Abstract
The abundant use of lead (Pb; toxic heavy metal) worldwide has increased occupational and ecosystem exposure, with subsequent negative health effects. The flavonoid luteolin (LUT) found in many natural foodstuffs possesses antioxidant and anti-inflammatory properties. Herein, we hypothesized that LUT could mitigate liver damage induced by exposure to lead acetate (PbAc). Male Wistar rats were allocated to four groups: control group received normal saline, LUT-treated group (50 mg/kg, oral, daily), PbAc-treated group (20 mg/kg, i.p., daily), and LUT+PbAc-treated group (received the aforementioned doses via the respective routes of administration); the rats were treated for 7 days. The results revealed that PbAc exposure significantly increased hepatic Pb residue and serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin value. Oxidative reactions were observed in the liver tissue following PbAc intoxication, characterized by the depletion and downregulation of antioxidant proteins (glutathione, glutathione reductase, glutathione peroxidase, superoxide dismutase, catalase, nuclear factor erythroid 2-related factor 2, and heme oxygenase-1), and an increase in oxidants (malondialdehyde and nitric oxide). Additionally, PbAc increased the release and expression of the pro-inflammatory cytokines (tumor necrosis factor alpha and interleukin-1 beta), inducible nitric oxide synthase, and nuclear factor kappa B. Moreover, PbAc enhanced hepatocyte loss by increasing the expression of pro-apoptotic proteins (Bax and caspase-3) and downregulating the anti-apoptotic protein (Bcl-2). The changes in the aforementioned parameters were further confirmed by noticeable histopathological lesions. LUT supplementation significantly reversed all of the tested parameters in comparison with the PbAc-exposed group. In conclusion, our findings describe the potential mechanisms involved in the alleviation of PbAc-induced liver injury by luteolin via its potent anti-inflammatory, antioxidant, and anti-apoptotic properties.
Highlights
The liver is a vital organ involved in many significant biological functions, such as nutritional balance, glucose and cholesterol metabolism, and synthesis of clotting factors
Oral administration of LUT to rats did not affect their food and water consumption, whereas the PbAc-injected group exhibited a significant decline in food intake, resulting in a marked decrease in the animals’ body weight (Supplementary data Table S1)
Rats injected with Pb exhibited high MDA content in liver homogenates, and these results were in agreement with the elevated ALT and AST activities and the findings reported by other studies [39,47,56]
Summary
The liver is a vital organ involved in many significant biological functions, such as nutritional balance, glucose and cholesterol metabolism, and synthesis of clotting factors. Owing to its substantial blood supply, the liver is responsible for metabolizing potentially toxic xenobiotics, rendering it vulnerable to toxic injury [1]. Lead (Pb) is a non-essential persistent metal with colorless, tasteless, and odorless characteristics. It persists in the environment for a long time and can be detected at harmful concentrations in the environment and living organisms [2]. Post-mortem examination of human bodies has revealed that the liver is the main storehouse of Pb, storing approximately one third of the total absorbed lead, followed by the kidney [4]
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