Search

Melanoma is known as an aggressive and highly lethal cancer. The poor prognosis and resistance to treatment are characteristics of melanoma. In melanoma cells, apoptosis signaling which relies heavily on the acute activity of mitochondria and reactive oxygen species (ROS) formation is suppressed. Studies have shown that compounds isolated from marine herbs and animals, have been shown to have cytotoxic consequences on cancerous cells in prior research. This study was designed to evaluate the apoptotic effect of methanolic extract of Persian Gulf shell-less marine mollusc (Peronia peronii) on skin mitochondria isolated from animal model of melanoma.Melanoma mitochondria obtained from skin of melanoma animal model are studied in this research to see whether extracts from Persian Gulf shell-less marine molluscIn this study, the mitochondria were isolated from melanoma cells via differential centrifugation were treated with various concentrations (650, 1300 and 2600 µg/ml) of methanolic extract of Peronia peronii. Then MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) viability assay, Reactive oxygen species (ROS) determination, Mitochondrial Membrane Potential (MMP) decline assay, mitochondrial swelling and cytochrome c release determination were performed. Flow cytometry assay of % apoptotic vs necrotic phenotypes was also performed on extract treated melanoma cells.The results of MTT assay showed that different concentrations ofBased on these results, the presence of potentially bioactive compounds in

Mitochondrial dysfunction is a basic mechanism leading to drug nephrotoxicity. Replacement of defective mitochondria with freshly isolated mitochondria is potentially a comprehensive tool to inhibit cytotoxicity induced by ifosfamide on renal proximal tubular cells (RPTCs). We hypothesize that the direct exposure of freshly isolated mitochondria into RPTCs affected by ifosfamide might restore mitochondrial function and reduce cytotoxicity. So, the aim of this study was to assess the protective effect of freshly isolated mitochondrial transplantation against ifosfamide-induced cytotoxicity in RPTCs. Therefore, the suspension of rat RPTCs (106 cells/ml) in Earle’s solution with the pH of 7.4 at 37°C was incubated for 2 h after ifosfamide (4 mM) addition. Fresh mitochondria were isolated from the rat kidney and diluted to the needed concentrations at 4°C. The media containing suspended RPTCs was replaced with mitochondrial-supplemented media, which was exposed to cells for 4 hours in flasks-rotating in a water bath at 37°C. Statistical analysis demonstrated that mitochondrial administration reduced cytotoxicity, lipid peroxidation (LPO), reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP) collapse, lysosomal membrane damage, extracellular oxidized glutathione (GSSG) level, and caspase-3 activity induced by ifosfamide in rat RPTCs. Moreover, mitochondrial transplantation increased the intracellular reduced glutathione (GSH) level in RPTCs affected by ifosfamide. According to the current study, mitochondrial transplantation is a promising therapeutic method in xenobiotic-caused nephrotoxicity pending successful complementary in vivo and clinical studies.

Background Medical therapies can cause cardiotoxicity. Chloroquine (QC) and hydroxychloroquine (HQC) are drugs used in the treatment of malaria and skin and rheumatic disorders. These drugs were considered to help treatment of coronavirus disease (COVID-19) in 2019. Despite the low cost and availability of QC and HQC, reports indicate that this class of drugs can cause cardiotoxicity. The mechanism of this event is not well known, but evidence shows that QC and HQC can cause cardiotoxicity by affecting mitochondria and lysosomes. Methods Therefore, our study was designed to investigate the effects of QC and HQC on heart mitochondria. In order to achieve this aim, mitochondrial function, reactive oxygen species (ROS) level, mitochondrial membrane disruption, and cytochrome c release in heart mitochondria were evaluated. Statistical significance was determined using the one-way and two-way analysis of variance (ANOVA) followed by post hoc Tukey to evaluate mitochondrial succinate dehydrogenase (SDH) activity and cytochrome c release, and Bonferroni test to evaluate the ROS level, mitochondrial membrane potential (MMP) collapse, and mitochondrial swelling. Results Based on ANOVA analysis (one-way), the results of mitochondrial SDH activity showed that the IC50 concentration for CQ is 20 µM and for HCQ is 50 µM. Based on two-way ANOVA analysis, the highest effect of CQ and HCQ on the generation of ROS, collapse in the MMP, and mitochondrial swelling were observed at 40 µM and 100 µM concentrations, respectively (p Conclusions The results suggest that QC and HQC can cause cardiotoxicity which can lead to heart disorders through oxidative stress and disfunction of heart mitochondria.

Aims: Alzheimer is a multifactorial disease that is caused by several different etiopathogenic mechanisms. The aim of this study is to evaluate the protective effects of Allium jesdianum extract on cognitive dysfunction, mitochondrial/cellular, and genetic parameters in Streptozotocin-induced Alzheimer's disease (AD) Rat Model. Main methods: A single dose of STZ (3 mg/kg, i.c.v.) was injected to male Wistar rats in order to establish a model of sporadic AD. A. jesdianum extract (100,200, 400 mg/kg/day) and donepezil (5 mg/kg/day) were administered through oral gavage as treatment for 14 days after model induction. Cognitive function (radial arm water maze test), mitochondrial toxicity parameters consisting succinate dehydrogenase (SDH) activity, mitochondrial ROS formation, MMP decline, mitochondrial swelling and efflux of cytochrome c in various parts of the rat brain (whole brain, frontal cortex, hippocampus and cerebellum), and miR-330, miR-132, Bax and Bcl-2 genes expression in isolated rat brain neurons through RT-qPCR analysis were evaluated. Key findings: A.jesdianum extract significantly attenuated i.c.v-STZ-induced cognitive dysfunction and mitochondrial upstream toxic events. As a result of STZ injection, Bax gene was highly expressed, whereas miR-330, miR-132 and Bcl-2 gene were poorly expressed and A. jesdianumreverses the expression of the above miRNAs and genes in favor of improving AD and reducing neuronal apoptosis. Significance: A. jesdianum showed the neuroprotective capability against oxidative stress and cognitive impairment induced by STZ in rats shows its helpful therapeutic worth in AD.

Lead (Pb) is a highly toxic heavy metal. Pb exposure could adversely affect many organs, including the male reproductive system. Oxidative stress and mitochondrial impairment play a fundamental role in the pathogenesis of Pb-induced male reproductive system injury. Taurine (TAU) is abundantly found in mammalian bodies. The positive effects of TAU on oxidative stress biomarkers and mitochondrial function have been reported. The current study evaluated the effects of TAU on Pb-induced reproductive toxicity. Mice received Pb (20 mg/kg/day; gavage, 35 consecutive days). Then, sperm indices (quality and quantity) together with sperm kinetics, sperm mitochondrial parameters, testicular and sperm oxidative stress biomarkers, testis and plasma testosterone levels, and the expression of genes involved in the steroidogenesis process have been evaluated. Pb caused significant histopathological alterations and oxidative stress in male mice's reproductive system and sperm. Moreover, significant mitochondrial function impairment was evident in sperm isolated from Pb-treated mice. Pb exposure also suppressed the expression of StAR, 17β-HSD, CYP11A, and 3β-HSD genes in the male gonad. It was found that TAU (500 and 1000 mg/kg) significantly improved oxidative stress biomarkers in both male gonads and gametes of Pb-treated mice. TAU also significantly restored sperm mitochondrial function and kinetics. The expression of genes involved in steroidogenesis was also higher in TAU-treated animals. These data suggest TAU as an effective agent against Pb-induced reproductive toxicity. The effects of TAU on oxidative stress markers, mitochondrial function, and the steroidogenesis process seem to play a fundamental role in its protective properties. Further studies are warranted to detect the precise protective effects of this amino acid in the reproductive system. Lead (Pb) is a toxic element that adversely affects the male reproductive system. Mitochondrial impairment and oxidative stress have a crucial role in the Pb-induced reproductive toxicity. Taurine (TAU) could considerably improve the reproductive toxicity induced by Pb via enhancing mitochondrial function and mitigating oxidative stress indices. ΔΨ, mitochondrial membrane potential; ATP, adenosine triphosphate.

Depleted uranium (DU) is an important by product in uranium enrichment process. Due to its applications in civilian and also military activity, DU emerged as environmental pollutant. The exposure to DU can occur via external or internal pathways. In external exposure, mainly beta radiation from the decay products contributes to DU toxicity. Internal exposure to DU is more important and can occur through ingestion of DU-contaminated water and food and inhalation of DU aerosols. There is limited information about health effects and mechanism of DU after environmental exposure. Kidney is reported as the main target organ for the chemical toxicity of this metal that was reported in Persian Gulf syndrome. Alterations in behavior, some neurologic adverse effects, immunotoxicity, embryo-toxicity and hepatotoxicity were observed in chronic exposure to DU. Also, the increased risk of cancer was revealed in epidemiological and experimental studies. Several mechanisms were suggested for DU toxicity such as oxidative stress, mitochondrial toxicity and inflammation. In fact, uranium like other toxic heavy metals can induce oxidative damage and apoptosis via mitochondrial pathway and inflammatory response. In this review, we have discussed the kinetic of DU including source and exposure pathway. In addition, the health effects of DU and also its toxic mechanism have been highlighted.