The hepatotoxicity mechanism of cantharidin (CTD), a major active component of Mylabris was explored based on liver lipidome alterations and spatial distributions in female and male rats using lipidomics and matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). After oral CTD exposure, the livers of female rats were screened for 104 differential lipids including lysophosphatidylethanolamine(LysoPE)(20:2/0:0) and diacylglycerol(DG)(18:2/22:4), whereas the livers of male rats were screened for 76 differential lipids including fatty acid(FA)(24:6) and DG(18:0/22:4). According to the MALDI-MSI results, female rats exhibited 12 differential lipids with alteration in the abundance and spatial distribution of phosphatylcholine(PC), phosphatidylethanolamine(PE), lysophosphatidylcholine(LysoPC), and LysoPE in the liver lesion area. On the other hand, male rats exhibited 8 differential lipids with changes in the abundance and spatial distribution of PC, PE, and FA in the liver lesion area. The lipidomics- and MALDI-MSI-detected differential lipids strongly disrupted glycerophospholipid metabolism in both female and male rats. Additionally, phosphatidate phosphatase (Lipin1), choline/ethanolamine phosphotransferase 1 (CEPT1), and phosphatidylethanolamine N-methyltransferase (PEMT) were screened to distinguish CTD hepatoxicity in female and male rats. Western blotting analysis demonstrated a significant elevation in Lipin1 expression in female and male rat livers, accompanied by a decrease in PEMT expression. Furthermore, CEPT1 expression increased significantly in female rat livers and decreased significantly in male rat livers. These findings suggested that CTD could disrupt lipid metabolism in a gender-specific manner. Moreover, the combination of lipidomics and MALDI-MSI could offer valuable insights into CTD-induced hepatotoxicity in rats.
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http://dx.doi.org/10.1016/j.cbi.2024.111314 | DOI Listing |
J Appl Toxicol
December 2024
School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, China.
Dihydroartemisinin (DHA) is an effective antimalarial drug with potential antitumor efficacy, yet toxicological information is limited. The present study was designed to evaluate the potential toxicity of oral DHA. DHA was administered orally by gavage to SD rats at doses of 0, 25, 50, and 75/60 mg/kg b.
View Article and Find Full Text PDFExp Neurol
December 2024
Department of Neurosurgery, University of Cincinnati, Cincinnati, OH 45267, USA; Department of Neurology and Rehabilitation Medicine, University of Cincinnati, Cincinnati, OH 45267, USA. Electronic address:
Cortical spreading depolarizations (CSDs) are the most common electrophysiological dysfunction following a traumatic brain injury (TBI), and clustered CSDs (≥3 CSDs in 2 h) are associated with poor outcomes 6 months after TBI. While many experimental studies have investigated a single CSD after injury, no known studies have investigated how time after injury affects the characteristics and impact of a CSD cluster. This study sought to determine the characteristics of a cluster of repetitive CSDs when induced at three different time points after moderate experimental TBI.
View Article and Find Full Text PDFPhysiol Behav
December 2024
Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran; Cognitive Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran. Electronic address:
Objectives: This study investigated the effects of environmental enrichment (EE) on the behavior and histological alterations of rats with barrel cortex damage.
Methods: Forty-eight adult male rats were divided into Control (Ctrl), Lesion, Lesion+EE.S (Lesion+Standard Enriched Environment, and Lesion+EE.
Brain Res
December 2024
Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Departamento de Ciências Morfológicas, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Congenital Zika Syndrome (CZS) is a condition that arises when a neonate presents with abnormalities resulting from Zika virus infection during gestation. While microcephaly is a prominent feature of the syndrome, other forms of brain damage are also observed, often accompanied by significant neurological complications. It is therefore essential to investigate the long-term effects of CZS, with special attention to sex differences, particularly concerning hippocampal function, given its vulnerability to viral infections.
View Article and Find Full Text PDFHum Exp Toxicol
December 2024
Department of neurology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China. Hubei Sizhen Laboratory, Affiliated Hospital of Hubei University of Chinese Medicine, Wuhan, China.
Introduction: The incidence of cerebral ischemia-reperfusion injury (I/R) is complex which seriously threatens the life safety of patients. Neither its prevention nor its treatment has been successful so far. Proteins that bind to DNA and belong to the C2/H2 zinc finger family are known as Krüppel-like factors (KLFs).
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