Antagonistic Efficacy of Luteolin against Lead Acetate Exposure-Associated with Hepatotoxicity is Mediated via Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Activities

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.

Elucidation of the Molecular Mechanisms Underlying Sorafenib-Induced Hepatotoxicity

“…Several reports have suggested alterations in liver enzymes such as ALP, AST, ALT, and urea and dysregulation of blood-associated proteins and lipids as reliable indicators of drug-mediated hepatotoxicity [30][31][32][33][34]. In the current study, SORA treatment significantly induced plasma levels of ALT and ALP, but not AST, while decreasing plasma levels of albumin, consistent with previously published reports [33,35,36]. Data from our current study demonstrated that SORA resulted in remarkable changes in cholesterol and LDL levels, and had no significant effects on triglyceride, HDL, or VLDL levels.…”

Antioxidant and Compositional HPLC Analysis of Three Common Bamboo Leaves

“…Flavonoids and phenolic acids are natural antioxidants found in plants, and have been reported on bamboo leaves [13,14]. Bamboo leaves contain a lot of flavonoids [15][16][17], such as chlorogenic acid (CA) [18], isoorientin (iso-ORI) [19] and orientin (ORI) [20], isovitexin (iso-VIT), Cynaroside (CYN) [21], Luteolin (LUT) [22,23], and Apigenin (API) [24]. These ingredients have effects on oxidation, diabetes, cardiovascular disease, inflammation, and so on.…”

Red Beetroot Extract Abrogates Chlorpyrifos-Induced Cortical Damage in Rats

“…Of all the body organs, the brain has the closest association with the progression of oxidative stress conditions due to its high lipid content, low antioxidant molecule level, and high oxygen consumption [36]. Exposure to environmental toxicants causes neuronal damage and behavioral deficits [37].…”