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Mitochondrial Stress and Cellular Senescence
Published in Shamim I. Ahmad, Handbook of Mitochondrial Dysfunction, 2019
Irene L. Tan, Michael C. Velarde
Mitochondrial stress induces cellular senescence, also referred to as mitochondrial dysfunction-associated senescence (MiDAS) (Wiley et al. 2016). Mitochondrial stress due to oxidative damage decreases the total number of functional mitochondria or impair function of the mitochondrial electron transport chain (ETC), resulting in decreased ATP production and reduced mitochondrial function (Nicolson 2014). Inhibition of mitochondrial electron transport complex I by rotenone causes cellular aging in normal human fibroblasts and primary mouse cells (Miwa et al. 2014; Moiseeva et al. 2009). Inhibition of complex II activity by down-regulating expression of iron-sulfur subunit also promotes premature senescence (Yoon et al. 2003). Likewise, exposure to the complex III inhibitor antimycin A and the complex V inhibitor oligomycin A are linked to cellular senescence, as observed by up-regulation of p16, p21, and p27- CDK inhibitors (CDKIs) (Stöckl et al. 2006). Knockdown of the Rieske iron sulfur protein (RISP), which transfers electrons from ubiquinol to cytochrome c1 in complex III of the ETC, also triggers the senescence phenotype (Moiseeva et al. 2009).
Agrochemicals: A Brief Overview
Published in Dongyou Liu, Handbook of Foodborne Diseases, 2018
Rotenone is a “natural” insecticide derived from the roots of Derri Elliptica and from those of Lonchocarpus urucu and is used particularly in organic farming (103). It is very toxic to fish, and indeed root extracts were used to paralyze fish for capture and consumption. The toxicity of rotenone is due to its ability to inhibit the mitochondrial respiratory chain at the level complex I (104). Acute intoxication with rotenone is rare, and poisoning symptoms include initial increased respiratory and cardiac rates, clonic and tonic spasms, and respiratory depression. In recent years, however, rotenone has received much attention because of its potential role in the etiology of Parkinson disease. Administration of rotenone to rats (2–3 mg/kg/day for 1–5 weeks) causes selective nigrostriatal degeneration as well as protein inclusions similar to Lewy bodies, that stain positively for ubiquitin and α-synuclein (105,106). An association between use of rotenone and increased risk of Parkinson disease has been reported (36), though the role of rotenone in the etiology of Parkinson disease in the general population is still being debated (107).
Ethnobotany of the Neem Tree (Azadirachta Indica a. Juss): A Review
Published in T. Pullaiah, K. V. Krishnamurthy, Bir Bahadur, Ethnobotany of India, 2017
K. Sri Rama Murthy, T. Pullaiah, Bir Bahadur, K. V. Krishnamurthy
In Africa and Caribbean, users of this plant, especially children, eat ripe fruits of Neem. In India, since ancient times the tender leaves of Neem are consumed as food and for tea preparations. Domestic animals are also fed with Neem leaves (Hedge, 1993). Despite A. indica being known for its pesticidal properties there are no records of Neem toxicity to humans, probable by avoiding higher doses. In fact, it was observed that, toxic effects of Neem oil in mammals occur only at higher doses (Deng et al., 2013). This toxicity is not lower compared to the natural compound rotenone (largely used as a broad spectrum insecticide, piscicide and pesticide) (Coats, 1994). Woollen and other cloths are stored with dried neem leaves, due to insecticidal properties as also various cereals and other grains for long term storage.
Metformin protects red blood cells against rotenone induced oxidative stress and cytotoxicity
Published in Archives of Physiology and Biochemistry, 2021
Shambhoo Sharan Tripathi, Abhishek Kumar Singh, Farhan Akhtar, Ankita Chaudhary, Syed Ibrahim Rizvi
The present investigation was undertaken to evaluate the anti-oxidative potential of metformin to limit rotenone-induced toxicity in blood. Rotenone is a widely used plant-derived broad-spectrum pesticide (piscicide, acaricide, and insecticide). Being extremely hydrophobic, rotenone can easily cross biological membranes, apparently without a transport system (Esteve-Rudd et al.2011). According to WHO classification, rotenone is a dangerous Class II pesticide. Rotenone induces toxicity through ROS over-production and oxidative stress (Sherer et al.2003), which further leads to a neurodegenerative disorder like Parkinson’s disease (PD) (Tanner et al.2011). It has also been observed that rotenone induces eryptosis, a common cell death mechanism of erythrocytes. In addition, it induces cell membrane scrambling that results in erythrocytes shrinkage (Lupescu et al.2012). As a consequence, rotenone toxicity may lead to premature removal of circulating erythrocytes (Jelkmann 2012). The disproportionate eryptosis may also lead to anaemia (Lang et al.2008), significantly a higher incidence of anaemia has been reported in patients with PD (Kasten et al.2010). The anaemia could also be an early symptom for other neurological disorders (Kasten et al.2010, Savica et al.2010).
Optical coherence tomography in the investigation of systemic neurologic disease
Published in Clinical and Experimental Optometry, 2019
Sangeetha Srinivasan, Nathan Efron
In rodents, a rotenone‐induced Parkinson's disease model has been utilised for an improved understanding of the disease. Rotenone is a pesticide used by farmers, but is found to exert neurotoxic effects that produce characteristics that closely resemble clinical features of Parkinson's disease. Rotenone used in vivo or in vitro, when administered by subcutaneous, intravenous or intraperitoneal routes, causes selective inhibition of mitochondrial complex 1, increased oxidative stress, and release of free radicals. There is also a decrease in adenosine triphosphate synthesis, leading to selective degeneration of the nigrostriatal dopamine system, which produces features of clinical Parkinson's disease.
Agaricus blazei extract attenuates rotenone-induced apoptosis through its mitochondrial protective and antioxidant properties in SH-SY5Y neuroblastoma cells
Published in Nutritional Neuroscience, 2018
Veerappan Venkatesh Gobi, Srinivasagam Rajasankar, Muthu Ramkumar, Chinnasamy Dhanalakshmi, Thamilarasan Manivasagam, Arokiasamy Justin Thenmozhi, Musthafa Mohamed Essa, Ranganathan Chidambaram
Rotenone is a naturally occurring pesticide derived from the roots of genera Derris and Lonchocarpus, which is widely used as an insecticide and fish poison. Similar to other dopaminergic neurotoxin models, rotenone has been suggested to inhibit complex I of the mitochondrial respiratory chain. Within complex I, upstream from the rotenone binding site, is a site of electron leak that can enhance ROS formation.13 Oxidative stress may contribute to the neurodegeneration observed in PD.14 Further downstream, mitochondrial damage and oxidative toxicity leads to the release of cytochrome c (cyto c) and caspase 3 activation, that ends in apoptosis.11,12,15,16