Neuroprotective potential of pyrazole benzenesulfonamide derivative T1 in targeted intervention against PTZ-induced epilepsy-like condition in in vivo zebrafish model.

Epilepsy is a chronic neurological disease characterized by a persistent susceptibility to seizures. Pharmaco-resistant epilepsies, impacting around 30 % of patients, highlight the urgent need for improved treatments. Neuroinflammation, prevalent in epileptogenic brain regions, is a key player in epilepsy, prompting the search for new mechanistic therapies. Hence, in this study, we explored the anti-inflammatory potential of pyrazole benzenesulfonamide derivative (T1) against pentylenetetrazole (PTZ) induced epilepsy-like conditions in in-vivo zebrafish model. The results from the survival assay showed 79.97 ± 6.65 % at 150 µM of T1 compared to PTZ-group. The results from reactive oxygen species (ROS), apoptosis and histology analysis showed that T1 significantly reduces cellular damage due to oxidative stress in PTZ-exposed zebrafish. The gene expression analysis and neutral red assay results demonstrated a notable reduction in the inflammatory response in zebrafish pre-treated with T1. Subsequently, the open field test unveiled the anti-convulsant activity of T1, particularly at a concentration of 150 µM. Moreover, both RT-PCR and immunohistochemistry findings indicated a concentration-dependent potential of T1, which inhibited COX-2 in zebrafish exposed to PTZ. In summary, T1 protected zebrafish against PTZ-induced neuronal damage, and behavioural changes by mitigating the inflammatory response through the inhibition of COX-2.

Toxic ties: Unraveling the complex relationship between endocrine disrupting chemicals and chronic kidney disease.

Environmental pollution is inherently linked to several metabolic diseases and high mortality. The kidney is more susceptible to environmental pollutants compared to other organs as it is involved in concentrating and filtering most of these toxins. Few epidemiological studies revealed the intrinsic relationship between exposure to Endocrine Disrupting Chemicals (EDCs) and CKD development. Though EDCs have the potential to cause severe pathologies, the specific molecular mechanisms by which they accelerate the progression of CKD remain elusive. In particular, our understanding of how pollutants affect the progression of chronic kidney disease (CKD) through the gut-kidney axis is currently limited. EDCs modulate the composition and function of the gut microbial community and favor the colonization of harmful gut pathogens. This alteration leads to an overproduction of uremic toxin and membrane vesicles. These vesicles carry several inflammatory molecules that exacerbate inflammation and renal tissue damage and aggravate the progression of CKD. Several experimental studies have revealed potential pathways by which uremic toxin further aggravates CKD. These include the induction of membrane vesicle production in host cells, which can trigger inflammatory pathways and insulin resistance. Reciprocally, CKD can also modulate gut bacterial composition that might further aggravate CKD condition. Thus, EDCs pose a significant threat to kidney health and the global CKD burden. Understanding this complicated issue necessitates multidisciplinary initiatives such as strict environmental controls, public awareness, and the development of novel therapeutic strategies targeting EDCs.