Recent research has helped clarify the role of cadmium (Cd) in various pathological states. We have demonstrated Cd involvement in pancreatic cancer, as well as the bioaccumulation of Cd in the pancreas. Bioaccumulation and increased toxicity suggest that Cd may also be involved in other pancreas-mediated diseases, like diabetes. Cd falls into the category of “hyperglycemic” metals, i.e., metals that increase blood glucose levels, which could be due to increased gluconeogenesis, damage to β-cells leading to reduced insulin production, or insulin resistance at target tissue resulting in a lack of glucose uptake. This review addresses the current evidence for the role of Cd, leading to insulin resistance from human, animal, and in vitro studies. Available data have shown that Cd may affect normal insulin function through multiple pathways. There is evidence that Cd exposure results in the perturbation of the enzymes and modulatory proteins involved in insulin signal transduction at the target tissue and mutations of the insulin receptor. Cd, through well-described mechanisms of oxidative stress, inflammation, and mitochondrial damage, may also alter insulin production in β-cells. More work is necessary to elucidate the mechanisms associated with Cd-mediated insulin resistance.

Phthalates and bisphenol A, classified as endocrine disruptors, have weak estrogenic, anti-androgenic properties, and affect thyroid hormone regulation. The aim of this study on male rats was to compare the subacute toxic effects of low doses of single compounds (bis (2 –ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and bisphenol A (BPA)) with the effects of their mixture through different biochemical, hormonal, and hematological parameters. Rats were divided into five experimental groups: Control (corn oil), DEHP (50 mg/kg b.w./day), DBP (50 mg/kg b.w./day), BPA (25 mg/kg b.w./day), and MIX (50 mg/kg b.w./day DEHP + 50 mg/kg b.w/day DBP + 25 mg/kg b.w./day BPA). Animals were sacrificed after 28 days of oral treatment and blood was collected for further analysis. The results demonstrated that the mixture produced significant changes in lipid profile, liver-related biochemical parameters, and glucose level. Furthermore, the opposite effects of single substances on the thyroxine level have been shown in comparison with the mixture, as well as a more pronounced effect of the mixture on testosterone level. This study contributes to the body of knowledge on the toxicology of mixtures and gives one more evidence of the paramount importance of mixture toxicity studies, especially in assessing the endocrine disruptive effects of chemicals.

Sulforaphane (SFN), which is a hydrolysis product from glucoraphanin, a compound found in cruciferous vegetables, has been studied for its potential health benefits, particularly in disease prevention and treatment. SFN has proven to be effective in combating different types of cancer by inhibiting the proliferation of tumors and triggering apoptosis. This dual action has been demonstrated to result in a reduction in tumor size and an enhancement of survival rates in animal models. SFN has also shown antidiabetic and anti-obesity effects, improving glucose tolerance and reducing fat accumulation. SFN’s ability to activate Nrf2, a transcription factor regulating oxidative stress and inflammation in cells, is a primary mechanism behind its anticancerogenic and antidiabetic effects. Its antioxidant, anti-inflammatory, and anti-apoptotic properties are also suggested to provide beneficial effects against neurodegenerative diseases. The potential health benefits of SFN have led to increased interest in its use as a dietary supplement or adjunct to chemotherapy, but there are insufficient data on its efficacy and optimal doses, as well as its safety. This review aims to present and discuss SFN’s potential in treating various diseases, such as cancer, diabetes, cardiovascular diseases, obesity, and neurodegenerative diseases, focusing on its mechanisms of action. It also summarizes studies on the pharmacological and toxicological potential of SFN in in vitro and animal models and explores its protective role against toxic compounds through in vitro and animal studies.