• Title/Summary/Keyword: Clearance of toxic compounds

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Therapeutic implication of autophagy in neurodegenerative diseases

  • Rahman, Md. Ataur;Rhim, Hyewhon
    • BMB Reports
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    • v.50 no.7
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    • pp.345-354
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    • 2017
  • Autophagy, a catabolic process necessary for the maintenance of intracellular homeostasis, has recently been the focus of numerous human diseases and conditions, such as aging, cancer, development, immunity, longevity, and neurodegeneration. However, the continued presence of autophagy is essential for cell survival and dysfunctional autophagy is thought to speed up the progression of neurodegeneration. The actual molecular mechanism behind the progression of dysfunctional autophagy is not yet fully understood. Emerging evidence suggests that basal autophagy is necessary for the removal of misfolded, aggregated proteins and damaged cellular organelles through lysosomal mediated degradation. Physiologically, neurodegenerative disorders are related to the accumulation of amyloid ${\beta}$ peptide and ${\alpha}-synuclein$ protein aggregation, as seen in patients with Alzheimer's disease and Parkinson's disease, respectively. Even though autophagy could impact several facets of human biology and disease, it generally functions as a clearance for toxic proteins in the brain, which contributes novel insight into the pathophysiological understanding of neurodegenerative disorders. In particular, several studies demonstrate that natural compounds or small molecule autophagy enhancer stimuli are essential in the clearance of amyloid ${\beta}$ and ${\alpha}-synuclein$ deposits. Therefore, this review briefly deliberates on the recent implications of autophagy in neurodegenerative disorder control, and emphasizes the opportunities and potential therapeutic application of applied autophagy.

Antioxidant, Cytotoxicity and Cytoprotective Potential of Extracts of Grewia Flava and Grewia Bicolor Berries

  • Masisi, Kabo;Masamba, Riach;Lashani, Keletso;Li, Chunyang;Kwape, Tebogo E.;Gaobotse, Goabaone
    • Journal of Pharmacopuncture
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    • v.24 no.1
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    • pp.24-31
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    • 2021
  • Objectives: Accumulation of cellular reactive oxygen species (ROS) leads to oxidative stress. Increased production of ROS, such as superoxide anion, or a deficiency in their clearance by antioxidant defences, mediates cellular pathology. Grewia Spp fruits are a source of bioactive compounds and have notable antioxidant activity. Although the antioxidant capacity of Grewia Spp has been studied, there is very limited evidence that links the antioxidant activities of Grewia bicolor and Grewia flava to the inhibition of free radical formation associated with damage in biological systems. Methods: This study evaluated the protective effects of Grewia bicolor and Grewia flava extracts against free radical-induced oxidative stress and the resulting cytotoxicity effect using HeLa cells. Antioxidant properties determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and total phenolic content (TPC) assays showed significantly higher (p < 0.05) antioxidant activity in Grewia flava (ethanol extract) than Grewia flava (water extract) and Grewia bicolor (ethanol and water extracts). Results: Using 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide or MTT assay, cytotoxicity results showed that extracts of Grewia bicolor and Grewia flava were less toxic to HeLa cells at tested concentrations compared to the untreated control. This confirmed the low toxicity of these edible fruits at the tested concentrations in HeLa cells. Furthermore, hydrogen peroxide (H2O2)-induced cell loss was effectively reduced by pre-incubating HeLa cells with Grewia bicolor and Grewia flava extracts, with Grewia flava (ethanol extract) revealing better protection. Conclusion: The effect was speculated to be associated with the higher antioxidant activity of Grewia flava (ethanol extract). Additional studies will warrant confirmation of the mechanism of action of such effects.

Ototoxic Evaluation of Cis-platinum (Cis-Platinum의 이중독증에 관한 임상적 고찰)

  • 홍원표;정명현;오혜경;이경재
    • Proceedings of the KOR-BRONCHOESO Conference
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    • 1982.05a
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    • pp.17.1-17
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    • 1982
  • In 1965, Rosenberg reported that platinum compounds not only inhibit growth and cell division of E. coli but also has anti-tumor activity. Since then, through animal and clinical experiments by Welsch(1971), Speer(1972), Rossof(1972), Hill(1974), and Wittes(1975), it was proved that Cis-platinum has excellent supressive effects on malignant tumor, especially on head and neck cancer. Accordingly, Cis-platinum is now widely used, sometimes without any other durg, or sometimes with Bleomycin and Methotrexate etc. Inspite of the strong anticancer effect, the use of Cis-platinum is quite often discouraged because of the reports that Cis-platinum causes auditory impairment at high frequencies above the speech range due to inner ear damage and irreversible change in the renal tubules. Since Kohonen et al(1965), Standnicki et al(1974) reported that Cisplatinum has toxic effects at the basal turn of the cochlea using guinea pig, many studies on ototoxicity after infusion of Cis-platinum have been carried out using animals. But the studies on ototoxicity in human beings can hardly be found except in reports by Piel et al(1974) and Hong et al (1979). So the authors did a study which tried to clarify the ototoxic effect by comparing the hearing level after infusion of Cis-plastinum with the hearing level before infusion of Cis-plastinum in 30 patients who was treated with Cis-platinum and admitted to the dept. of otolaryngology of Yonsei University Hospital during 2 years and a half from July. 1979 to March. 1982 and the following results were obtained. 1) The results of auditory evaluation, using the pure tone average, hearing loss of 4kHz and 8kHz, Speech Reception Threshold, PB score, SISI showed that the difference of dosage does not change the hearing level after infusion of Cis-platinum and before infusion of Cis-platinum. 2) Cis-platinum had no effect on the hearing level of patients with conductive hearing loss, or with sensorineural hearing loss, as well as with normal hearing level. 3) The infusion of Cis-platinum did not cause any change in creatinine clearance, creatinine, uric acid, but only one case showed that Cis-platinum caused severe nephrotoxicity. 4) The infusion of Cis-plastinum did not cause any change in hemoglobin, leukocyte count, platelet count and there was no correlation with the amount of infusion. 5) To see the side effect of hydration practiced with the infusion of Cis-platinum, the electrolytes, particularly the K level in the serum was measured. But the results did not show any change. 6) Judging from the results of this study mentioned above, ototoxicity caused by infusion of Cis-platinum can be prevented by sufficient hydration. Also the results might say that the appropriate method of infusion of Cis-platinum might be effective in the patients with head and neck cancer who had sensorineural hearing loss for whom the infusion of Cis-platinum has been absolutely cotraindicated.

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