Pelvic irradiation induces behavioural and neuronal damage through gut dysbiosis in a rat model.

Radiation exposure can cause gut dysbiosis and there is a positive correlation between gut microbial imbalance and radiation-induced side effects in cancer patients. However, the influence of radiation on the gut-brain axis (GBA) and its neurological consequences are not well understood. Therefore, this study aimed to investigate the impact of pelvic irradiation on gut microbiota and the brain. Sprague Dawley rats were irradiated with a single dose of 6 Gy, and faecal samples were collected at different time points (7 and 12-days post-irradiation) for microbial analysis. Behavioural, histological, and gene expression analysis were performed to assess the effect of microbial dysbiosis on the brain. The findings indicated alterations in microbial diversity, disrupted intestinal morphology and integrity, neuronal death-related brain changes, neuroinflammation and reduced locomotor activity. Hippocampal gene expression analysis also showed a reduced expression of neural plasticity-related genes. Overall, this study demonstrated that pelvic irradiation affects gut microbiota, intestinal morphology, integrity, brain neuronal maturation, neural plasticity gene expression, and behaviour.

Organophosphate pesticide-induced toxicity through DNA damage and DNA repair mechanisms.

Organophosphate pesticides (OPs) are widely used in agriculture, healthcare, and other industries due to their ability to kill pests. However, OPs can also have genotoxic effects on humans who are exposed to them. This review summarizes the research on DNA damage caused by OPs, the mechanisms behind this damage, and the resulting cellular effects. Even at low doses, OPs have been shown to damage DNA and cause cellular dysfunction. Common phenomena seen in cells that are exposed to OPs include the formation of DNA adducts and lesions, single-strand and double-strand DNA breaks, and DNA and protein inter and intra-cross-links. The present review will aid in comprehending the extent of genetic damage and the impact on DNA repair pathways caused by acute or chronic exposure to OPs. Additionally, understanding the mechanisms of the effects of OPs will aid in correlating them with various diseases, including cancer, Alzheimer's, and Parkinson's disease. Overall, knowledge of the potential adverse effects of different OPs will help in monitoring the health complications they may cause.

Pesticides Exposure-Induced Changes in Brain Metabolome: Implications in the Pathogenesis of Neurodegenerative Disorders.

Pesticides have been used in agriculture, public health programs, and pharmaceuticals for many decades. Though pesticides primarily target pests by affecting their nervous system and causing other lethal effects, these chemical entities also exert toxic effects in inadvertently exposed humans through inhalation or ingestion. Mounting pieces of evidence from cellular, animal, and clinical studies indicate that pesticide-exposed models display metabolite alterations of pathways involved in neurodegenerative diseases. Hence, identifying common key metabolites/metabolic pathways between pesticide-induced metabolic reprogramming and neurodegenerative diseases is necessary to understand the etiology of pesticides in the rise of neurodegenerative disorders. The present review provides an overview of specific metabolic pathways, including tryptophan metabolism, glutathione metabolism, dopamine metabolism, energy metabolism, mitochondrial dysfunction, fatty acids, and lipid metabolism that are specifically altered in response to pesticides. Furthermore, we discuss how these metabolite alterations are linked to the pathogenesis of neurodegenerative diseases and to identify novel biomarkers for targeted therapeutic approaches.

Effects of low dose ionizing radiation on the brain- a functional, cellular, and molecular perspective.

Over the years, the advancement of radio diagnostic imaging tools and techniques has radically improved the diagnosis of different pathophysiological conditions, accompanied by increased exposure to low-dose ionizing radiation. Though the consequences of high dose radiation exposure on humans are very well comprehended, the more publicly relevant effects of low dose radiation (LDR) (≤100 mGy) exposure on the biological system remain ambiguous. The central nervous system, predominantly the developing brain with more neuronal precursor cells, is exceptionally radiosensitive and thus more liable to neurological insult even at low doses, as shown through several rodent studies. Further molecular studies have unraveled the various inflammatory and signaling mechanisms involved in cellular damage and repair that drive these physiological alterations that lead to functional alterations. Interestingly, few studies also claim that LDR exerts therapeutic effects on the brain by initiating an adaptive response. The present review summarizes the current understanding of the effects of low dose radiation at functional, cellular, and molecular levels and the various risks and benefits associated with it based on the evidence available from in vitro, in vivo, and clinical studies. Although the consensus indicates minimum consequences, the overall evidence suggests that LDR can bring about considerable neurological effects in the exposed individual, and hence a re-evaluation of the LDR usage levels and frequency of exposure is required.

Bi-Directional interactions between microbiota and ionizing radiation in head and neck and pelvic radiotherapy - clinical relevance.

Purpose: Rapid developments in high throughput screening technology for the detection and identification of the human microbiota have helped in understanding its influence on human health and disease. In the recent past, several seminal studies have demonstrated the influence of microbiota on outcomes of therapy-associated radiation exposure. In this review, we highlight the concepts related to the mechanisms by which radiation alters the microbiota composition linked with radiation-associated toxicity in head and neck and pelvic regions. We further discuss specific microbial changes that can be employed as a biomarker for radiation and tumor response.Conclusion: Knowledge of the influence of microbiota in radiation response and advances in microbiota manipulation techniques would help to design personalized treatment augmenting the efficacy of radiotherapy.