Evaluation of the protective effects of berberine and berberine nanoparticle on insulin secretion and oxidative stress induced by carbon nanotubes in isolated mice islets of langerhans: an in vitro study.

The increasing use of single-walled carbon nanotubes (SWCNT) in various fields highlights the need to investigate the test toxicity of these nanoparticles in humans. Previous documents showed that SWCNT induced oxidative stress. Oxidative stress and reactive oxygen species (ROS) cause cell dysfunction and reduced insulin secretion. Therefore, this study aimed to investigate the effects of SWCNT on oxidative stress and insulin secretion of islets also evaluate the protective effects of berberine (BBR) and berberine nanoparticles (NP-BBR) as antioxidants on pancreatic ß-islets. Double emulsion with solvent evaporation was the technique used to prepare nanoparticles in this study. Islets were isolated and pretreated with various concentrations of BBR and NP-BBR and then treated with single dose of SWCNT (160 µg). The results of this study showed that SWCNT decreased cell viability based on MTT assay, reduced insulin secretion of islets, increased malondialdehyde (MDA) amounts, reactive oxygen species (ROS) levels, reduced glutathione (GSH) levels, catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities, whereas pretreatment of islets with low doses of BBR (5 and 15 µM) and NP-BBR (5 µM) significantly reversed all changes induced by SWCNT. These findings suggested that SWCNT might trigger other pathways involved in insulin secretion by activating the oxidative stress pathway in the pancreatic islets, reducing insulin secretion, consequently diabetes. BBR and NP-BBR as antioxidants were able to protect pancreatic ß-islets and prevent the progression of diabetes.

Nephrotoxicity of Albendazole and Albendazole Loaded Solid Lipid Nanoparticles in Mice with Experimental Hydatidosis.

Purpose: Cystic echinococcosis (CE) is a serious contemporary public health problem. Different CE treatment methods are of considerable importance, with albendazole (ABZ) being one of the most preferred drugs for CE treatment and prophylaxis. In this study, we evaluated the nephrotoxicity caused by ABZ and ABZ-loaded solid lipid nanoparticles (SLNs) in mice with experimental hydatid cyst. Methods: ABZ-loaded SLNs were produced by micro-emulsification and a high shear homogenization technique. Thereafter, we evaluated the physicochemical characterization of the product. Live protoscolices were injected into mice to induce experimental hydatidosis. Mice were then treated with ABZ and ABZ-loaded SLNs. The nephrotoxicity effects were evaluated by biochemical and histopathological surveys. Results: Significantly different blood urea nitrogen (BUN) levels were observed between the two infected groups (ABZ treatment and ABZ-loaded SLN treatment) and the control group. The kidney malondialdehyde (MDA) and glutathione (GSH) levels of the infected groups were not significantly different from those of the control group. The histopathological study revealed nephropathic and pathologic changes in the ABZ and ABZ-loaded SLN groups. Conclusion: ABZ formulated for ABZ-loaded SLNs had a more prominent chemoprophylactic efficacy on CE and fewer side effects than ABZ alone. Neither ABZ nor ABZ-loaded SLNs caused significant biochemical and histopathological defects on the kidney, and all functional biochemical markers stayed within the normal range. Therefore, ABZ-loaded SLNs could be a potential new product for CE treatment.

Gallic Acid and Gallic Acid Nanoparticle Modulate Insulin Secretion Pancreatic ß-Islets against Silica Nanoparticle-Induced Oxidative Damage.

Due to the increasing use of silica nanoparticles (SiNPs), their possible toxic effects on human health have undoubtedly been considered. Previous studies proved that SiNPs induced oxidative stress. Reactive oxygen species (ROS) and oxidative stress disrupt cell function and decrease insulin secretion. Therefore, this study intended to assess the effects of SiNPs on oxidative stress and insulin secretion and also the protective effects of gallic acid (GA) and gallic acid nanoparticles (NP-GA) on pancreatic ß-islets. In this study, the mice islets were separated and pretreated with various concentrations of GA and NP-GA then treated with a single dose of SiNPs. The cell viability of islets examined by MTT assay and also the levels of ROS, malondialdehyde (MDA), glutathione (GSH); activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and insulin secretion were evaluated. The results of MTT assay showed that SiNPs reduced islet viability in a dose-dependent manner and also insulin secretion, induced the formation of ROS, augmented MDA amounts, and decreased GSH levels, SOD, GPx, and CAT activities. Furthermore, pretreatment of islets with GA and NP-GA significantly returned these alterations at low dose. These findings suggested that SiNPs induced oxidative stress in the pancreatic islets, which could be one of the reasons for the decrease in insulin secretion and inducing diabetes. This study also showed that low doses of GA and NP-GA boosted the antioxidant defense system in the pancreatic ß-islets, preventing oxidative stress and, consequently, the progression of diabetes.

Pretreatment with Gallic Acid Mitigates Cyclophosphamide Induced Inflammation and Oxidative Stress in Mice.

BACKGROUND: Cyclophosphamide (CP) as an alkylating compound has been widely applied to treat cancer and autoimmune diseases. CP is observed to be nephrotoxic in humans and animals because it produces reactive oxygen species. Gallic Acid (GA), a polyhydroxy phenolic compound, is reported to exhibit antioxidant and anti-inflammatory effects. OBJECTIVE: The current research aimed at evaluating the GA effect on CP-related renal toxicity. METHODS: In total, 35 male mice were assigned to 5 groups. Group1: receiving normal saline, group 2: CP group, receiving one CP injection (200 mg/kg; i.p.) on day 6. Groups 3 and 4: GA+CP, GA (10 and 30 mg/kg; p.o.; respectively) received through six consecutive days plus CP on the 6th day 2 hr after the last dose of GA, group 5: received GA (30 mg/kg; p.o.) for six consecutive days. Then on day 7, blood samples were collected for determining Creatinine (Cr), serum kidney injury molecule-1 (KIM-1), Blood Urea Nitrogen (BUN), and Neutrophil Gelatinase-Associated Lipocalin (NGAL) concentrations. Malondialdehyde (MDA), Nitric Oxide (NO) concentration, Catalase (CAT), Superoxide Dismutase (SOD), Glutathione (GSH), Glutathione Peroxidase (GPx) activities, and IL-1ß, TNF-α levels were assessed in renal tissue. RESULTS: CP administration significantly increases KIM-1, NGAL, Cr, BUN, MDA, NO, IL-1ß, and TNF-α level. It also decreases GSH concentration, SOD, GPx, and CAT function. Pretreatment with GA prevented these changes. Histopathological assessments approved the GA protective effect. CONCLUSION: Our results showed that GA is possibly effective as a protective agent in cyclophosphamide- associated toxicities.

Berberine ameliorates testosterone-induced benign prostate hyperplasia in rats.

INTRODUCTION: Benign prostatic hyperplasia (BPH) is a major urologic problem that mostly develops in older males. Oxidative stress and inflammation influence the occurrence of BPH. Berberine (BBR) is a natural ingredient that has antioxidant and anti-inflammatory properties. The current research aims at examining the effects of BBR on testosterone-stimulated BPH in rats. METHODS: Animals were randomly categorized to six groups. In the control group, normal saline and olive oil were injected as the vehicle. BPH group: received testosterone (3 mg/kg, subcutaneous, 28 days), BPH + BBR groups; received BBR (25 and 50 mg/kg, p.o, 28 days), BPH + finasteride groups: received finasteride (1 mg/kg, p.o, 28 days), BBR (50 mg/kg, p.o, alone) was administered for subjects in the BBR group. On the 29th day, after anesthesia, cervical dislocation was used to kill the subjects. Serum concentration of testosterone and dihydrotestosterone was measured and prostate tissues were excised and used for biochemical, inflammation, and histological analysis. RESULTS: BBR prevented increased serum concentrations of testosterone and dihydrotestosterone. BBR considerably reduced BPH-stimulated oxidative stress and inflammation through preventing the rise in lipid peroxidation and nitrite concentration and declined the accumulations of pro-inflammatory cytokines (e.g. interleukin 1ß and tumor necrosis factor α) and declining the depletion rate of GSH and the function of catalase and superoxide dismutase. Histopathological investigations reported that administration of BBR could suppress testosterone-stimulated BPH. CONCLUSION: This study demonstrated that BBR could significantly prevent the development of BPH in rats.

Epicatechin ameliorative effects on methotrexate-induced hepatotoxicity in mice.

BACKGROUND: Due to the fact that methotrexate is widely used both as an immunosuppressive drug and as a chemotherapy agent, many studies are needed to reduce the side effects of this drug on non-target organs. PURPOSE: This study was designed to investigate the effects of epicatechin (Epi) on MTX (methotrexate)-induced hepatotoxicity in mice. RESEARCH DESIGN: After 1 week for adaptation, we randomly divided 42 male Naval Medical Research Institute mice into six groups: (I) control; (II) Epi (100 mg/kg, po); (III) MTX (20 mg/kg, i.p.) on the fifth day; and (IV, V, and VI) Epi (25, 50, and 100 mg/kg, po) + MTX (20 mg/kg, i.p.) on the fifth day. At day 10, the mice were sacrificed and serum factors, oxidative stress markers, and inflammatory cytokines were measured. RESULTS: MTX increased activity level of serum enzymes (alanine aminotransferase and aspartate aminotransferase), lipid peroxidation marker (malondialdehyde), and inflammatory factors including interleukin-1 beta, tumor necrosis factor-alpha, and nitric oxide. Furthermore, MTX decreased glutathione level and activity level of catalase, superoxide dismutase, and glutathione peroxidase. Epi was able to reduce the destructive effects of oxidative/antioxidant system imbalance and inflammatory reactions and also histopathological damage in MTX intoxicated mice. Epi pretreatment reduced liver dysfunction by improving the antioxidant defense system, anti-inflammatory effects, and alleviation of histopathological damage in MTX hepatotoxicity. CONCLUSIONS: Accordingly, Epi can be used as a therapeutic agent in hepatotoxicity associated with MTX chemotherapy.

Dimethyl fumarate reduces oxidative stress, inflammation and fat deposition by modulation of Nrf2, SREBP-1c and NF-κB signaling in HFD fed mice.

Nonalcoholic fatty liver disease (NAFLD) occurs due to lipid metabolic disorders, which is associated with hepatic oxidative stress and inflammation. There is no definitive drug treatment for this disease. Accordingly, the present study aimed to evaluate the effects of dimethyl fumarate (DMF) as one of the superior effective drugs that induces a transcription factor of nuclear factor erythroid 2-related factor 2 (Nrf2) on development of NAFLD in mice. The metabolic disturbance in High-fat diet (HFD)-treated animals was associated with hyperlipidemia, increased activity levels of hepatic enzymes in serum, hyperglycemia, hyperinsulinemia, oxidative stress and inflammation. DMF supplementation had anti-inflammatory, antioxidant, anti-lipogenic and molecular compatibility effects induced by HFD in mice. In comparison to the HFD group, the DMF therapy could significantly suppress the sterol regulatory element binding protein-1 c (SREBP-1c) gene and protein levels, as well as upregulate the Nrf2 gene and protein levels. Additionally, the anti-inflammatory activity was observed for the DMF by inhibiting the nuclear factor kappa B (NF-κB) level. DMF reduces the development of NAFLD induced by HFD in mice through the modulation of transcription factors Nrf2, SREBP-1c and NF-κB. Thus, DMF can be considered as an effective candidate in the treatment of human NAFLD.

Taurine attenuates valproic acid-induced hepatotoxicity via modulation of RIPK1/RIPK3/MLKL-mediated necroptosis signaling in mice.

Valproic acid (VPA) is known as a common drug in seizure and bipolar disorders treatment. Hepatotoxicity is the most important complication of VPA. Taurine (Tau), an amino acid, has antioxidant effects. The present research was conducted to evaluate the protective mechanisms of Tau on VPA-induced liver injury, especially focusing on the necroptosis signaling pathway. The sixty-four male NMRI mice were divided into eight groups with eight animals per each. The experiment groups pretreated with Tau (250, 500, 1000 mg/kg) and necrostatine-1 (Nec-1, 1.8 mg/kg) and then VPA (500 mg/kg) was administered for 14 consecutive days. The extent of VPA-induced hepatotoxicity was confirmed by elevated ALP (alkaline phosphatase), AST (aspartate aminotransferase), ALT (alanine aminotransferase) levels, and histological changes as steatosis, accumulation of erythrocytes, and inflammation. Additionally, VPA significantly induced oxidative stress in the hepatic tissue by increasing ROS (reactive oxygen species) production and lipid peroxidation level along with decreasing GSH (glutathione). Hepatic TNF-α (tumor necrosis factor) level, mRNA and protein expression of RIPK1 (receptor-interacting protein kinase 1), RIPK3, and MLKL (mixed lineage kinase domain-like pseudokinase) were upregulated. Also, the phosphorylation of MLKL and RIPK3 increased in the VPA group. Tau could effectively reverse these events. Our data suggest which necroptosis has a key role in the toxicity of VPA through TNF-α-mediated RIPK1/RIPK3/MLKL signaling and oxidative stress. Our findings suggest that Tau protects the liver tissue against VPA toxicity via inhibiting necroptosis signaling pathway mediated by RIPK1/RIPK3/MLKL and suppressing oxidative stress, and apoptosis.

An ultra-sensitive optical aptasensor based on gold nanoparticles/poly vinyl alcohol hydrogel as acceptor/emitter pair for fluorometric detection of digoxin with on/off/on strategy.

A novel nanobiosensor was prepared by aptamer and gold nanoparticles conjugate in poly vinyl alcohol hydrogel for sensitive detection of digoxin in human plasma samples. The developed nanobiosensor was characterized by Fourier transform infrared spectroscopy, transmission electron microscopy, and dynamic light scattering instrument. In this sensor the hydrogel acted as a fluorescent probe. The fluorescence intensity of the hydrogel was quenched by aptamer stabilized gold nanoparticles as energy acceptor. Upon addition of digoxin, the aptamer/drug complex was formed and the fluorescence of the hydrogel was restored because of destabilization and aggregation of gold nanoparticles in the presence of salt. The affecting parameters on the nanobiosensor performance were assessed and under the optimized conditions the external and in plasma calibration curves were linear in the 10-1000 ng L-1 digoxin concentration range with detection limits of 2.9 and 3.1 ng L-1, respectively. The relative standard deviations for 5 replicate determinations of 50, 250, and 500 ng L-1 of digoxin, were 7.3, 5.1, and 3.8%, respectively. This nanofluoroprobe was successfully applied for determination of digoxin in spiked plasma samples without any pretreatment procedure.

A novel strategy for detection of small molecules based on aptamer/gold nanoparticles/graphitic carbon nitride nanosheets as fluorescent biosensor.

Herein, a novel ultrasensitive strategy has been developed by designing a label free fluorescent nano-aptasensor for monitoring of small moecules in human plasma. In this nano-aptasensor, graphitic carbon nitride nanosheets were used as fluorescent probe. The fluorescence intensity of the probe was decreased by interaction between graphitic carbon nitride nanosheets and label-free aptamer/gold nanoparticles conjugate, via Fluorescence resonance energy transfer mechanism. Upon addition of the analyte, the fluorescence of graphitic carbon nitride nanosheets was restored due to the aptamer/analyte interaction, and the aggregation of gold nanoparticles in the presence of salt. The influence of various factors on sensing method was investigated, and under the approved conditions, the fluorescence signal showed a linear relation with Digoxin concentration in the range of 10-500 ng L-1 with limit of detection down to 3.2 ng L-1 relative standard deviations for 25, 100 and 500 ng L-1 of analyte concentrations were 2.6, 4.0 and 6.5%, respectively. This strategy provided a simple, rapid, cost effective and reproducible experimental model, with successful application for determination of Digoxin in plasma samples without any pretreatment steps.

Alleviation of Liver Dysfunction, Oxidative Stress and Inflammation Underlies the Protective Effect of Ferulic Acid in Methotrexate-Induced Hepatotoxicity.

INTRODUCTION: In multiple studies, involvement of oxidative stress in the pathogenesis of methotrexate (MTX)-mediated liver damage has been confirmed. Use of many drugs has been examined experimentally in order to prevent or diminish oxidative stress. However, no study has yet examined the effects of ferulic acid (FA) on MTX-induced liver damage. This study aimed at evaluating the effects of FA on protection against liver damage induced by MTX in mice. MATERIALS AND METHODS: In this the mice were divided into five groups in a random manner: I) control; II) MTX (20 mg/kg); III and IV) FA (50 and 100 mg/kg) + MTX; and V) FA (100 mg/kg), and we measured serum factors, oxidative stress and inflammatory factors. RESULTS: In the MTX group, accumulation of inflammatory cells, accumulation of red blood cell (RBC), and nuclear pyknosis (NP) were detected in the liver. In line with the histological data, the levels of nitric oxide (NO), malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-α increased (TNF-α), whereas the reduced glutathione (GSH), catalase (CAT), total antioxidant capacity (TAC), superoxide dismutase (SOD), and glutathione peroxidase (GPx) content reduced in the MTX group. However, FA ameliorated these hazardous effects in the antioxidant and anti-inflammatory systems in MTX-treated groups. CONCLUSION: Based on our findings, oxidative stress impairment and MTX-induced liver damage were ameliorated following FA pretreatment at both histological and biochemical levels. Therefore, FA can be effectively used in abrogation of MTX-induced toxicity.

Subcellular Organelle Toxicity Caused by Arsenic Nanoparticles in Isolated Rat Hepatocytes.

BACKGROUND: Arsenic, an environmental pollutant, is a carcinogenic metalloid and also an anticancer agent. OBJECTIVE: To evaluate the toxicity of arsenic nanoparticles in rat hepatocytes. METHODS: Freshly isolated rat hepatocytes were exposed to 0, 20, 40, and 100 µM of arsenic nanoparticles and its bulk counterpart. Their viability, reactive oxygen species level, glutathione depletion, mitochondrial and lysosomal damage, and apoptosis were evaluated. RESULTS: By all concentrations, lysosomal damage and apoptosis were clearly evident in hepatocytes exposed to arsenic nanoparticles. Evaluation of mitochondria and lysosomes revealed that lysosomes were highly damaged. CONCLUSION: Exposure to arsenic nanoparticles causes apoptosis and organelle impairment. The nanoparticles have potentially higher toxicity than the bulk arsenic. Lysosomes are highly affected. It seems that, instead of mitochondria, lysosomes are the first target organelles involved in the toxicity induced by arsenic nanoparticles.

Ellagic Acid Prevents Oxidative Stress, Inflammation, and Histopathological Alterations in Acrylamide-Induced Hepatotoxicity in Wistar Rats.

The present study was designed to investigate the changes in rat liver tissue after administration of acrylamide (ACR) and ellagic acid (EA). The latter compound was applied for its strong antioxidant and anti-inflammatory properties. In the present study, 35 male Wistar rats were randomly divided into five equal groups. These groups were normal saline (NS), ACR (20 mg/kg), ACR + EA (10 and 30 mg/kg EA), and EA (30 mg/kg). At the end of the experiment, the rats were decapitated. Biochemical and histopathological studies were conducted on liver and serum samples. ACR administration significantly decreased hepatic GSH level, SOD, GPx, and CAT activity when compared to the NS group. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), nitric oxide (NO), protein carbonyl (PC), malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1ß) levels increased as a result of ACR administration. Administration of EA (more potently at a dose of 30 mg/kg) resulted in a significant reversal of biochemical, inflammatory, and hepatic markers in ACR-intoxicated rats. These biochemical and inflammatory disturbances were supported by histopathological observations of the liver. Our results indicate that EA might be useful for the treatment of the hepatotoxicity induced by ACR via ameliorative effects on biochemical, oxidative stress, and inflammatory indices.

Antifungal effect of the effect of Securigera securidaca L. vaginal gel on Candida species.

BACKGROUND AND PURPOSE: Candida species are opportunistic fungi, capable of causing acute and chronic infections in the gastrointestinal tract, vagina, and oral mucosa, among which Candida albicans is the most important species. The Securigera securidaca L. is used as an antiseptic to treat some diseases in traditional Iranian medicine. The aim of this study was to evaluate the antimicrobial activity of S. securidaca extracts and vaginal gel against different Candida species. MATERIALS AND METHODS: Antifungal effects of different extracts and vaginal gel of S. securidaca were investigated against Candida species. By using well diffusion test, different concentrations of the collected S. securidaca extracts and vaginal gel were examined to test their antifungal activity against C. albicans, C. parapsilosis, and C. krusei. RESULTS: The ethanol extract and vaginal gel with the ethanol extract of S. securidaca showed the most anti-fungal activity against all three strains. CONCLUSION: The S. securidaca extract had a significant inhibitory effect on the different species of Candida; however, the highest inhibitory effect was found against C. albicans. In order to treat candidiasis, more research is required to check the efficacy of this plant in this domain.

Microarray analysis of apoptosis gene expression in liver injury induced by chronic exposure to arsenic and high-fat diet in male mice.

Rapid growth in the incidence of liver disease is largely attributable to lifestyle and environmental contaminants, which are often overlooked as the leading causes of this problem. Thus, the possible contribution of arsenic (As) to high-fat diet (HFD)-induced liver damage was examined via microarray analysis. To perform this experiment, a total number of 40 healthy adult male NMRI mice (22-30 g) were used. To this end, these animals were randomly assigned to four groups of 10. Oxidative stress and histopathological parameters were also evaluated in the liver of the mice exposed to a minimally cytotoxic concentration of As (50 ppm) in drinking water while being fed with a HFD for 20 weeks. Subsequently, apoptosis gene expression profiling was utilized via real-time (RT) PCR array analysis. The results showed that As had increased the amount of HFD-induced liver damage and consequently amplified changes in oxidative stress factors, histopathological parameters, as well as apoptosis pathway genes. Investigating the expression profile of apoptosis pathway genes similarly revealed that caspase-8, as a main upstream contributor to the apoptosis pathway, might play an important role in the induction of apoptosis generated by As and HFD. Ultimately, this study highlighted that As in drinking water could increase sensitivity in mice to HFD-induced liver disease through strengthening apoptosis pathway.

Single-walled and multiwalled carbon nanotubes induce oxidative stress in isolated rat brain mitochondria.

Single-walled carbon nanotubes (SWCNTs) and multiwalled carbon nanotubes (MWCNTs) are broadly applicable across a variety of industrial fields. Despite their usefulness in many different applications, oxidative stress-induced toxicity of SWCNTs and MWCNTs has not been widely investigated. The present study examined the effects of SWCNTs and MWCNTs on rat brain mitochondria using the 3,4 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and indices of reactive oxygen species (ROS), based on measurements of malondialdehyde (MDA), glutathione (GSH), and mitochondrial membrane potential. Based on the MTT assay, exposure to SWCNTs and MWCNTs decreased mitochondrial survival and viability in a dose-dependent manner. Findings also indicated that MWCNTs and SWCNTs could damage mitochondrial membranes and induce the formation of ROS, as indicated by increased levels of MDA and decreased GSH content. The results of this study suggest that SWCNTs and MWCNTs likely damage brain tissue mitochondria by increasing oxidative stress and possibly activating the apoptosis pathway as well as other pathways of cytotoxicity.

The hepatoprotective effect of livergol microemulsion preparation (nanoparticle) against bromobenzene induced toxicity in mice.

Livergol (LG), which is the extract of Silybum marianum and commonly known as milk thistle possess hepatoprotective effect and have got licensed for sale in Iran and other countries. LG was evaluated for its capacity to counteract the toxic effects of bromobenzene (BB) on mouse liver. The bioactive component of this plant is known to reinforce naturally occurring liver function through antioxidant activity, the stimulation of bile production and regeneration by the liver organ, resulting in enhanced protection against toxicants, hepatitis, and cirrhosis. The major bioactive components of this product are the flavonolignan ssilibinin, silidianin, silicristin, and isosilibinin. Mice were treated for 10 days with daily gavage of microemulsions (MEs), into which 0-400 mg/kg LG was dispersed. 0.36 ml/kg BB was injected intraperitoneally (ip) to each animal on day 10, followed by sacrifice on day 11, and histological evaluation of hematoxylin-eosin (HE)-stained liver tissue samples, afterwards followed by evaluation liver enzymes level, aminotransferase (AST), alanine aminotransaminase (ALT) and alkaline phosphatase (ALP) activities. Significant suppression of BB-mediated damage to liver tissue, and increased in AST, ALT, and ALP level was observed to occur dose-responsively with LG administration, suggesting a use for LG as a chemoprotectant for persons chronically exposed to industrial solvents.

Crocin ameliorates methotrexate-induced liver injury via inhibition of oxidative stress and inflammation in rats.

BACKGROUND: Methotrexate (MTX) is used commonly in the treatment of various cancers and inflammatory diseases; nevertheless, the associated hepatotoxicity has limited its clinical application. Crocin (CRO) is described as a natural carotenoid with analgesic, antioxidant, and antiinflammatory properties. This study aimed to determine the effects of CRO on MTX-induced hepatotoxicity. METHODS: For pretreatment, CRO at doses of 25 and 50 mg/kg (po), as well as 20 mg/kg (ip) of MTX, was injected in rats. RESULTS: MTX led to hepatotoxicity, as confirmed by the significant increase in liver markers, histopathological changes, decreased GSH content, and reduced antioxidant enzyme activity (i.e., CAT, SOD, and GPx). It increased TNF-α, IL-1ß, lipid peroxidation, and nitric oxide levels. Nevertheless, by increasing antioxidant defense in hepatic tissues and reducing oxidative stress and proinflammatory mediators, pretreatment with CRO could alleviate hepatotoxicity. CONCLUSION: CRO can inhibit MTX-induced hepatotoxicity through improving antioxidant defense and reducing oxidative stress and inflammation.

Neuroprotective effects of Ellagic acid against acrylamide-induced neurotoxicity in rats.

Acrylamide (ACR) is an environmental contaminant and a well-known neurotoxin. Ellagic acid (EA), a natural plant polyphenol, has shown a variety of beneficial effects. The present study was designed to explore whether EA could attenuate ACR-induced neurotoxicity in rats and to explore the underlying mechanisms. Animals were divided into five groups. Group 1 was treated with normal saline (2 mL/kg) for 30 days. Group 2 was treated with ACR (20 mg/kg, orally) for 30 days. Groups 3 and 4 were treated with ACR and EA (10 and 30 mg/kg, orally) for 30 days. Group 5 was treated with EA (30 mg/kg, orally) for 30 days. Open field, rotarod and passive avoidance test were conducted to evaluate behavioral changes, respectively. The brain cortex was used for histological examination. Different oxidative parameters and inflammatory biomarkers were assessed in the brain cortex. ACR-administered rats showed a considerable impairment in exploratory behavior, motor performance as well as cognition. Our data also showed that ACR administration significantly increases malondialdehyde, nitric oxide, interleukin-1ß and tumor necrosis factor-α levels. Moreover, it decreases brain glutathione level, superoxide dismutase, glutathione peroxidase, catalase activity. Co-administration of EA (especially 30 mg/kg, p.o.) prevented these changes; however, it did not affect the glutathione peroxidase activity. These results were supported by histopathological observations of the brain. Our results suggest that EA can be useful for protecting brain tissue against ACR-induced neurotoxicity through ameliorative effects on inflammatory indices and oxidative stress parameters.

Protective effect of inulin on methotrexate- induced liver toxicity in mice.

Methotrexate (MTX) is an effectively used drug in the treatment of cancer and inflammatory diseases but, its use is related with hepatotoxicity. Inulin with antioxidant properties has hepatoprotective effects. In this research, we assessed inulin effects on MTX-induced liver toxicity. 48 male mice were randomly assigned into 6 equal groups. Mice were Pre-treatment with inulin (100, 200 and 400 mg/kg) for 9 consecutive days, orally) and MTX (10 mg/kg, intraperitoneally) was received on the 7th, to 9th day. Blood and liver were collected to assess liver functional test in serum samples and Stress oxidative biomarkers, pathological changes, the expressions levels of apoptotic factors, such as, Bcl-2, caspase -3 and miR-122 in the mice liver. The results indicated that MTX administration induced marked liver damage and serums factors of all of the mice. Furthermore, there was a decrease in the Bcl2 and an increase in the caspase-3 activity and miR-122 expression compared to the control group. Instead, inulin Pre-treatment clearly improved these variations induced by MTX. Finally, our results revealed the new evidence that the hepatoprotective effects of inulin might be mediated via the modulations of apoptotic and oxidative stress factors.