Exposure to bisphenol A (BPA) is unavoidable and it has far-reaching negative effects on living systems. This study aimed to explore the toxic effects of BPA in an experimental animal model through a metabolomics approach that is useful in measuring small molecule perturbations. Beside this, we also examined the ameliorative effects of resveratrol (RSV) against BPA-induced disturbances in experimental mice. This study was conducted for 28 days, and the results showed that BPA indeed induced an impairment in amino acid metabolism, taking place in the mitochondria by significantly (p < 0.05) decreasing the levels of certain amino acids, i.e., taurine, threonine, asparagine, leucine, norleucine, and glutamic acid in the mice plasma. However, the administration of RSV did prove effective against the BPA-induced intoxication and significantly (p < 0.05) restored the level of free amino acids. Lipid metabolites, L-carnitine, sphinganine, phytosphingosine, and lysophosphatidylcholine were also determined in the mice serum. A significant (p < 0.05) decline in glutathione peroxidase (GPx), superoxide dismutase (SOD,) glutathione, and catalase levels and an elevation in malondialdehyde level in the BPA group confirmed the generation of oxidative stress and lipid peroxidation in experimental mice exposed to BPA. The expression of Carnitine palmitoyltransferase I (CPT-I), carnitine palmitoyltransferase II (CPT-II), lecithin–cholesterol acyltransferase (LCAT), carnitine O-octanoyltransferase (CROT), carnitine-acylcarnitine translocase (CACT), and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) genes was significantly upregulated in the liver tissue homogenates of experimental mice exposed to BPA, although RSV regulated the expression of these genes when compared with BPA treated experimental mice. CPT-I, CPT-II, and CACT genes are located in the mitochondria and are involved in the metabolism and transportation of carnitine. Hence, this study confirms that BPA exposure induced oxidative stress, upregulated gene expression, and impaired lipid and amino acid metabolism in experimental mice.

Our study aimed to conduct a comprehensive biochemical profiling and metabolomics analysis to investigate the effects of arsenic-induced metabolic disorders, with a specific focus on disruptions in lipid metabolism, amino acid metabolism, and carbohydrate metabolism. Additionally, we sought to assess the therapeutic potential of resveratrol (RSV) as a remedy for arsenic-induced diabetes, using metformin (MF) as a standard drug for comparison. We measured the total arsenic content in mouse serum by employing inductively coupled plasma mass spectrometry (ICP-MS) after administering a 50-ppm solution of sodium arsenate (50 mg/L) in purified water. Our findings revealed a substantial increase in total arsenic content in the exposed group, with a mean value of 166.80 ± 8.52 ppb (p < 0.05). Furthermore, we investigated the impact of arsenic exposure on various biomarkers using enzyme-linked immunosorbent assay (ELISA) methods. Arsenic exposed mice exhibited significant hyperglycemia (p < 0.001) and elevated levels of homeostatic model assessment of insulin resistance (HOMA-IR), hemoglobin A1c (Hb1Ac), Inflammatory biomarkers as well as liver and kidney function biomarkers (p < 0.05). Additionally, the levels of crucial enzymes linked to carbohydrate metabolism, including α-glucosidase, hexokinase, and glucose-6-phosphatase (G6PS), and oxidative stress biomarkers, such as levels of glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), catalase, and superoxide dismutase (SOD), were significantly reduced in the arsenic-exposed group compared to the control group (p < 0.05). However, the level of MDA was significantly increased. Molecular analysis of gene expression indicated significant upregulation of key enzymes involved in lipid metabolism, such as carnitine palmitoyl-transferase-I (CPT-I), carnitine palmitoyl-transferase-II (CPT-II), lecithin–cholesterol acyltransferase (LCAT), and others. Additionally, alterations in gene expression related to glucose transporter-2 (GLUT-2), glucose-6-phosphatase (G6PC), and glucokinase (GK), associated with carbohydrate metabolism, were observed. Amino acid analysis revealed significant decreases in nine amino acids in arsenic-exposed mice. Metabolomics analysis identified disruptions in lipid metabolomes, amino acids, and arsenic metabolites, highlighting their involvement in essential metabolic pathways. Histopathological observations revealed significant changes in liver architecture, hepatocyte degeneration, and increased Kupffer cells in the livers of arsenic-exposed mice. In conclusion, these findings enhance our comprehension of the impact of environmental toxins on metabolic health and offer potential avenues for remedies against such disruptions.