The food additive E171 (titanium dioxide, TiO₂), is widely used in foods, pharmaceuticals and cosmetics. It is a fine white powder, with at least one third of its particles sized in the nanoparticulate (˂100 nm range, TiO₂ NPs). The use of E171 is controversial as its relevant risk assessment has never been satisfactorily accomplished. In vitro and in vivo studies have shown dose‐dependent toxicity in various organs including the liver. TiO₂ NPs have been shown to induce inflammation, cell death and structural and functional changes within the liver. The toxicity of TiO₂ NPs in experimental models varies between organs and according to their physiochemical characteristics and parameters such as dosage and route of administration. Among these factors, ingestion is the most significant exposure route, and the liver is a key target organ. The aim of this review is to highlight the reported adverse effects of orally administered TiO₂ NPs on the liver and to discuss the controversial state of its toxicity.

Immunocompromised hind limb ischemia (HLI) murine models are essential for preclinical evaluation of human cell-based therapy or biomaterial-based interventions. These models are used to generate proof of principle that the approach is effective and also regulatory preclinical data required for translation to the clinic. However, surgical variations in creation of HLI models reported in the literature introduce variability in the pathological manifestation of the model, in consequence affecting therapeutic endpoints. This study aims to compare the extent of vascular regeneration in HLI-induced immunocompromised murine models to obtain a stable and more reproducible injury model for testing. Athymic and Balb/C nude mice underwent HLI surgery with single and double ligation of femoral artery (FA). The recovery from surgery was observed over a period of 2 weeks with respect to ischemia reperfusion using laser Doppler and clinical signs of necrosis and ambulatory impairment. Double ligation of the FA results in a more severe response to ischemia in Balb/C with endogenous perfusion recovery up to 50% ± 10% compared with 75% ± 20% in athymic nude mice. Single iliac artery (IA) and FA lead to creation of mild ischemia compared with femoral artery–vein (FAV) pair ligation in Balb/C. Microcirculatory parameters indicate significantly lower capillary numbers (26 ± 3/mm ² ) and functional capillary density (203 ± 5 cm/cm ² ) in the FAV group. In this study, we demonstrate a reproducible, arterial double ligation in an immunocompromised Balb/C nude mouse model that exhibits characteristic pathological signs of ischemia with impaired endogenous recovery.

Titanium dioxide (TiO₂) is used extensively as a white pigment in the food industry, personal care, and a variety of products of everyday use. Although TiO₂has been categorized as a bioinert material, recent evidence has demonstrated different toxicity profiles of TiO₂nanoparticles (NPs) and a potential health risk to humans. Studies indicated that titanium dioxide enters the systemic circulation and accumulates in the lungs, liver, kidneys, spleen, heart, and central nervous system and may cause oxidative stress and tissue damage in these vital organs. Recently, some studies have raised concerns about the possible detrimental effects of TiO₂NPs on glucose homeostasis. However, the findings should be interpreted with caution due to the methodological issues. This article aims to evaluate current evidence regarding the effects of TiO₂NPs on glucose homeostasis, including possible underlying mechanisms. Furthermore, the limitations of current studies are discussed, which may provide a comprehensive understanding and new perspectives for future studies in this field.

Acute liver injury (ALI) is a highly destructive and potentially life-threatening condition, exacerbated by physical and psychological stress. The endocannabinoid system plays a key role in modulating stress and hepatic function. The aim of this study was to examine the development of acute liver injury in the genetically susceptible stress-sensitive Wistar-Kyoto (WKY) rat compared with normo-stress-sensitive Sprague Dawley (SD) rats, and associated changes in the endocannabinoid system. Administration of the hepatotoxin lipopolysaccharide/D-Galactosamine (LPS/GalN) resulted in marked liver injury in WKY, but not SD rats, with increased alanine aminotransferase (ALT), aspartate aminotransferase (AST) and glutamate dehydrogenase (GLDH) plasma levels, significant histopathological changes, increased hepatic pro-inflammatory cytokine expression and caspase-3 activity and expression and reduced Glutathione (GSH) activity. Furthermore, compared to SD controls, WKY rats display increased anandamide and 2-Arachidonoylglycerol levels concurrent with decreased expression of their metabolic enzymes and a decrease in cannabinoid (CB)₁ receptor expression following LPS/GalN. CB₁ antagonism with AM6545 or CB₂ agonism with JWH133 did not alter LPS/GalN-induced liver injury in SD or WKY rats. These findings demonstrate exacerbation of acute liver injury induced by LPS/GalN in a stress-sensitive rat strain, with effects associated with alterations in the hepatic endocannabinoid system. Further studies are required to determine if the endocannabinoid system mediates or modulates the exacerbation of liver injury in this stress-sensitive rat strain.