Endosulfan induces cardiotoxicity through apoptosis via unbalance of pro-survival and mitochondrial-mediated apoptotic pathways

Wei, Jialin; Liu, Jianhui; Zhang, Lianshuang; Zhu, Yupeng; Li, Xiangyang; Zhou, Guang‐Peng; Zhao, Yanzhi; Sun, Zhiwei; Zhou, Xianqing

doi:10.1016/j.scitotenv.2020.138790

Cited by 12 publications

(9 citation statements)

References 52 publications

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“…LPO is initially carried out by free radicals and leads to cellular damage by deactivating membrane enzymes, depolymerization of polysaccharides and breakdown of proteins. Tissue injuries in rats and rabbits due to the exposure of pyrethroids have already been reported [ 41 , 42 ]. Our results ( Figure 1 ) clearly demonstrate that Cyp toxicity caused a marked rise in LPO with a reduction in antioxidant enzyme activity (SOD, CAT) in the liver.…”

Section: Discussionmentioning

confidence: 99%

Hepatoprotective Effect of Curcumin Nano-Lipid Carrier against Cypermethrin Toxicity by Countering the Oxidative, Inflammatory, and Apoptotic Changes in Wistar Rats

et al. 2023

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This study investigated the potential hepatoprotective activity of curcumin-incorporated nano-lipid carrier (Cur-NLC) against cypermethrin (Cyp) toxicity in adult Wistar male rats. All animals in groups III, IV, V, and VI were subjected to Cyp (50 mg/kg) toxicity for 15 days. Three different doses of Cur-NLC (1, 2.5, and 5 mg/kg/day) were administered orally for 10 days. The toxic effects were evaluated considering the increases in serum hepatic biomarkers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein and albumin, and lipid peroxidation (LPO), as well as a decrease in antioxidative activity (reduced glutathione (GSH), superoxide dismutase (SOD), and catalase) and the upregulation of inflammatory cytokines (IL-1β, IL-6, and TNF-α). Immunohistochemistry studies of proteins (NF-κB, Apaf-1, 4-HNE, and Bax) showed enhanced expression, and histopathological examination revealed architectural changes in liver cells, indicating liver toxicity in animals. Toxicity was determined by quantitative and qualitative determinations of DNA fragmentation, which show massive apoptosis with Cyp treatment. The administration of Cur-NLC significantly ameliorates all changes caused by Cyp, such as a decrease in the levels of serum liver markers, an increase in antioxidative parameters, a decrease in expression of inflammatory cytokines (IL-1β, IL-6, TNF-α, and NF-κB), and apoptosis (caspases-3, 9, Apaf-1, 4-HNE, and Bax), according to calorimetric and immunohistochemistry studies. The smear-like pattern of DNA is ameliorated similarly to the control at a high dose of Cur-NLC. Furthermore, all histopathological changes were reduced to a level close to the control. In conclusion, Cur-NLC could be a potent nutraceutical that exhibits a hepatoprotective effect against Cyp-induced hepatotoxicity in rats.

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Section: Discussionmentioning

confidence: 99%

Hepatoprotective Effect of Curcumin Nano-Lipid Carrier against Cypermethrin Toxicity by Countering the Oxidative, Inflammatory, and Apoptotic Changes in Wistar Rats

et al. 2023

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“…27,28 In addition, mitochondrial dysfunction promotes caspase-9 activation, leading to apoptosis via cleaved caspase-3. 29 Consequently, mitochondria-mediated apoptotic pathway activation may be responsible for the increase in cleaved caspase-3 via caspase-9 upregulation. This study has several limitations.…”

Section: Discussionmentioning

confidence: 99%

“…Mitochondria, the main caspase‐9 regulator, deteriorate and become dysfunctional during immobilization 27,28 . In addition, mitochondrial dysfunction promotes caspase‐9 activation, leading to apoptosis via cleaved caspase‐3 29 . Consequently, mitochondria‐mediated apoptotic pathway activation may be responsible for the increase in cleaved caspase‐3 via caspase‐9 upregulation.…”

Section: Discussionmentioning

confidence: 99%

Myonuclear apoptosis via cleaved caspase‐3 upregulation is related to macrophage accumulation underlying immobilization‐induced muscle fibrosis

et al. 2021

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Introduction/Aims: Although macrophage accumulation plays a key role in the development of immobilization-induced muscle fibrosis, the underlying mechanisms remain unclear.Therefore, we focused on the alterations of myonuclear apoptosis via cleaved caspase-3, and investigated whether these changes may be related to macrophage accumulation.Methods: Eight-week-old Wistar rats were divided into immobilization and control groups, and the soleus muscles were selected for analysis. Results:The mRNA and protein expression of collagen and the number of CD11bpositive cells were significantly higher in the immobilized rats than in the control rats at 1 and 2 weeks. TdT-mediated dUTP nick end-labeling (TUNEL)-positive myonuclei counts in 1-and 2-week control rats were 0.2 ± 0.1 and 0.2 ± 0.5, whereas they were 1.0 ± 0.6 and 1.1 ± 0.5 in 1-and 2-week immobilized rats. The cleaved caspase-3 protein expressions in 1-and 2-week control rats were 0.2 ± 0.1 and 0.2 ± 0.1, whereas they were 0.5 ± 0.1 and 0.4 ± 0.2 in 1-and 2-week immobilized rats. TUNEL-positive myonuclei counts and cleaved caspase-3 protein expression were significantly higher in immobilized rats than in control rats at 1 and 2 weeks. The numbers of myonuclei in 1-and 2-week control rats were 2.8 ± 0.1 and 2.6 ± 0.4, whereas they were 2.2 ± 0.4 and 2.2 ± 0.2 in 1-and 2-week immobilized rats. The numbers of myonuclei were significantly lower in immobilized than in control rats at both time-points.Discussion: Myonuclear apoptosis via the upregulation of cleaved caspase-3 might induce macrophage accumulation. These alterations are related to immobilizationinduced muscle fibrosis.

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“…3 Nowadays, research reports indicate that pesticide exposure results in several diseases of the nervous system, kidney, and heart, as well as being a cause of cancer. 4,5 Of numerous environmental pollutants, cypermethrin (Cyp) is the most commonly used insecticide. It has been used for commercial and household purposes because of its high insecticidal properties.…”

Section: Introductionmentioning

confidence: 99%

“…6 Cyp has a cynao group at the α-carbon of the alcohol group, so belongs to pyrethroids type-II. 4 Most of the Cyp is absorbed into our body by absorption through the digestive tract. Both cis and trans isomers of Cyp are broken down into cyclopropanecarboxylic acid and phenoxybenzoic acid.…”

Section: Introductionmentioning

confidence: 99%

Cardioprotective Effects of Nano-Piperine Against Cypermethrin Toxicity Through Oxidative Stress, Histopathological and Immunohistochemical Studies in Male Wistar Rats

Hussain

Ashafaq

Alshahrani

et al. 2023

Natural Product Communications

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Background: Cypermethrin (Cyp) is a synthetic derivative of pyrethroids, implicated in various organ toxicity. This study investigated the potential cardio-protective activity of nano-piperine (NP) against Cyp toxicity in adult Wister male rats. Methods: All animals in groups II, III, IV, and V were subjected to Cyp (50 mg/kg) for 15 days. After 1 h of receiving the Cyp dose, 3 doses of NP (125, 250, and 500 µg/kg/day) were administered to groups III, IV, and V, respectively, for 10 days. In Group VI, a dose of 500 µg/kg NP alone was given orally daily for 10 days. Result: The toxic effects were evaluated by an increase in serum cardiac injury biomarkers (lactate dehydrogenase, cardiac troponin I, creatine kinase-myoglobin binding, tissue lipid peroxidation, a decrease in antioxidative activity, such as glutathione, superoxide dismutase [SOD] and catalase, and upregulation of interleukins [interleukin 1β, interleukin 6]). Immunohistochemistry studies of proteins (nuclear factor-κB [NF-kB], apoptotic protease activating factor-1 [Apaf-1], 4-hydroxynonenal [4-HNE] and Bax) showed enhanced expression, and histopathological examination revealed myolysis, loss of striation and hemorrhages indicating heart toxicity in the animals. Administration of NP significantly ameliorated all the changes caused by Cyp, such as a decrease in the levels of serum cardiac injury markers, an increase of antioxidative parameters, decrease in expression of inflammatory cytokines and NF-kB, Apaf-1, 4-HNE, and Bax, as shown by immunohistochemistry studies. Furthermore, all the histopathological changes were reduced to near the values of the control. Conclusion: Collectively our findings indicated that NP could be a potent nutraceutical exhibiting cardioprotective effects against Cyp-induced cardiotoxicity in rats.

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Endosulfan induces cardiotoxicity through apoptosis via unbalance of pro-survival and mitochondrial-mediated apoptotic pathways

Cited by 12 publications

References 52 publications

Hepatoprotective Effect of Curcumin Nano-Lipid Carrier against Cypermethrin Toxicity by Countering the Oxidative, Inflammatory, and Apoptotic Changes in Wistar Rats

Hepatoprotective Effect of Curcumin Nano-Lipid Carrier against Cypermethrin Toxicity by Countering the Oxidative, Inflammatory, and Apoptotic Changes in Wistar Rats

Myonuclear apoptosis via cleaved caspase‐3 upregulation is related to macrophage accumulation underlying immobilization‐induced muscle fibrosis

Cardioprotective Effects of Nano-Piperine Against Cypermethrin Toxicity Through Oxidative Stress, Histopathological and Immunohistochemical Studies in Male Wistar Rats

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