Anti-apoptotic role of spermine against lead and/or gamma irradiation-induced hepatotoxicity in male rats

Abu-Khudir, Rasha; Habieb, Mahmoud E.; Mohamed, Marwa Abd El Hameed; Hawas, Asrar M.; Mohamed, Tarek M.

doi:10.1007/s11356-017-0069-0

Cited by 10 publications

(4 citation statements)

References 102 publications

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“…Hepatocyte apoptosis occurs through two main pathways: the extrinsic pathway, which depends on signals from the death receptor, and the intrinsic pathway, which is triggered by intracellular stimuli. In agreement with previous studies, Pb exposure was associated with an induction of cell apoptotic mediators and a marked disturbance in the gene expression of apoptosis-regulating proteins [7,47,66]. The apoptosis induced by Pb exposure may result from the damage of the mitochondrial membrane allowing the release of cytochrome-c and caspase-activating factors into the cytosol.…”

Section: Discussionsupporting

confidence: 91%

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

et al. 2019

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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.

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Section: Discussionsupporting

confidence: 91%

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

et al. 2019

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“…52 There are many apoptotic pathways, among which the mitochondrial pathway plays an important role in Pb-induced liver cell apoptosis. 53 The Bcl-2 proto-oncogene has antiapoptotic activity induced by various stimuli. 54 Bcl-2 inhibits the release of CytC in mitochondria by affecting the external permeability of mitochondria, while Bax can form channels on the mitochondrial membrane to help release CytC into the cytoplasm and then activate downstream Caspase-9 and Caspase-3, leading to cell apoptosis.…”

Section: ■ Discussionmentioning

confidence: 99%

“…Mitochondria are the main source of ROS in cells and are organelles that interfere with oxidative damage . There are many apoptotic pathways, among which the mitochondrial pathway plays an important role in Pb-induced liver cell apoptosis . The Bcl-2 proto-oncogene has antiapoptotic activity induced by various stimuli .…”

Section: Discussionmentioning

confidence: 99%

Quercetin and Allicin Can Alleviate the Hepatotoxicity of Lead (Pb) through the PI3K Signaling Pathway

Cai

Cao

Bai

et al. 2021

J. Agric. Food Chem.

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Lead (Pb) is a common toxic heavy metal pollutant in the environment that seriously endangers the health of animals. The liver is a key target organ affected by Pb toxicity. Plant extracts allicin and quercetin have a strong antioxidant capacity that can promote the excretion of heavy metals by improving the body’s antioxidant defense and chelating heavy metal ions. To explore the preventive and therapeutic effects of allicin and quercetin on Pb poisoning in chickens, 96 chickens were randomly divided into eight groups: control, Pb, allicin, quercetin, allicin + quercetin, Pb + allicin, Pb + quercetin, and Pb + allicin + quercetin groups. The chickens were given feed containing the above treatments for 90 days. The results indicated that Pb can affect the growth and development of the liver, damage the circulatory system, destroy the structure of mitochondria and nuclei in liver cells, cause an imbalance in the oxidation system, inhibit PI3K protein, and activate the mitochondrial apoptotic pathway. Allicin and quercetin, alone or in combination, can improve the antioxidant capacity of the liver and alleviate liver tissue damage caused by Pb. In summary, allicin and quercetin could alleviate oxidative damage and apoptosis in the Pb-poisoned chicken liver through the PI3K signaling pathway, with stronger effects achieved by their combination.

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“…Currently, only four cytokine-based medical countermeasures, including Filgrastim, Neulastat, Sargramostim, and Romiplostim, have been approved by the Food and Drug Administration (FDA) as radiomitigators to improve survival in patients received a myelosuppressive dose of radiation [ 11 ]. However, no radioprotector has received approval from FDA; it is imperative to explore and develop novel drugs for HSC protection and restoration after ionizing radiation (IR) [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Fluacrypyrim Protects Hematopoietic Stem and Progenitor Cells against Irradiation via Apoptosis Prevention

Zhang,

Qiao,

Guan

et al. 2024

Molecules

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Ionizing radiation (IR)-induced hematopoietic injury has become a global concern in the past decade. The underlying cause of this condition is a compromised hematopoietic reserve, and this kind of hematopoietic injury could result in infection or bleeding, in addition to lethal mishaps. Therefore, developing an effective treatment for this condition is imperative. Fluacrypyrim (FAPM) is a recognized effective inhibitor of STAT3, which exhibits anti-inflammation and anti-tumor effects in hematopoietic disorders. In this context, the present study aimed to determine whether FAPM could serve as a curative agent in hematopoietic-acute radiation syndrome (H-ARS) after total body irradiation (TBI). The results revealed that the peritoneally injection of FAPM could effectively promote mice survival after lethal dose irradiation. In addition, promising recovery of peripheral blood, bone marrow (BM) cell counts, hematopoietic stem cell (HSC) cellularity, BM colony-forming ability, and HSC reconstituting ability upon FAPM treatment after sublethal dose irradiation was noted. Furthermore, FAPM could reduce IR-induced apoptosis in hematopoietic stem and progenitor cells (HSPCs) both in vitro and in vivo. Specifically, FAPM could downregulate the expressions of p53-PUMA pathway target genes, such as Puma, Bax, and Noxa. These results suggested that FAPM played a protective role in IR-induced hematopoietic damage and that the possible underlying mechanism was the modulation of apoptotic activities in HSCs.

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Anti-apoptotic role of spermine against lead and/or gamma irradiation-induced hepatotoxicity in male rats

Cited by 10 publications

References 102 publications

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

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

Quercetin and Allicin Can Alleviate the Hepatotoxicity of Lead (Pb) through the PI3K Signaling Pathway

Fluacrypyrim Protects Hematopoietic Stem and Progenitor Cells against Irradiation via Apoptosis Prevention

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