The prophylactic and anti-fibrotic activity of phthalimido-thiazole derivatives in schistosomiasis mansoni.

Schistosomiasis mansoni is considered a serious public health problem. As praziquantel is the only drug recommended by the World Health Organization for the treatment and control of schistosomiasis, the development of new drugs is of great significance. In this work, we present the antischistosomal activity of a small set of phthalimido-thiazole derivatives against Schistosoma mansoni. The effects of those derivatives on the viability of larvae juveniles and adult parasites, production and development of eggs, mortality of schistosomules in vitro by counting worms, and stages of eggs of infected animals in acute and chronic phases were evaluated, resulting in the identification of new multistage antischistosomal compounds. Additionally, a study of liver fibrogenesis was released. The phthalimido-thiazole derivatives, compounds 2b-d, 2h-j, had shown activity on schistosomules, achieving 100% mortality even at 5 mg/mL, in the first 24 h. In the chronic phase of schistosomiasis infection, compound 2i promoted a reduction in the number of immature eggs, an increase in the number of non-viable parasite eggs, a reduction in the average number of eggs in the liver and intestine, decrease in the levels of hydroxyproline in the liver, and a reduction in the areas of hepatic fibrosis. This compound also promoted an increase of IL-10 and a reduction in the level of TNF-α in the liver. Accordingly, the phthalimide-thiazole scaffold is a new starting point for the development of multistage compounds that affect S. mansoni viability, egg formation, and production.

The Prophylactic Activity of Punica granatum L. mesocarp Protects Preadipocytes against Ribosylated BSA-Induced Toxicity.

OBJECTIVE: It was aimed at comparing the glycating capacities of glucose and ribose in bovine serum albumin (BSA) and anti-glycation activity of pomegranate mesocarp extract (PME). The protective mechanism of PME against ribosylated BSA (BSARIB)-induced toxicity was also investigated. METHODS: BSA was incubated with glucose or ribose in the presence or absence of PME for 15 days. In preadipocytes pretreated with PME, cell viability, ROS production, lipid peroxidation and mitochondrial membrane potential were investigated following 1, 6, 12, 18 and 24 h exposure to BSARIB. Nuclear translocation of NFκB was assessed at 1 h and 24 h of BSARIB insult. Accumulation of oxidized proteins, activities of intrinsic antioxidant enzymes and IL-6 secretion were also determined after 24 h exposure to BSARIB. RESULTS: Ribose was a harsher glycating agent as compared to glucose and PME showed strong anti-glycation activity by suppressing (P < 0.05) the increase in levels of fluorescent AGEs, Amadori products, protein carbonyl and advanced oxidation protein products (AOPP). In preadipocytes, BSARIB potentiated pro-apoptotic activity by inhibiting the nuclear translocation of NFκB. BSARIB induced a time dependent decrease in cell viability, which was significantly suppressed (P < 0.05) by PME. The extract also significantly reduced (P < 0.05) the time dependent increase in ROS level and associated lipid peroxidation as well as loss in mitochondrial membrane potential caused by BSARIB. PME also counteracted the BSARIB-induced accumulation of oxidized proteins, decrease in intrinsic antioxidant activity and IL-6 over-secretion. CONCLUSIONS: PME showed anti-glycation activity and afforded protection against BSARIB-induced toxicity, oxidative stress and inflammation in preadipocytes.

Gelatin-derived carbon quantum dots mitigate herbicide-induced neurotoxic effects in vitro and in vivo.

The herbicide and viologen, N, N'-dimethyl-4,4'-bipyridinium dichloride (Paraquat) is known to be toxic to neuronal cells by a multifactorial process involving an elevation in the levels of reactive oxygen species (ROS), the triggering of amyloid-protein aggregation and their accumulation, collectively leading to neuronal dyshomeostasis. We demonstrate that green-chemistry-synthesized sustainable gelatin-derived carbon quantum dots (CQDs) mitigate paraquat-induced neurotoxic outcomes and resultant compromise in organismal mortality. Gelatin-derived CQDs were found to possess antioxidant properties and ameliorated ROS elevation in paraquat-insulted neuroblastoma-derived SHSY-5Y cells, protecting them from herbicide-induced cell death. These CQDs also increased lifespan in paraquat-compromised Caenorhabditis elegans and herbicide-mediated dopamine neuron ablation. Collectively, the data underscore the ability of this sustainably synthesized, environmentally friendly biocompatible nanomaterial to protect cell lines and organisms against neurotoxic outcomes. The study findings strategically position this relatively novel nanoscopic carbon quantum framework for further testing in vertebrate trials of neurotoxic insult.