Lead induces oxidative stress, DNA damage and alteration of p53, Bax and Bcl-2 expressions in mice

Xu, Jin; Lian, Lingjun; Wu, Chen; Wang, Xiaofeng; Fu, Wenyu; Xu, Lihong

doi:10.1016/j.fct.2007.12.016

Cited by 159 publications

(86 citation statements)

References 42 publications

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“…Mechanisms of lead-induced liver injury include increased production of reactive oxygen species, and induced oxidative stress which results in DNA damage [43]. These reactive species interfere with cellular macromolecules and deactivates cellular antioxidant pool [44].…”

Section: Discussionmentioning

confidence: 99%

Hepatoprotective Effect of Sesame Oil against Lead Induced Liver Damage in Albino Mice: Histological and Biochemical Studies

Azab¹

2014

AJBIO

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Abstract:The liver performs many vital functions to eliminate toxins and harmful substances from the body. Hepatotoxic agents can react with the basic cellular components and consequently induce almost all types of liver lesions. The aim of this study was to investigate the possible hepatoprotective role of sesame oil against lead acetate induced hepatotoxicity in albino mice from the histological and biochemical aspects. In this study, thirty two adult male albino mice were used for this study and divided into four groups. The first group was control group, the 2 nd was the sesame oil group orally received sesame oil (5 ml/kg body wt.), the 3 rd group was the experimental and received lead acetate (500 mg /kg diet), the 4 th one co-administered lead acetate (500 mg/kg diet) with sesame oil (5 ml/kg body wt.) daily for 30 days. The livers were dissected out, weighted and specimens were taken and processed for light microscopic examinations. Blood samples were obtained for assessment of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and γ-glutamyltransferase activities, serum total proteins and albumin. Results indicate that, in lead treated animals, there were severe structural damage in the liver. The hepatocytes appeared irregularly arranged with disorganization of hepatic architecture. The hepatocytes appeared large with light and foamy cytoplasm filled with numerous vacuole-like spaces. The nuclei appeared with pyknotic nuclei. The central vein appeared dilated and congested with massive hemorrhage extending to the nearby cells. Also, there were focal degenerative and necrotic changes along with inflammatory cell infiltration. Decrease in body weight and increase in liver weight were observed. Biochemically, the serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyltransferase activities were increased and serum total proteins and albumin were decreased. Co-administration of sesame oil significantly improved the structural changes in the liver and also the serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and γ-glutamyltransferase activities were significantly declined and serum total proteins and albumin were elevated. Conclusion: It can be concluded that, the lead had adverse effects on the liver. Sesame oil showed effective hepatoprotective action against lead acetate induced hepatotoxicity in albino mice. So, the populations of high risk to lead should be advised to take sesame oil.

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Section: Discussionmentioning

confidence: 99%

Hepatoprotective Effect of Sesame Oil against Lead Induced Liver Damage in Albino Mice: Histological and Biochemical Studies

Azab¹

2014

AJBIO

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“…Besides the above-mentioned proteins, lead can induce metallothionein (MT), 44,45) heat shock protein 70 (HSP70), 41) pro-inflammatory protein cyclooxygenase-2 (COX-2), 46,47) pro-apoptotic protein Bax, 48,49) and glial fibrillary acidic protein (GFAP). 50) GFAP has been recently identified as a regulator of chaperone-mediated autophagy, 51) suggesting that the induction of GFAP serves to degrade aggregated proteins resulting from lead exposure.…”

Section: Stress Proteins and Genes Induced By Leadmentioning

confidence: 99%

Cellular Defense Mechanisms against Lead Toxicity in the Vascular System

Shinkai

Kaji

2012

Biological & Pharmaceutical Bulletin

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Lead is a toxic heavy metal that can cause a range of health problems. In this context, the vascular system is a particular target of the deleterious effects of lead. Lead exerts its toxicity through substitution of other divalent cations such as calcium and zinc, resulting in disruption of homeostasis. Based on the evidence that lead up-regulates endoplasmic reticulum (ER) chaperone glucose-regulated protein 78 (GRP78) and/or antioxidant proteins such as hemeoxygenase-1, it is believed that the heavy metal is able to induce ER and/ or oxidative stress in cells. These events also suggest that the unfolded protein response (UPR) system and the antioxidant defense system Kelch-like ECH-associated protein 1-nuclear factor (NF)-E2-related factor 2 (Keap1-Nrf2) play a critical role in adaptive response to lead. In this review, we summarize recent progress in lead toxicity in terms of cellular defense systems, including stress proteins and transcription factors involved in the vascular system.

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“…Rats of five group each were treated with three different lead dose levels of 25, 50, 100 mg/kg body weight (BW). The dose of the lead and the experimental paradigm of the current study were determined on the basis of the previous studies (Xu et al, 2008). Lead acetate was dissolved in saline (0.9% NaCl) with slightly acidic condition (as required) and administered intraperitoneally to animals at the doses of 25, 50 and 100 mg/kg body weight per day for 5 days consecutively.…”

Section: Animals and Lead Administrationmentioning

confidence: 99%

Increased DNA damage in blood cells of rat treated with lead as assessed by comet assay

Arif

Kabir

Hassan

et al. 2008

Bangladesh J Pharmacol

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Lead induces oxidative stress, DNA damage and alteration of p53, Bax and Bcl-2 expressions in mice

Cited by 159 publications

References 42 publications

Hepatoprotective Effect of Sesame Oil against Lead Induced Liver Damage in Albino Mice: Histological and Biochemical Studies

Hepatoprotective Effect of Sesame Oil against Lead Induced Liver Damage in Albino Mice: Histological and Biochemical Studies

Cellular Defense Mechanisms against Lead Toxicity in the Vascular System

Increased DNA damage in blood cells of rat treated with lead as assessed by comet assay

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