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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.

SUBMITTER: Al-Megrin WA

PROVIDER: S-EPMC7022878 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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

Al-Megrin Wafa A WA Alkhuriji Afrah F AF Yousef Al Omar S AOS Metwally Dina M DM Metwally Dina M DM Habotta Ola A OA Kassab Rami B RB Abdel Moneim Ahmed E AE El-Khadragy Manal F MF

Antioxidants (Basel, Switzerland) 20191221 1

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 ...[more]

PMID: 31877779

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Project description:The Acrylamide is a toxic compound generated under oxidative stress arising from intracellular ROS production and induced toxicity. It is frequently used in industry and generated through the heating of tobacco and foods high in carbohydrates. The exact mechanism of its toxicity is still unclear. In this study, an extract of the peels of pomegranate (Punica granatum L.), a nutritious and visually appealing fruit with a diverse bioactive profile, was examined for its potential anti-apoptotic, antioxidant, and anti-inflammatory effects. A total of 40 adult male Wistar rats were allocated into four groups of 10 rats each: Group 1 was a negative-control group (CNT) and received normal saline; Group 2 was a positive-control acrylamide group and received acrylamide orally at a dose of 20 mg/kg/bw; in Group 3, the rats were supplemented with pomegranate-peel extract (P.P; 150 mg/kg/bw) orally on a daily basis for 3 weeks, administered simultaneously with the acrylamide treatment described for Group 2; Group 4 was a protective group, and the animals received the pomegranate-peel extract and acrylamide as stated for Groups 2 and 3, with the pomegranate-peel extract (P.P. extract) administered 1 week earlier than the acrylamide. The results indicate that acrylamide exposure increased the serum levels of AST, ALT, creatinine, interleukin-1 beta, and interleukin-6 in an extraordinary manner. In addition, it increased the lipid peroxidation marker malondialdehyde (MDA) and simultaneously weakened antioxidant biomarker activities (SOD, GSH, and catalase) and reduced the levels of interleukin-10. The pomegranate-peel extract was shown to reduce the inflammatory blood markers of interleukin-1 beta and IL-6. Glutathione peroxidase, superoxide dismutase, catalase, and interleukin-10 were all significantly elevated in comparison to the acrylamide-treatment group as a result of the significant reduction in MDA levels induced by the P.P extract. In addition, the pomegranate-peel extract normalized the cyclooxygenase-2 (COX2), transforming growth factor-beta 1 (TGF-β1), and caspase-3 levels, with a significant upregulation of the mRNA expression of heme oxygenase-1 (HO-1), nuclear factor erythroid 2 (Nrf2), and Bcl-2. Therefore, these data reveal that pomegranate peel has anti-inflammatory, antiapoptotic, free-radical-scavenging, and powerful antioxidant activity that protects against acrylamide toxicity.

Project description:BackgroundThe heavy metals cause repro-toxicity via oxidative stress and suppress the antioxidant enzymes. Kaempferol and vitamin E possess antioxidant properties that can counteract the deleterious heavy metals effects.AimThe present study was directed to investigate the protective role of kaempferol, alone or with vitamin E, on testicular toxicity mediated by lead acetate in male rats.MethodsFifty adult male rats were randomly grouped into five groups (n = 10): the control group received 5 ml distilled water, and the Pb group was intraperitoneally injected with 20 mg/kg of lead acetate. The Pb + Vitamin E group received Pb with 100 mg/kg of vitamin E, the Pb + KAF group received Pb with 50 mg/kg of kaempferol, the Pb + KAF + Vitamin E group received Pb with kaempferol and vitamin E for 6 weeks.ResultsThe testicular levels of superoxide dismutase, catalase, steroidogenic enzyme, serum testosterone, follicle-stimulating hormone, interleukin (IL)-10, and sperm function were significantly decreased in the Pb group compared with all experimental groups. These parameters were significantly elevated in the Pb + KAF + Vitamin E group compared to other experimental groups. Lead acetate caused elevation in testicular malondialdehyde, nitric oxide, IL-6, IL-1β, tumor necrosis factor-α, nuclear factor kappa, and sperm abnormality compared to all treatment groups. All these parameters were significantly declined in the Pb + KAF + Vitamin E group and Pb + KAF group compared with the Pb group. The fold changes of pituitary follicle-stimulating hormone beta, gonadotropin-releasing hormone receptor, and luteinizing hormone beta, and testicular CYP11A1, LH receptor, and FHr gene expression were significantly upregulated in Pb + KAF + Vitamin E group compared with all experimental groups. In addition, KAF + Vitamin E has the potential to improve testicular regeneration in seminiferous tubules, Leydig, and Sertoli cells.ConclusionAdministration of kaempferol alone or with vitamin E can mitigate lead acetate-induced testicular toxicity in rats via its antioxidant and anti-inflammatory properties. The current research is the first to demonstrate that kaempferol can exert a preventive role in testicular dysfunction.

Dataset Information

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

Publications

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

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