Metabolic adaptability in liver and gastrocnemius muscle of mice following subacute lead toxicity

Abstract

Lead (Pb) is one of several environmental pollutants that adversely affect human health by producing toxicity at the tissue level. The aim of the study was to understand the effects of Pb on the metabolic profiles of liver and gastrocnemius muscle of mice in relation to carbohydrate and fat metabolisms. Swiss albino mice were chosen and divided into two groups, control and Pb-treated. The Pb-treated animals were exposed to Pb at a dose of 5 mg/kg body weight for 30 days orally, which resulted in hypoglycemia, glycosuria, and increased glycogenolysis in the liver and gastrocnemius muscle of treated mice. Pyruvic acid, the end product of glycolysis decreased in muscular tissue and increased in the liver. Additionally, the activity of G-6Pase was depressed in the liver, whereas lactate dehydrogenase activity was increased in skeletal muscle only. An adaptive mechanism was initiated by stimulating glycogenolytic and retarding glycolytic activity in the liver and also by alteration of liver and muscle pyruvate dehydrogenase activity along with increased activity of malate dehydrogenase in skeletal muscle. There was enhancement of succinate dehydrogenase and nicotinamide adenine dinucleotide phosphate oxidase activities in the studied tissues. Interestingly, cholesterol, high-density lipoprotein, and low-density lipoprotein levels were elevated, whereas those of triglycerides were decreased in Pb-treated mice serum. The activities of fatty acid synthase and glyceraldehyde 3 phosphate dehydrogenase were depressed in Pb-treated mice livers. Pb also significantly altered the morphological features of the liver, skeletal muscle, and pancreas. These data suggested that subacute Pb exposure was responsible for metabolic modulation in an adaptive fashion in the liver and skeletal muscle of mice.

Single and combined associations of blood lead and essential metals with serum lipid profiles in community-dwelling adults

“…The differences may be due to the different blood Pb levels of the participants in these studies and the non-linear relationship of Pb with TG. In animal experiments, similar conclusions were given (37,38). Mouse exposed to Pb (5 mg/kg body weight) for 30 days orally caused higher TC, LDL-C, HDL-C, and lower TG (37).…”

“…In animal experiments, similar conclusions were given (37,38). Mouse exposed to Pb (5 mg/kg body weight) for 30 days orally caused higher TC, LDL-C, HDL-C, and lower TG (37). The inverse U-shaped association of Pb with TG was also observed in the Wistar rats (38).…”

Lead exposure aggravates glucose metabolism disorders through gut microbiota dysbiosis and intestinal barrier damage in high‐fat diet‐fed mice

“…[51][52][53] We did not measure Pb levels in the blood, which is a limitation of our work. A study by Das et al 54 found that Pb had a direct inhibitory effect on hepatic gluconeogenic genes glucose-6 phosphatase expression. Therefore, we speculate that the decreased HOMA-IR in ND mice by Pb exposure may be related to the inhibition of gluconeogenesis.…”

“…We did not measure Pb levels in the blood, which is a limitation of our work. A study by Das et al 54 . found that Pb had a direct inhibitory effect on hepatic gluconeogenic genes glucose‐6 phosphatase expression.…”

Moderate selenium mitigates hand grip strength impairment associated with elevated blood cadmium and lead levels in middle-aged and elderly individuals: insights from NHANES 2011–2014

“…Animal experiments indicate that the toxic effects of Pb on muscles primarily manifest in disrupting normal glucose metabolism processes, altering the activity of key enzymes, and adjusting energy metabolism, which may also damage muscle tissue structure. These physiological changes could negatively impact muscle function and quality, thereby adversely affecting overall health (Das et al, 2020). In another animal study, it was found that Pb exposure's harm to skeletal muscle function mainly includes reduced muscle mass, decreased exercise capacity, weakened muscle strength, disrupted lipid metabolism, increased inflammatory responses, and upregulated expression of pro-apoptotic genes.…”