotoxin DON can disrupt hormonal balance and cause reproductive abnormalities, its impact on puberty-associated reproductive changes remains understudied. Considering the increased exposure of children and adolescents to DON, our study aimed to elucidate its influence on follicular integrity and the expression of pro-apoptotic proteins (BAX and Caspase-3) and anti-apoptotic protein (BCL-2) in juvenile rat ovarian tissue. We divided ten 28-day-old prepubertal Wistar rats into two dietary groups for 28 days: a control group with a mycotoxin-free diet and a DON group with a diet containing 10 mg DON/Kg. After the experiment, ovaries and uterus weights were recorded, and the ovaries underwent morphometric and immunohistochemical analysis. DON exposure led to significant reductions in both ovarian and uterine weights. Although DON intake did not change the number of ovarian follicles across developmental stages, we observed an increased expression of BAX and Caspase-3 and a decreased BCL-2 expression in most follicular stages and corpora lutea. In summary, DON exposure during puberty can interfere with apoptotic processes in diverse ovarian cell populations during early adulthood.