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Immunomodulatory Effect of Plant-Based Extracts on Neurodegeneration
Published in P. Mereena Luke, K. R. Dhanya, Didier Rouxel, Nandakumar Kalarikkal, Sabu Thomas, Advanced Studies in Experimental and Clinical Medicine, 2021
Koel Sinha, Chitrangada Das Mukhopadhyay
Mitochondrial‑Mediated Neurodegeneration: Manifestations of neurodegenerative diseases such as AD, PD, HD, MS, and ALS are largely associated with mitochondrial damage [13–16]. Several mitochondrial-dependent mechanisms such as inhibition of mitochondrial electron transport chain (ETC)’s complexes, ROS generation, and impairment of mitochondrial dynamics could contribute to the pathogenesis of neuronal injury as well as neurodegenerative diseases [17, 18]. Mitochondrial abnormalities and defective ETC (Complex I) present in substantia nigra is the foremost cause of neuronal damage in AD, PD, and ALS whereas, neuronal damage in MS is also attributed to Complex I and IV of the ETC along with the loss of mitochondrial membrane potential (ΔΨm) [19, 20]. Furthermore, evidences from clinical studies suggested the active role of mitotoxicity in the neuronal degeneration in HD [13]. Huntingtin, the gene responsible for HD, is reported to directly impair the mitochondrial functions [21]. Based on these findings it can be concluded that mitochondrial damage is the primary event observed in various neurodegenerative diseases. Owing to complex interplay between mitochondrial-toxicity and oxidative stress, it has been unclear whether mitochondrial damage is the main consequence of neuronal damage. Evidences also proved that mitotoxicity-related oxidative stress is also the leading cause for the development of neurodegeneration.
Developing a Toxicology Evaluation Plan for Transdermal Delivery Systems
Published in Francis N. Marzulli, Howard I. Maibach, Dermatotoxicology Methods: The Laboratory Worker’s Vade Mecum, 2019
Mary E. Prevo, Michel Cormier, James Matriano
Two assays—the Neutral Red Assay and the mitochondrial toxicity test (MTT) —are drawing increasing interest despite some limitations and offer ease of application, objectivity, and the opportunity for automation. The Neutral Red Uptake Assay assesses the integrity of the lysosomal compartment (Bulychev et al., 1978). One drawback of this assay is the potential interference with lysosomotropic agents and ionophores (Reijngoud and Tager, 1976; Cramb, 1986). The modified MTT is used to screen in vitro cytotoxicity of agents on human keratinocytes (Swisher et al., 1989). The assay is unsuitable for the following materials: (1) substances that spontaneously reduce MTT, including glutathione and other sulfhydryl-containing molecules; (2) those that inhibit the mitochondrial dehydrogenases responsible for metabolizing MTT. A recently introduced tetrazolium salt, XTT, does not require formazan solubilization prior to absorbance measurements (Roehm et al., 1991).
Human Immunodeficiency Virus Infection
Published in Thomas T. Yoshikawa, Shobita Rajagopalan, Antibiotic Therapy for Geriatric Patients, 2005
Chronic hyperlactatemia can occur with NRTIs. Cases of severe lactic acidosis with hepatomegaly and steatosis are rare but associated with a high mortality rate. This may be related to mitochondrial toxicity. Nevirapine, an NNRTI, has the greatest potential for causing clinical hepatitis.
Safety of current antiviral drugs for chronic hepatitis B
Published in Expert Opinion on Drug Safety, 2022
Chiara Masetti, Nicola Pugliese, Alessio Aghemo, Mauro Viganò
Nucleos(t)ide analogues approved for the treatment of CHB suppress viral replication by inhibiting the HBV DNA polymerase activity. The effect of NUCs on human nuclear DNA polymerase, which is responsible for human gene replication and repair, is weak and negligible. On the other hand, their activity against mitochondrial DNA (mtDNA) polymerase is not totally insignificant, as its functionality may be compromised when the intracellular concentration of NUCs exceeds a critical threshold [12]. As a consequence, mitochondrial dysfunction with inhibition of the respiratory chain, accumulation of lactic acid, and production of reactive oxygen species may develop [11–13]. Clinical manifestations of mitochondrial toxicity are variable and essentially affect organs and tissues whose function is closely linked to mitochondrial activity. They include nephropathy, myopathy, peripheral neuropathy, hepatic steatosis, pancreatitis, and lactic acidosis [12,14]. Mitochondrial toxicity is influenced by some host cofactors such as age, gender and medical comorbidities [12].
Mephedrone as a new synthetic amphetamine induces abortion, morphological alterations and mitochondrial dysfunction in mouse embryos
Published in Toxin Reviews, 2021
Ahmad Salimi, Mina Kazemnezhad, Baharak Mohammadzadeh Asl, Farzaneh Jokar, Zhaleh Jamali, Jalal Pourahmad
Mitochondria are essential organelles for ATP generation and their involvement in programed cell death or apoptosis is long proven (Meyer et al.2013). They play main roles in key processes such as synthesis of pyrimidines and steroids; thermogenesis and fever response; heme and iron-sulfur cluster assembly; calcium, copper, and iron homeostasis and calcium signaling (Meyer et al.2013). Mitochondrial toxicity is a key “off-target” effect of many chemicals and toxicant. These agents have now been identified that inhibit mitochondrial transport pathways, uncouple the electron transport chain (ETC), inhibit fatty acid oxidation or uptake, the citric acid cycle, mtDNA replication, and mitochondrial protein synthesis and generation of ROS (Meyer et al.2013). There are several factors that affect mitochondrial vulnerability to foreign toxicants such as accumulation of toxicant in mitochondria, the presence of cytochrome P450s in mitochondria and undefended mitochondrial DNA (mtDNA) (Shaughnessy et al.2014). Some developmental stages are likely more sensitive to mitochondrial toxicants due to age-dependent differences in mitochondrial content, mitochondrial metabolism, and mitochondrial defense/repair mechanisms (Thundathil et al.2005). Our histopathological studies showed that mephedrone induced damages in liver, brain and placenta. Our studies on isolated mitochondria obtained from brain, liver and placenta confirmed that maternal consumption of mephedrone causes a significant effect on mitochondrial toxicity parameters such as ROS formation, MMP collapse, mitochondrial swelling in placenta and brain of mouse fetus.
Manganese dioxide nanosheets induce mitochondrial toxicity in fish gill epithelial cells
Published in Nanotoxicology, 2021
Cynthia L. Browning, Allen Green, Evan P. Gray, Robert Hurt, Agnes B. Kane
MnO2 nanosheets induced mitochondrial dysfunction and cytotoxicity after prolonged exposures of 48 and 72 h, respectively. These delayed responses suggest that cellular uptake and intracellular dissolution are early steps leading to MnO2 nanosheet toxicity. This is the first study to demonstrate that 2D MnO2 nanosheets induce mitochondrial dysfunction. The mitochondrial toxicity observed occurred at sub-cytotoxic levels, suggesting it is not a result of mitochondrial damage that occurs during apoptosis or necrosis.