Chronic exposure to low doses of Pb induces hepatotoxicity at the physiological, biochemical, and transcriptomic levels of mice

Abstract

Lead (Pb), a non-essential heavy metal, is a major global environmental contaminant with serious toxicological consequences. In the present study, the effects on hepatotoxicity of mice with chronic exposure to low doses of Pb were evaluated. While oral exposure to 0.03 or 0.1 mg/L Pb for 15 weeks in male adult mice had no significant effect on body weights, Pb exposure resulted in liver histopathological effects and increase of hepatic activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). In addition, hepatic reactive oxygen species (ROS) and malondialdehyde (MDA) significantly accumulated after treatment. Conversely, glutathione (GSH) decreased significantly in both 0.03 and 0.1 mg/L Pb-treated groups. Moreover, the hepatic activities of superoxide dismutase 1 (SOD) and catalase (CAT) increased significantly following treatment with 0.1 mg/L Pb for 15 weeks, concomitant with increases in transcriptions of hepatic Sod, Cat, and Gpx. Furthermore, transcriptions of hepatic metallothionein (MT), zinc transporter 5 (Znt5) and copper transporter 1 (Ctr1), and subsequent protein levels were also increased in liver of mice when exposed to 0.1 mg/L Pb for 15 weeks. In addition, the transcriptome data showed that Pb has substantial influence on several pathways, including PPAR signaling pathways, AMPK signaling pathways, fatty acid metabolism, and drug metabolism. Our data suggested that chronic Pb exposure could induce hepatotoxicity at the physiological, biochemical, and transcriptomic levels in mice. K E Y W O R D Shepatotoxicity, oxidative stress, gene expression, Pb

Aluminum, Arsenic, Beryllium, Cadmium, Chromium, Cobalt, Copper, Iron, Lead, Mercury, Molybdenum, Nickel, Platinum, Thallium, Titanium, Vanadium, and Zinc: Molecular Aspects in Experimental Liver Injury

“…Lead (Pb for Latin plumbum) overdose in animals caused experimental liver injury. Elucidating its pathogenic background was challenging as some issues remain controversial, although many studies have been published [ 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 ]. Consensus exists among experts that ROS as a product of oxidative stress plays a major role in initiating the injury process [ 12 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ].…”

“…Consensus exists among experts that ROS as a product of oxidative stress plays a major role in initiating the injury process [ 12 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ]. Pb binds to sulfhydryl groups of structural proteins or any cytosolic protein such as glutathione, thereby reducing the antioxidant defense property and enhancing the Pb toxicity [ 64 , 65 , 67 , 68 , 70 , 71 ] through lipid peroxidation of cell membranes, such as of mitochondria or endoplasmic reticulum [ 12 , 64 , 65 , 66 , 70 , 72 ]. The high affinity of Pb to protein sulfhydryl groups resulted in lower activities of a number of enzymes like catalase, glutathione peroxidase, glucose-6-phosphate dehydrogenase, and superoxide dismutase [ 65 , 72 ].…”

Effects of Heavy Metal Exposure from Leather Processing Plants on Serum Oxidative Stress and the Milk Fatty Acid Composition of Dairy Cows: A Preliminary Study

“…Fatty acids can be useful biomarkers in the determination of the role of the altered synthesis of eicosanoids in the mechanisms of altered bone metabolism associated with abnormal exposures to lead (Pb) and other heavy metals [ 22 ]. Several studies have shown a relationship between elevated tissue Pb and both oxidative stress biomarkers and fatty acid composition [ 23 , 24 , 25 , 26 ]. Lead exposure has been shown to alter the ω-3 polyunsaturated fatty acids (PUFAs) and ω-6 PUFAs composition of milk in rats [ 27 ].…”

SIRT1/mTOR pathway‐mediated autophagy dysregulation promotes Pb‐induced hepatic lipid accumulation in HepG2 cells

“…Lead (Pb) is one of the most pervasive and non‐biodegradable toxic heavy metals and has resulted in significant public health problems around the world 1 . It can be obtained from Pb pollution, inhalation of dust particles as well as contaminated food and water ingestion and might result in several toxicological effects targeting multiple organs and tissues including liver, 2 gastrointestinal, 3 renal, 4 lung, 5 bone 6 and nervous, 7 hematopoietic, 8 reproductive, 9 cardiovascular systems 10 . The toxicity of Pb is particularly insidious and may cause irreversible health effects, and there is no such level of Pb exposure that appears to be safe.…”