Mitochondrial administration alleviates lead- and cadmium-induced toxicity in rat renal cells.

The role of heavy metals such as lead (Pb) and cadmium (Cd) in the etiology of many diseases has been proven. Also, these heavy metals can affect the normal mitochondrial function. Mitochondrial administration therapy is one of the methods used by researchers to help improve mitochondrial defects and diseases. The use of isolated mitochondria as a therapeutic approach has been investigated in in vivo and in vitro studies. Accordingly, in this study, the effects of mitochondrial administration on the improvement of toxicity caused by Pb and Cd in renal proximal tubular cells (RPTC) have been investigated. The results showed that treatment to Pb and Cd caused an increase in the level of free radicals, lipid peroxidation (LPO) content, mitochondrial and lysosomal membrane damage, and also a decrease in the reduced glutathione content in RPTC. In addition, reports have shown an increase in oxidized glutathione content and changes in energy (ATP) levels. Following, the results have shown the protective role of mitochondrial administration in improving the toxicity caused by Pb and Cd in RPTC. Furthermore, the mitochondrial internalization into RPT cells is mediated through actin-dependent endocytosis. So, it could be suggested that the treatment of Pb- and Cd-induced cytotoxicity in RPTC could be carried out through mitochondria administration.

Toxicity of superparamagnetic iron oxide nanoparticles on retinoblastoma mitochondria.

PURPOSE: Retinoblastoma (RB) is one of the most important cancers in children with a higher rate of prevalence in developing countries. Despite different approaches to the treatment of RB, it seems necessary to discover a new approach to its treatment. Today, mitochondria are recognised as an important target in the treatment of cancer. Superparamagnetic iron oxide nanoparticles (SPIONs) have been studied by researchers due to their important biological effects. METHODS: In this study, the effects of SPIONs on mitochondria isolated from Y79 retinoblastoma cells were investigated. RESULTS: The results showed that SPIONs were able to increase the reactive oxygen species (ROS) level and subsequently damage the mitochondrial membrane and release cytochrome c a as one of the important pro-apoptotic proteins of RB mitochondria. Furthermore, the results indicated a decrease in cell viability and an increase in caspase-3 activity in Y79 retinoblastoma cells. CONCLUSIONS: These events can lead to the killing of cancerous mitochondria. Our results suggest that SPIONs can cause mitochondrial dysfunction and death in RB mitochondria.

Mitochondrial transplantation attenuates toxicity in rat renal proximal tubular cells caused by Favipiravir.

OBJECTIVES: Exogenous mitochondria transplantation or mitotherapy can be used to swap out unhealthy mitochondria for functioning ones. Treatment of mitochondrial diseases using this approach may be beneficial. METHODS: In this study, we looked at the effect of transplanting newly isolated mitochondria on the toxicity that favipiravir (FAV) causes in renal proximal tubular cells (RPTCs). In this study, parameters such as lactate dehydrogenase (LDH) leakiness, reactive oxygen species (ROSs) production, damage to the lysosome membrane, reduced glutathione (GSH) content, extracellular oxidized glutathione (GSSG) content, GSH/GSSG ratio, ATP level, mitochondrial membrane potential (MMP) collapse, Bcl-2 content, and caspase-3 activity were used to assess the protective effects of mitochondrial transplantation against FAV-induced mitochondrial toxicity. KEY FINDINGS: The statistical analysis showed that the cytotoxicity, ROS production, MMP collapse, lysosomal damage, GSSG levels, and caspase-3 activity brought on by FAV in RPTCs were reduced by transplanting the healthy mitochondria. In addition, it led to an increase in ATP level, GSH content, Bcl-2 content, and GSH/GSSG ratio in RPTCs. CONCLUSIONS: A recent study found that mitochondrial transplantation is a powerful therapeutic approach for treating nephrotoxicity brought on by xenobiotics.

Cardiotoxicity of chloroquine and hydroxychloroquine through mitochondrial pathway.

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 < 0.05). Also, the highest effect of these two drugs has been observed in 60 min (p < 0.05). The statistical results showed that compared to CQ, HCQ is able to cause the release of cytochrome c from mitochondria in all applied concentrations (p < 0.05). 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.

Mitochondrial transplantation against gentamicin-induced toxicity on rat renal proximal tubular cells: the higher activity of female rat mitochondria.

Mitochondrial dysfunction is a fundamental mechanism leading to drug nephrotoxicity, such as gentamicin-induced nephrotoxicity. Mitochondrial therapy (mitotherapy) or exogenous mitochondria transplantation is a method that can be used to replace dysfunctional mitochondria with healthy mitochondria. This method can help in the treatment of diseases related to mitochondria. In this research, we studied the transplantation effect of freshly isolated mitochondria on the toxicity induced by gentamicin on renal proximal tubular cells (RPTCs). Furthermore, possible gender-related effects on supplying exogenous rat kidney mitochondria on gentamicin-induced RPTCs were investigated. At first, the normality and proper functioning of fresh mitochondria were assessed by measuring mitochondrial succinate dehydrogenase activity (SDH) and changes in mitochondrial membrane potential (MMP). Then, the protective effects of mitochondrial transplantation against gentamicin-induced mitochondrial toxicity were evaluated through parameters including lactate dehydrogenase (LDH) leakiness, reactive oxygen species (ROS) production, lipid peroxidation (LPO) content, reduced glutathione (GSH) level, extracellular oxidized glutathione (GSSG) level, ATP level, MMP collapse, and caspase-3 activity. According to the statistical analysis, transplanting the healthy mitochondria decreased the cytotoxicity, ROS production, MMP collapse, LPO content, GSSG levels, and caspase-3 activity caused by gentamicin in RPTCs. Also, it has caused an increase in the level of ATP and GSH in the RPTCs. Furthermore, higher preventive effects were observed for the female group. According to the current study, mitochondrial transplantation is a potent therapeutic method in xenobiotic-caused nephrotoxicity.

Mitochondrial Transplantation Therapy against Ifosfamide Induced Toxicity on Rat Renal Proximal Tubular Cells.

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.

Risperidone Toxicity on Human Blood Lymphocytes in Nano molar Concentrations.

Risperidone is an atypical antipsychotic drug used for the pharmacotherapy of psychiatric disorders. Some reports indicate that risperidone is toxic to various systems of the body, including the immune system. This study evaluated the toxicity effect of risperidone on human blood lymphocytes. To achieve this aim, lymphocytes were isolated using Ficoll paque plus. The results showed that risperidone (12, 24 and 48 nM) causes toxicity in human blood lymphocytes by increasing the level of intracellular reactive oxygen species (ROS), damage to lysosomal membrane, the collapse of the mitochondrial membrane potential (MMP), and increased extracellular oxidized glutathione (GSSG). Also, exposure of human blood lymphocytes to risperidone is associated with a decrease in intracellular glutathione (GSH) levels. Finally, it could be concluded that oxidative stress is one of the mechanisms of risperidone-induced toxicity in human blood lymphocytes.

The perchloroethylene-induced toxicity in dry cleaning workers lymphocytes through induction of oxidative stress.

Evaluation of the compounds and metabolites, and studying their side effects in the workplace is essential. This study was designed to evaluate the exposure of dry  cleaning workers to perchloroethylene (PEC), and its liver and kidney damage, and oxidative stress in B-lymphocytes isolated from the workers. Blood samples were evaluated for liver (alanine transaminase [ALT] and aspartate transaminase [AST]) and kidney (BUN and creatinine) markers. For measurement of PEC, exhaled, personal, and ambient air samples were collected and analyzed gas chromatography (GC-FID) through the NIOSH 1003 and 3704 methods. Also, the parameters of oxidative stress including the level of reactive oxygen species (ROS), glutathione (GSH), oxidized glutathione (GSSG), and lipid peroxidation (LPO) in B-lymphocytes were evaluated. The results showed that the levels of liver enzymes ALT and AST in dry cleaning workers are higher than in the control group. The personal exposure levels and exhaled air concentration of PEC in dry cleaning workers were above the recommended national occupational exposure limits (OELs) and the biological exposure index (BEI). The levels of ROS, LPO, and GSSG in B-lymphocytes from the dry cleaning workers are higher than the control group, and the levels of GSH in dry cleaning workers are lower. The results suggested that exposure of dry cleaning workers to PEC could be associated with liver damage and oxidative damage in B-lymphocytes.

Toxicity of Hydrogen Sulfide on Rat Brain Neurons.

Hydrogen sulfide (H2S) is a toxic compound known as a member of the gasotransmitter family. H2S has the ability to inhibit the cytochrome c oxidase enzyme in the mitochondrial respiratory chain. Mitochondria play an important role in energy production and the brain needs energy for normal function. Mitochondrial dysfunction is associated with neurodegenerative diseases. This study investigated the mechanisms of cytotoxicity induced by H2S in brain neurons. thioacetamide has been used to produce H2S in water solutions. The results of the study showed that thioacetamide at concentrations of 116, 232 and 464 µg/ml was able to increase the level of reactive oxygen species (ROS), collapse in mitochondrial membrane potential (MMP), damage to the lysosomal membrane, increase in the level of oxidized glutathione (GSSG) and decrease in the level of reduced glutathione (GSH) in brain neurons. The results of the study suggested that H2S causes damage to mitochondria and lysosomes in brain neurons that could be associated with neurodegenerative diseases.

Selective Toxicity Effect of Chrysaora quinquecirrha Crude Venom on Human Colorectal Tumor Cells by Directly Targeting Mitochondria.

OBJECTIVE: Compounds isolated from marine animals have different pharmacological effects. In this study, we investigated the effects of sea nettle (Chrysaora quinquecirrha) crude venom on human colon cancer mitochondria. METHODS: First, mitochondria were isolated from healthy colon tissue and cancerous colon tissue, and then mitochondrial function (SDH activity), reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP) collapse, mitochondrial swelling, and cytochrome c release were measured. RESULTS: The results showed that crude venom of Chrysaora quinquecirrha (180, 360 and 720 µg/ml) can significantly impair mitochondrial function (**P<0.01 and ***P<0.001) and consequently increase the level of ROS (*P<0.05 and ****P<0.0001), collapse in MMP (*P<0.05 and ****P<0.0001), mitochondrial swelling (**** P<0.0001) and release of cytochrome c (* P<0.05 and *** P<0.001) only in mitochondria isolated from human colon cancer tissue. CONCLUSION: The results concluded that crude venom of Chrysaora quinquecirrha (180, 360 and 720 µg/ml) has no side effects on normal mitochondria and only selectively affects cancerous mitochondria. It seems that after further research, Chrysaora quinquecirrha can be considered as a drug candidate for the treatment of patients with colon cancer.

Cold Atmospheric Plasma Versus Cisplatin Against Oral Squamous Cell Carcinoma: A Mitochondrial Targeting Study.

Plasma therapy and the study of the effects of cold atmospheric plasma (CAP) on tissues and living cells have been considered by scientific researchers in recent years. CAP is used in the treatment of cancer, but its anti-cancer mechanism has not been fully studied. Therefore, we studied the toxicity effect of CAP by using argon as feed gas and the synergistic effects of CAP with cisplatin on tumor cells and mitochondria isolated from tumor legions of the rat model of oral squamous cell carcinoma (OSCC). For this reason, we determined the possible toxic alterations of CAP on mitochondrial upstream events and activation of caspase-3 as the key major downstream event of apoptosis. Also, the effects of cisplatin (10 µM) as a positive control and its synergistic effects with CAP (IC50 concentration) were investigated. The results showed that CAP reduced mitochondrial dysfunction by reduction in succinate dehydrogenase (SDH) activity. Also, CAP in concentrations of 1200, 2400, and 4800 a.u. has been able to increase the level of reactive oxygen species (ROS), mitochondrial swelling, damage to the mitochondrial membrane, cytochrome c release, and activation of the final mediator of apoptosis (caspase-3) only in the OSCC group. CAP at 4800 a.u concentration had similar effects to cisplatin (10 µM). Synergistic effects between CAP (2400 a.u) and cisplatin (10 µM) have also been reported. Based on all results CAP showed positive and promising results on mitochondrial upstream parameters leading to activation of caspase-3, the final mediator of apoptosis only on OSCC cells and mitochondria without any significant effect on normal cells and mitochondria.

Effectiveness of UV/SO32- advanced reduction process for degradation and mineralization of trichlorfon pesticide in water: identification of intermediates and toxicity assessment.

This study aimed to investigate the degradability, mineralization, proposed decomposition pathway, intermediate products, and toxicity of effluent from trichlorfon (TCF) degradation in water by UV/sulfite-advanced reduction process (UV/S-ARP). This study was experimentally performed in a photochemical reactor as a batch operation. The source of light was a UV lamp. Sulfite ion was used as the reducing agent. After the treatment, the residual concentration of TCF was measured by liquid chromatography equipped with tandem mass spectrometry (LC-MS/MS). UV/S-ARP had the highest performance at an initial pH of 7, a sulfite ion concentration of 120 mg/L, a contact time of 60 min, and a TCF concentration of 10 mg/L. Under such conditions, the degradation efficiency of TCF was 96.0%, and the amount of mineralization based on the removal of TOC and COD was 74.6% and 79.5%, respectively. The results of the degradation mechanism showed that eaq- and SO3•- have played the greatest role in dechlorination and transformation of TCF. Based on the identified intermediates, more complex compounds are transformed into compounds with simpler structures by UV/S-ARP. Evaluating the toxicity of TCF by-products via ECOSAR bioassay showed that as-generated intermediates do not have acute and chronic adverse effects on fish. The results of our study indicated that the advanced reduction process could be an effective process for the purification of TCF-contaminated water.

Selective Toxicity Effect of Fatty Acids Omega-3, 6 and 9 Combination on Glioblastoma Neurons through their Mitochondria.

Glioblastoma (GBM) is one of the most common malignant tumors of the central nervous system that occurs in the brain and is a deadly disease. Despite the different approaches to the treatment of this malignancy, the discovery of new compounds with anti-cancer effects seems necessary. In this study, the selective toxicity effects of omega 3, 6 and 9 combinations on mitochondria isolated from U87MG human glioma cells and also human embryonic kidney 293 cells (HEK293) as normal control were investigated. The results indicated that the omega 3, 6 and 9 combinations significantly reduced succinate dehydrogenase (SDH) activity only in mitochondria isolated from U87MG human glioma cells. Additionally, exposure of mitochondria isolated from U87MG human glioma cells to this combination was associated with a selective increase in the level of reactive oxygen species (ROS), the collapse of the mitochondrial membrane potential (MMP), mitochondrial swelling and cytochrome c release. However, these effects were not observed in mitochondria isolated from HEK293 cells (as a normal group). According to results, it is proposed that the combination of omega 3, 6 and 9 could induce toxicity in U87MG human glioma cells through their mitochondria. This combination can be helpful as a complementary therapy in patients with GBM.

Toxicity effect of sesquiterpene lactones from Jurinea gabrieliae bornm on mitochondria isolated from U87 cells.

Sesquiterpene lactones (SLs) are a typical group of secondary metabolites in asteraceae family and well-known for their biologically potential in treatment of various diseases such as cancer and inflammation. Glioblastoma (GBM) is a most common brain malignancy in adults with poor prognosis. Finding phytochemicals with potential targeting mitochondria has been suggested as an important approach for many malignancies. In this study, we purified three guaianolide-type SLs, including 8-deacyloxy-8α-(methylacryloxy)-subluteolide (A), subluteolide (B) and janerin (C) from Jurinea gabrieliae Bornm by chromatography methods. Then, mitochondrial toxicity parameters were evaluated. All three SLs selectively inhibited SDH activity in mitochondria from U87 cells but not mitochondria from normal rat brain. In addition these SLs increased ROS formation and cytochrome c release and MMP collapse only in mitochondria from U87 cells but not normal rat neurons. Our results suggest that all three SLs may act as potential agents for future development in anti-glioma therapy.

Restoration and stabilization of acrylamide-induced DNA, mitochondrial damages and oxidative stress by chrysin in human lymphocyte.

BACKGROUND: Acrylamide (AA) is a water-soluble toxic chemical that is considered one of the most important food contaminants. Furthermore, AA is considered a major public health risk. METHODS: This study was designed to evaluate the effects of AA on cytotoxicity, oxidative damage and genotoxicity in human lymphocytes and also to evaluate the protective effects of the chrysin (CH). Lymphocytes after isolation from the blood were treated with AA (50 µM), AA (50 µM) plus CH (10, 25, 50 µM) and CH (50 µM), and parameters such as cell viability, mitochondrial and lysosomal damage, as well as oxidative damage to DNA were examined. RESULTS: The results showed that CH was able to reduce cytotoxicity, reactive oxygen species (ROS) levels, lipid peroxidation (LPO) level, collapse in mitochondrial membrane potential (MMP) and oxidative damage of DNA caused by AA in human lymphocytes. Also, co-treatment of the AA-exposed human lymphocytes with CH increases the glutathione (GSH) levels. CONCLUSION: Results suggest that CH (10, 25, 50 µM) shows a protective role in AA-induced cytotoxicity, oxidative stress, mitochondrial damage and DNA oxidative damage.

Cytotoxicity Studies of the Crude venom and Fractions of Persian Gulf Snail (Conus textile) on Chronic Lymphocytic Leukemia and Normal Lymphocytes.

BACKGROUND: Marine animals have been considered by many researchers due to their various pharmacological effects. One group of marine animals that have been studied is cone snails. The conotoxin obtained from these marine animals has various therapeutic effects. METHODS: This study was designed to investigate the apoptotic effects of crude venom of Conus textile and its fractions (A and B) on chronic lymphocytic leukemia (CLL) cells. Accordingly, parameters such as cell viability, reactive oxygen species (ROS) level, collapse in mitochondrial membrane potential (MMP), lysosomal membrane damage and caspase-3 activation were evaluated. RESULTS: The results showed that the crude venom (50, 100 and 200 µg/ml) from Conus textile and its fraction B (50, 100 and 200 µg/ml) significantly reduced viability in CLL B-lymphocyte. In addition, exposure of CLL B-lymphocyte to fraction B (50, 100 and 200 µg/ml) was associated with an increase in the level of ROS, the collapse of the MMP, damage to the lysosomal membrane, and activation of caspase-3. CONCLUSION: According to results, it was concluded that fraction B from crude venom of Conus textile causes selective toxicity on CLL B-lymphocyte with almost no effect on a normal lymphocyte. Furthermore, this venom fraction could be a promising candidate for induction of apoptosis in patients with CLL through the mitochondrial pathway.

The selective toxicity of superparamagnetic iron oxide nanoparticles (SPIONs) on oral squamous cell carcinoma (OSCC) by targeting their mitochondria.

In recent years, many researchers have made tremendous efforts into using nanotechnology in biomedical applications and science, such as magnetic resonance imaging, drug delivery, and in particular, oncological therapeutic via superparamagnetic iron oxide nanoparticles (SPIONs). Head and neck squamous cell carcinoma (HNSCC) and especially oral squamous cell carcinoma (OSCC) have been a serious and ongoing concern. There are many strong emphases on the importance of toxic mechanisms due to oxidative stress and specifically, the changed cellular response. Therefore, our study was designed to evaluate the effects of SPIONs on OSCC mitochondria because of the usefulness of the application of these nanoparticles in cancer treatment and diagnosis. An increased level of reactive oxygen species (ROS) is one of the substantial mechanisms found for SPIONs in this study, and initially originated from disruption of the electron transfer chain shown by a decrease in mitochondrial succinate dehydrogenase activity. Increased ROS formation subsequently followed a decline of mitochondrial membrane potential, the release of mitochondrial cytochrome complex, and mitochondrial swelling in the OSCC mitochondria compared with almost no effect in normal mitochondria. In addition, the SPIONs decreased cell viability and increased lipid peroxidation level and caspase-3 activity in OSCC cells. The results represented that the exposure to the SPIONs induced selective toxicity only on the OSCC but not normal mitochondria. Based on our findings, we finally concluded that the SPIONs may be considered as a potential therapeutic candidate for the treatment of OSCC.

Apigenin ameliorates oxidative stress and mitochondrial damage induced by multiwall carbon nanotubes in rat kidney mitochondria.

The toxicity of carbon nanotubes (CNTs) toward the mitochondria of the kidney is not fully recognized and still needs further research. Apigenin (APG) is known as a flavonoid compound and natural antioxidant. The purpose of this study was to assess the ameliorative role of APG against multiwall CNT (MWCNT)-induced kidney toxicity in rats. The animals were administrated with APG (10 mg/kg) for 2 weeks and then were exposed to MWCNTs (5 mg/m3 ) in pure and impure forms (10 and 100 nm) for 5 h/day and 5 days/week. Then, mitochondria were isolated from the kidney tissue and mitochondrial toxicity parameters were measured. Decreases in succinate dehydrogenase activity have been reported in all groups exposed to MWCNTs. Results indicated that MWCNTs in both forms and sizes were able to increase the generation of reactive oxygen species, decline mitochondrial membrane potential, induce mitochondrial swelling, and release cytochrome c in isolated kidney mitochondria. The pretreatment of APG decreased all the abovementioned mitochondrial damage and oxidative stress parameters induced by both pure and impure MWCNTs. Our results showed that MWCNTs have the ability to enter the body, subsequently, cross cellular barriers, and reach the kidney as a sensitive organ, which can result in mitochondrial damage in kidney cells including renal tubular cells. In addition, APG can be an effective nutritional antioxidant regimen against MWCNT-induced kidney damage.

Luteolin attenuates Fipronil-induced neurotoxicity through reduction of the ROS-mediated oxidative stress in rat brain mitochondria.

Luteolin (LUT) as a natural compound found in vegetables and fruits has various pharmacological effects. Fipronil (FPN), as a pesticide, has been considered for its effect on the antioxidant system and induction of oxidative stress. This study was designed to investigate the protective effects of LUT against the oxidative stress and mitochondrial toxicity induced by FPN on the rat brain. Several parameters such as mitochondrial reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP) collapse, mitochondrial swelling, cytochrome c release, mitochondrial glutathione (GSH), lipid peroxidation (LPO) and Adenosine triphosphate (ATP) levels were assessed. Results indicated that the administration of LUT (25 µM) significantly improved oxidative stress and mitochondrial damages induced via FPN (6, 12 and 24 µM) in isolated mitochondria from the brain. These results show that LUT exerted protective effects against FPN-induced neurotoxicity in vitro through improving oxidative stress and mitochondrial damages.

Mitochondrial, lysosomal and DNA damages induced by acrylamide attenuate by ellagic acid in human lymphocyte.

Acrylamide (AA), is an important contaminant formed during food processing under high temperature. Due to its potential neurotoxicity, reproductive toxicity, hepatotoxicity, immunotoxicity, genotoxicity and carcinogenicity effects, this food contaminant has been recognized as a human health concern. Previous studies showed that acrylamide-induced toxicity is associated with active metabolite of acrylamide by cytochrome P450 enzyme, oxidative stress, mitochondrial dysfunction and DNA damage. In the current study, we investigated the role of oxidative stress in acrylamide's genotoxicity and therapeutic potential role of ellagic acid (EA) in human lymphocytes. Human lymphocytes were simultaneously treated with different concentrations of EA (10, 25 and 50 µM) and acrylamide (50 µM) for 4 h at 37°C. After 4 hours of incubation, the toxicity parameters such cytotoxicity, ROS formation, oxidized/reduced glutathione (GSH/GSSG) content, malondialdehyde (MDA) level, lysosomal membrane integrity, mitochondria membrane potential (ΔΨm) collapse and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were analyzed using biochemical and flow cytometry evaluations. It has been found that acrylamide (50 µM) significantly increased cytotoxicity, ROS formation, GSH oxidation, lipid peroxidation, MMP collapse, lysosomal and DNA damage in human lymphocytes. On the other hand, cotreatment with EA (25 and 50 µM) inhibited AA-induced oxidative stress which subsequently led to decreasing of the cytotoxicity, GSH oxidation, lipid peroxidation, MMP collapse, lysosomal and DNA damage. Together, these results suggest that probably the co-exposure of EA with foods containing acrylamide could decrease mitochondrial, lysosomal and DNA damages, and oxidative stress induced by acrylamide in human body.