Therapeutic effects of genistein in experimentally induced ulcerative colitis in rats via affecting mitochondrial biogenesis.

Ulcerative colitis (UC) is an inflammatory bowel disease that affects the mucosa of the colon, resulting in severe inflammation and ulcers. Genistein is a polyphenolic isoflavone present in several vegetables, such as soybeans and fava beans. Therefore, we conducted the following study to determine the therapeutic effects of genistein on UC in rats by influencing antioxidant activity and mitochondrial biogenesis and the subsequent effects on the apoptotic pathway. UC was induced in rats by single intracolonic administration of 2 ml of 4% acetic acid. Then, UC rats were treated with 25-mg/kg genistein. Colon samples were obtained to assess the gene and protein expression of nuclear factor erythroid 2-related factor-2 (Nrf2), heme oxygenase-1 (HO-1), peroxisome proliferator-activated receptor-gamma coactivator (PGC-1), mitochondrial transcription factor A (TFAM), B-cell lymphoma 2 (BCL2), BCL2-associated X (BAX), caspase-3, caspase-8, and caspase-9. In addition, colon sections were stained with hematoxylin/eosin to investigate the cell structure. The microimages of UC rats revealed inflammatory cell infiltration, hemorrhage, and the destruction of intestinal glands, and these effects were improved by treatment with genistein. Finally, treatment with genistein significantly increased the expression of PGC-1, TFAM, Nrf2, HO-1, and BCL2 and reduced the expression of BAX, caspase-3, caspase-8, and caspase-9. In conclusion, genistein exerted therapeutic effects against UC in rats. This therapeutic activity involved enhancing antioxidant activity and increasing mitochondrial biogenesis, which reduced cell apoptosis.

Curative effects of crocin in ulcerative colitis via modulating apoptosis and inflammation.

Ulcerative colitis (UC) is an inflammatory bowel disease with characteristic inflammation to mucosal cells in rectum and colon leading to lesions in mucosa and submucosa. Moreover, crocin is a carotenoid compound among active constituents of saffron with many pharmacological effects as antioxidant, anti-inflammatory and anticancer activities. Therefore, we aimed to investigate therapeutic effects of crocin against UC through affecting the inflammatory and apoptotic pathways. For induction of UC in rats, intracolonic 2 ml of 4% acetic acid was used. After induction of UC, part of rats was treated with 20 mg/kg crocin. cAMP was measured using ELISA. Moreover, we measured gene and protein expression of B-cell lymphoma 2 (BCL2), BCL2-associated X (BAX), caspase-3/8/9, NF-κB, tumor necrosis factor (TNF)-α and IL-1ß/4/6/10. Colon sections were stained with hematoxylin-eosin and Alcian blue or immune-stained with anti-TNF-α antibodies. Microscopic images of colon sections in UC group revealed destruction of intestinal glands associated with infiltration of inflammatory cell and severe hemorrhage. While images stained with Alcian blue showed damaged and almost absent intestinal glands. Crocin treatment ameliorated morphological changes. Finally, crocin significantly reduced expression levels of BAX, caspase-3/8/9, NF-κB, TNF-α, IL-1ß and IL-6, associated with increased levels of cAMP and expression of BCL2, IL-4 and IL-10. In conclusion, protective of action of crocin in UC is proved by restoration of normal weight and length of colon as well as improvement of morphological structure of colon cells. The mechanism of action of crocin in UC is indicated by activation of anti-apoptotic and anti-inflammatory effects.

WRH-2412 alleviates the progression of hepatocellular carcinoma through regulation of TGF-ß/ß-catenin/α-SMA pathway.

Hepatocellular carcinoma is considered one of the most lethal cancers, which is characterised by increasing prevalence associated with high level of invasion and metastasis. The novel synthetic pyrazolo[3,4-b]pyridine compound, WRH-2412, was reported to exhibit in vitro antitumor activity. This study was conducted to evaluate the antitumor activity of WRH-2412 in HCC induced in rats through affecting the TGF-ß/ß-catenin/α-SMA pathway. Antitumor activity of WRH-2412 was evaluated by calculating the rat's survival rate and by assessment of serum α-fetoprotein. Protein expression of TGF-ß, ß-catenin, E-cadherin, fascin and gene expression of SMAD4 and α-SMA were determined in hepatic tissue of rats. WRH-2412 produced antitumor activity by significantly increasing the rats' survival rate and decreasing serum α-fetoprotein. WRH-2412 significantly reduced an HCC-induced increase in hepatic TGF-ß, ß-catenin, SMAD4, fascin and α-SMA expression. In addition, WRH-2412 significantly increased hepatic E-cadherin expression.

Administration of Melatonin in Diabetic Retinopathy Is Effective and Improves the Efficacy of Mesenchymal Stem Cell Treatment.

Stem cell transplantation is a promising therapeutic technique for the treatment of a variety of diseases; nevertheless, stem cell therapy may not always work as well as it could. The goal of this study was to test the hypothesis that employing a powerful antioxidant like melatonin improves stem cell transplantation success and potentiates stem cell function in the therapy of diabetic retinopathy. For this purpose, 50 adult male rats were divided into the following: control group: this group received 0.5 ml of 0.1 M of sodium citrate buffer (pH = 4.5) (intraperitoneal (I.P.)). The confirmed diabetic rats were divided into 4 groups: diabetic group: confirmed diabetic rats received no treatments with a regular follow of the blood glucose profile for 8 weeks; melatonin group: confirmed diabetic rats received melatonin (5 mg/kg/day); stem cell group: the confirmed diabetic rats were given intravitreal injection of stem cells (2 µl cell suspension of stem cells (3 × 104 cells/µl)); and melatonin+stem cell group: confirmed diabetic rats received melatonin (5 mg/kg/day), orally once daily for 8 weeks, and 2 µl cell suspension of stem cells (3 × 104 cells/µl) was carefully injected into the vitreous cavity. Our results showed that administration of melatonin and/or stem cell restored the retinal oxidative/antioxidant redox and reduced retinal inflammatory mediators. Coadministration of melatonin and stem cells enhanced the number of transplanted stem cells in the retinal tissue and significantly reduced retinal BDEF, VEGF, APOA1, and RBP4 levels as compared to melatonin and/or stem alone. We may conclude that rats treated with melatonin and stem cells had their retinal oxidative/antioxidant redox values restored to normal and their histological abnormalities reduced. These findings support the hypothesis that interactions with the BDEF, VEGF, APOA1, and RBP4 signaling pathways are responsible for these effects.

Galaxaura elongata Extract (GE) Modulates Vanadyl Sulfate-Induced Renal Damage via Regulating TGF-ß/Smads and Nrf2/NF-κB Pathways.

Nephrotoxicity becomes a provoked problem as the kidneys are the target of many chemotherapies. For this reason, we aimed to study the protective effect of Galaxaura elongata extract (GE) against the vanadyl sulfate (Van) induced nephrotoxicity in rats. Forty Wistar albino rats (male) were divided into four groups (n = 10) as follows: control group: rats received 0.5% carboxymethyl cellulose (CMC). Galaxa group: rats received GE at a dose (100 mg/kg orally) daily for 6 weeks. Van group: rats injected with Van at a dose (50 mg/kg i.p.) once weekly for 6 successive weeks. Galaxa + Van group: rats received GE at a dose (100 mg/kg orally) daily for 6 weeks concurrently with Van at a dose (50 mg/kg i.p.) for 6 weeks. Our results showed that Van significantly raised urea and creatinine serum levels as compared to the control group as well as disordered renal oxidative/antioxidant redox. Administration of GE with Van alleviated the adverse impact of Van over the kidney tissues. Furthermore, GE administration in Galaxa + Van group downregulates angiotensin-converting enzyme (ACE1) mRNA expression, angiotensin II (Ang II) concentration, transforming growth factor ß (TGF-ß) mRNA expression and protein concentration and Nuclear factor κB (NF-κB) mRNA expression as compared to Van group. Also, GE administration caused a noticeable upregulation of Nrf2 and heme oxygenase-1 (HO-1) expressions with a consequent decrease of DNA fragmentation % compared to Van group. The results of the current study show that simultaneous treatment with GE can alleviate nephrotoxicity caused by Van in diabetic rats. The GE treatment of the Van treated animals restored altered renal oxidative/antioxidant redox values towards normal and lessened fibrosis. These results are consistent with these effects being caused by interactions with the TGF-B/Smads and Nrf2/NF-κB signaling pathways.

Involvement of Mfn2, Bcl2/Bax signaling and mitochondrial viability in the potential protective effect of Royal jelly against mitochondria-mediated ovarian apoptosis by cisplatin in rats.

OBJECTIVES: The current study aimed to assess cisplatin-mediated ovarian apoptosis in a rat model by Royal jelly (RJ). MATERIALS AND METHODS: Thirty female adult albino rats (180-200 g) were divided into three groups (n=10): saline (0.9% NaCl, IP) was given to the control group, the cisplatin group: received (5 mg/kg/once a week IP) for 5 successive weeks, the RJ+Cis. group: received RJ (100 mg/kg/ day PO daily), and Cisplatin (5 mg/kg/once per week IP) for 5 successive weeks. At the end of the experiment, rats were sacrificed and their ovaries were isolated and used for biochemical analysis, molecular investigations and morphometric assessment as well as histological study. Moreover, blood samples were collected for determination of follicle-stimulating hormone (FSH), luteinizing hormone (LH), Estradiol, progesterone and anti-mullerian hormone (AMH). RESULTS: The current study clarified that RJ given to rats prior to cisplatin significantly increased the ovarian and uterine weights, in addition to follicular count at P˂0.05 compared to rats injected only with cisplatin. Moreover, it restored normal ovarian histological structure with a concurrent reduction in FSH, and LH levels, and increased AMH and ovarian hormone concentrations at P˂0.05 compared to cisplatin group. Also, RJ decreased the ovarian antioxidant/oxidative imbalance harmonized with significant suppression of inducible nitric oxide synthase and increase of quinone oxidoreductase 1 mRNA expression at P˂0.05 compared to cisplatin group. CONCLUSION: We concluded that RJ could alleviate mitochondrial-induced ovarian apoptosis caused by cisplatin via increasing anti-apoptotic Bcl2, and diminishing pro-apoptotic Bax with a concomitant increase of Mfn2 mRNA and protein expressions.

Protective effects of hesperidin against MTX-induced hepatotoxicity in male albino rats.

Hesperidin (HD), a bioflavonoid, has been shown to exert hepatoprotective effects. Our aim is to investigate the possible protective effects of HD against methotrexate (MTX) hepatotoxicity in adult male Sprague-Dawley (SD) rats that were divided into four groups (10 rats/each) and were exposed to MTX with or without HD co-administration for consecutive 28 days. The results showed that HD significantly ameliorated MTX-induced increase in liver enzymes and histopathological changes. Hepatic oxidative stress was suppressed by HD, as evidenced by the decrease in malondialdehyde (MDA), with a concomitant increase in total antioxidant activity (TAC), catalase (CAT), and glutathione (GSH) levels. Moreover, co-administration of HD with MTX remarkably upregulated the expression of Nrf2 and HO-1 compared with the MTX group. By the decrease in nuclear factor-kB (NF-κB) pathway and tumor necrosis factor α (TNF-α), HD obviously attenuated inflammatory response in MTX-lesioned livers. Likewise, the downregulation of P53 by HD could explain its antiapoptotic effects as indicated by increase BCl2 and the significant decrease of caspase-9 mRNA expression as compared with the MTX group. Thus, these findings revealed the hepatoprotective nature of HD against MTX hepatotoxicity by attenuating the pro-inflammatory and apoptotic mediators and improving antioxidant aptitude.

Prospective Protective Effect of Ellagic Acid as a SIRT1 Activator in Iron Oxide Nanoparticle-Induced Renal Damage in Rats.

Despite the wide application of iron oxide nanoparticles (IONPs), little is known about the specific mechanism of their nephrotoxic effect. We aimed to evaluate the nephrotoxic effects of iron oxide nanoparticles (IONPs) in vivo and the protective effect of ellagic acid (EA) as a silent information regulator sirtuin 1 (SIRT1) activator against the induced nephrotoxicity. Forty male albino Wistar rats were randomly distributed into four equal groups (10 rats each): the control group (oral saline for 30 days), ellagic acid (EA) group (10 mg/kg b.w. EA, orally for 30 days), IONP group (20 mg/kg b.w. IONP I/P injection at the 24th-30th day), and EA + IONP group (10 mg/kg b.w./day EA for 30 days + 20 mg/kg b.w. IONPs at the 24th-30th day). In the present study, the potent antioxidant and antiapoptotic effects of EA were indicated by the significant overexpression of SIRT1 in renal tissues that leads to significant decreases in renal MDA content, P53 protein level and forkhead-box transcription factor1 (FOXO1) expression, and significant increases in renal GSH level, catalase activity, growth arrest and DNA damage-inducible protein 45 alpha (GADDα45), and renal inhibition of apoptosis protein (KIAP) gene expression levels in the EA + IONP-treated group. These results were confirmed by the improved histopathological renal features with EA administration. In conclusion, the present study provides the first evidence for the usefulness of EA as a sirtuin1 activator in the prevention or treatment of renal damage. Thus, EA could be used as a promising therapy for the prevention of IONP-induced nephrotoxicity.

Correction to: Moringa seed extract alleviates titanium oxide nanoparticles (TiO2-NPs)-induced cerebral oxidative damage, and increases cerebral mitochondrial viability.

The original publication of this paper contains a mistake. The correct title is shown in this paper.

Moringa seed extract alleviates titanium oxide nanoparticles (TiO2-NPs)-induced cerebral oxidative damage, and increases cerebral mitochondrial viability.

To investigate the influence of Moringa seed extract (MSE) on the cerebral Nrf2/NQO1 signaling in TiO2-NPs-induced brain damage, 80 male albino rats were divided into four groups (n = 20); group I was used as a control, group II received TiO2-NPs (500 mg/kg b.w/day orally) for 14 days, group III received MSE (100 mg/kg b.w/day orally) for 30 days, and group IV received MSE an hour before TiO2-NPs administration with the same doses as before. Administration of TiO2-NPs was started on the 17th day for both groups (II) and (IV). Administration of MSE significantly increased the cerebral mitochondrial viability and Nrf2 level with a simultaneous increase of NQO1 mRNA expression. This designates a powerful antioxidant effect of MSE which is indicated by a significant reduction of INOS expression, MDA, TOS, OSI levels, and DNA fragmentation % with a significant increase of GSH concentration, SOD activities, and TAC. MSE possesses an anti-inflammatory effect by a significant reduction of IL-1ß and TNF-α levels, and anti-apoptotic effect manifested by a significant reduction of caspase-3 and Fas levels. In harmonization, dopamine, serotonin concentrations, and acetylcholinesterase activities return back to normal as compared to control group. These results were confirmed by the histopathological features which were alleviated with MSE administration. In conclusion, Nrf2 plays a pivotal role in the mechanism of TiO2-NPs cerebral toxicity and MSE as a Nrf2 activator can provide a powerful cerebroprotective effect, whereas MSE increased the Nrf2 expression and consequently restore the antioxidant activity of brain cells by increasing NQO1 gene expression and cerebral mitochondrial viability as well as inhibition of pro-inflammatory and apoptotic mediators.

Ginger extract ameliorates bisphenol A (BPA)-induced disruption in thyroid hormones synthesis and metabolism: Involvement of Nrf-2/HO-1 pathway.

Environmental exposure to BPA is alarming because of the potential health threats for example those concerning the thyroid glands which may show signs of oxidative stress. This original study aimed to investigate the possible antioxidant protective effects of ginger extract (GE) against BPA-induced thyroid injury in male rats, focusing on its effect on Nrf-2/HO-1 signaling and thyroid hormone synthesis regulating genes. The cascade of events in thyroid injury induced by chronic exposure to BPA (200 mg/kg b.w/day for 35 days) involved a preliminary overproduction of ROS followed by significant (p ≤ 0.05) depletion of reduced glutathione (GSH) levels and superoxide dismutase (SOD) activity as well as significant increases of malondialdehyde (MDA) contents, myeloperoxidase (MPO) activity and inducible nitric oxide synthase (iNOS) gene expression. These actions consequently down-regulate the Nrf-2/HO-I signaling which eventually resulting in the DNA fragmentation within the thyroid tissues. Moreover, BPA administration caused a reduction of thyroid iodide uptake evidenced by significant inhibitions (p ≤ 0.05) of sodium-iodide symporter (NIS), thyroid peroxidase (TPO) and thyroid-stimulating hormone receptor (TSHR) mRNA expressions within the thyroid glands. A subsequent significant decreased serum levels of T3 and T4 accompanied by a significantly increased serum TSH level were also detected. These findings were confirmed by the severe pathological changes detected in the thyroid tissue of BPA treated rats. These biochemical and histological alterations were significantly alleviated with ginger administration (250 mg/kg b.w/day for 35 days) plus BPA. In conclusion, ginger extract is a potent antioxidant that can effectively protect against BPA-induced thyroid oxidative damage by activating the Nrf-2/HO-1 gene expressions and enhancing the thyroid hormones synthesis. This is the first study to show the contribution of Nrf-2/HO-1 pathway to the protective effect of ginger extract against BPA-induced thyroid oxidative damage and thyroid hormonal disruption.

Mechanism of diethylhexylphthalate (DEHP) induced testicular damage and of grape seed extract-induced protection in the rat.

The aim of this study was to determine the effect of diethylhexylphthalate (DEHP) on testicular mitochondrial viability and lipid peroxidation as a possible novel mechanism of PEHP testicular toxicity and whether grape seed extract (GSE) beneficially influences the mitochondrial function in testes of rats exposed to diethylhexylphthalate (DEHP). Sixty male albino rats were divided into three groups (n = 20): group I: was used as a control, group II: received diethylhexylphthalate (DEHP) (500 mg/kg/day orally) alone for 30 days, and group III: received the same DEHP dose in combination with GSE (proanthocyanidins) (100 mg/kg body weight). DEHP administration significantly decreases the testicular mitochondrial viability, mRNA expression of androgen receptors (AR), testosterone hormone concentration, increases mRNA expression of INOS and as compared to control group. It also decreases reduced glutathione (GSH) concentration, glutathione reductase (GR), super oxide dismutase (SOD), Catalase activities and increases lipid peroxidation (LPO) and DNA fragmentation%. In synchronization, a substantial decrease of testicular & epididymal weight and volume which accompanied by considerable alteration of semen character. Grape seed extract (GSE) alleviates the toxic effects of DEHP by increasing the mitochondrial viability, decreases the lipid peroxidation, and increases the testicular antioxidant activity. Our results were confirmed by histopathological and immunhistochemical studies.

Possible Therapeutic Effect of Stem Cell in Atherosclerosis in Albino Rats. A Histological and Immunohistochemical Study.

BACKGROUND: Atherosclerosis is the leading cause of death worldwide. there are no effective approaches to regressing atherosclerosis due to not fully understood mechanisms. Recently, stem cell-based therapies have held promises to various diseases, including vascular diseases. AIM: The present study aimed at investigating the possible effect of cord blood mesenchymal stem cell (MSC) therapy on atherosclerosis. MATERIAL AND METHODS: Eighty adult male albino rats were divided into control group (I), atherogenic group (II): subjected to high cholesterol fed diet (200~300 mg/kg body weight) for 12 weeks and 1.8 million units of vitamin D / kg of diet for 6 weeks. Stem cell therapy group (III): injected with stem cells in the tail vein following confirmation of atherosclerosis. Histological, Immunohistochemical and morphometric studies were performed were conducted. RESULTS: Atherogenic group (II) showed increased aortic thickness, intimal proliferation, smooth muscle proliferation and migration. Increased area % of collagen fibers, iNOS and vimentin immunoreactions were recorded and proved morphometrically. All findings regressed on stem cell therapy. CONCLUSION: A definite therapeutic effect of mesenchymal stem cells was found on atherosclerosis.

The effect of aspirin nanoemulsion on TNFα and iNOS in gastric tissue in comparison with conventional aspirin.

BACKGROUND: No dose of aspirin is free of bleeding risk. Even at a dose as low as 75 mg/day, the risk of upper gastrointestinal bleeding is twice as high as among nonusers. Nanoemulsions (NEs) are emulsion systems with droplet size in nanometer scale in which oil or water droplets are finely dispersed in the opposite phase with the help of a suitable surfactant to stabilize the system. OBJECTIVES: The objective of this study was to determine the effect of aspirin NE in comparison to conventional aspirin. MATERIALS AND METHODS: A total of 24 male rats were used in the study and arbitrarily assigned to four groups. Group 1 was the control group, and was given saline. Group 2 was given blank NE 1.5 mL/kg orally. Group 3 was given aspirin 30 mg/kg body weight orally. Group 4 was given aspirin NE 30 mg/kg body weight orally. Rats were killed, and gastric tissue was quickly excised after dissection of the animals. The tissues were divided into three pieces. The first one was kept in formalin 10% for pathological investigation. The second piece was kept in liquid nitrogen for molecular investigation. The third piece was homogenized in ten volumes of ice-cold phosphate-buffered saline (pH 7) using a Teflon homogenizer until a uniform suspension was obtained. The homogenate was centrifuged at 4,000 rpm for 30 minutes at 4°C to separate the supernatant from cellular debris. The supernatant was then used for the estimation of biochemical assays. RESULTS: The present study shows that aspirin has a toxic effect on the stomach as a result of inducing marked oxidative damage and the release of reactive oxygen species. This was shown by the significant increase in TNFα, iNOS, prostaglandin E2, and malondialdehyde levels, and also a significant decrease in glutathione, glutathione reductase, glutathione peroxidase, catalase, and superoxide dismutase. In the aspirin-treated group compared to the control group, the NE had a protective effect on the stomach and caused less injury than aspirin, indicated by significant decreases in TNFα, iNOS, prostaglandin E2, and malondialdehyde levels, and also significant increases in glutathione, glutathione reductase, glutathione peroxidase, catalase, and superoxide dismutase. The biochemical results were confirmed by histopathological studies. CONCLUSION: Aspirin nanoemulsion has less toxic effect on the gastric mucosa compared to ordinary aspirin. This can be indicated by the increase of the antioxidant activity and the decrease of the inflammatory mediators in the gastric tissue.

Cerium oxide nanoparticles alleviate oxidative stress and decreases Nrf-2/HO-1 in D-GALN/LPS induced hepatotoxicity.

Translocation of the master regulator of antioxidant-response element-driven antioxidant gene, nuclear factor erythroid 2 (Nrf-2) from the cytoplasm into the nucleus and triggering the transcription of hemoxygenase-1 (HO-1) to counteract the oxidative stress is a key feature in D-galactoseamine and lipopolysaccharide (D-GALN/LPS) induced hepatotoxicity. We mainly aimed to study the effect of cerium oxide (CeO2) nanoparticles on Nrf-2/HO-1 pathway whereas; it has previously shown to have an antioxidant effect in liver models. Administration of CeO2 nanoparticles significantly decreased the translocation of the cytoplasmic Nrf-2 with a concomitant decrement in the gene expression of HO-1 as it reveals a powerful antioxidative effect as indicated by the significant increase in the levels of glutathione (GSH), glutathione peroxidase (GPX1), glutathione reductase (GR), superoxide dismutase (SOD) and catalase. In synchronization, a substantial decrement in the levels of inducible nitric oxide synthase (iNOS), TBARS and percentage of DNA fragmentation was established. These results were confirmed by histopathology examination which showed a severe degeneration, haemorrhages, widened sinusoids and focal leukocyte infiltration in D-GALN/LPS treatment and these features were alleviated with CeO2 administration. In conclusion, CeO2 is a potential antioxidant that can effectively decrease the translocation of the cytoplasmic Nrf-2 into the nucleus and decrease HO-1 in D-GALN/LPS induced hepatotoxicity.

Oxidative hepatotoxicity effects of monocrotaline and its amelioration by lipoic acid, S-adenosyl methionine and vitamin E.

Liver is the major site for several xenobiotics metabolism, and formation of toxic metabolites that may be hepatotoxic, therefore the burden of metabolism and exposure to dangerous chemicals make liver vulnerable to a variety of disorders. Our work aimed to investigate the effects of some antioxidants such as lipoic acid (LA), S-adenosyl methionine (SAM) and vitamin E in a trail to investigate the possibility of using these substances to relieve and protect liver from exposure to monocrotaline (MCT). Twenty-five mature adult rats were classified into five groups (five rats in each group), control group, MCT-induced hepatic damage, LA+MCT, SAM+MCT and vitamin E+MCT group. Homogenates of liver samples were used for measuring the oxidative biomarkers and hepatic antioxidant status. The results showed that administration of vitamin E, SAM and LA caused a significant increase in liver glutathione contents, glutathione reductase, glutathione peroxidase and glutathione-S-transferase activities and a significant decrease in hepatic catalase and superoxide dismutase. We could conclude that administration of natural LA, SAM and vitamin E before and after MCT injection modulate the hepatic oxidative stresses induced by MCT in various extents.

The prospective protective effect of selenium nanoparticles against chromium-induced oxidative and cellular damage in rat thyroid.

BACKGROUND: Nanotechnology has enabled researchers to synthesize nanosize particles that possess increased surface areas. Compared to conventional microparticles, it has resulted in increased interactions with biological targets. OBJECTIVE: The objective of this study was to determine the protective ability of selenium nanoparticles against hexavalent chromium-induced thyrotoxicity. DESIGN: Twenty male rats were used in the study, and arbitrarily assigned to four groups. Group 1 was the control group, and was given phosphate-buffered saline. Group 2 was the chromium-treated group and was given K2Cr2O7 60 µg/kg body weight intraperitoneally as a single dose on the third day of administration. Group 3 was the nano-selenium-treated group and was given selenium nanoparticles (size 3-20 nm) 0.5 mg/kg body weight intraperitoneally daily for 5 consecutive days. Group 4 was the nano-selenium chromium-treated group, which received selenium nanoparticles for 5 days and a single dose of K2Cr2O7 on the third day of administration. MATERIALS AND METHODS: Blood samples were collected from rats for measuring thyroid hormones (free triiodothyronine [T3] and free thyroxine [T4]) and oxidative and antioxidant parameters (malondialdehyde [MDA], reduced glutathione [GSH], catalase, and superoxide dismutase [SOD]). Upon dissection, thyroid glands were taken for histopathological examination by using paraffin preparations stained with hematoxylin and eosin (H&E) and Masson's trichrome. Immunohistochemical staining was performed for detecting cellular proliferation using Ki67 antibodies. RESULTS: The present study shows that K2Cr2O7 has a toxic effect on the thyroid gland as a result of inducing a marked oxidative damage and release of reactive oxygen species. This was shown by the significant decrease in free T3 and T4 and GSH levels, which was accompanied by significant increases in catalase, SOD, and MDA in the chromium-treated group compared to the control group. Se nanoparticles have a protective effect on K2Cr2O7-induced thyroid damage, as a result of correcting the free T3 and T4 levels and GSH, catalase, SOD, and MDA compared to the K2Cr2O7-treated group. Administration of nano-selenium alone in the nano-selenium-treated group had no toxic effect on rats' thyroid compared to the control group. The biochemical results were confirmed by histopathological, immunohistochemical and pathomorphological studies.

Deltamethrin-induced oxidative stress and biochemical changes in tissues and blood of catfish (Clarias gariepinus): antioxidant defense and role of alpha-tocopherol.

BACKGROUND: The pyrethroid class of insecticides, including deltamethrin, is being used as substitutes for organochlorines and organophosphates in pest-control programs because of their low environmental persistence and toxicity. This study was aimed to investigate the impact of commonly used pesticides (deltamethrin) on the blood and tissue oxidative stress level in catfish (Clarias gariepinus); in addition to the protective effect of α-tocopherol on deltamethrin induced oxidative stress. Catfish were divided into three groups, 1st control group include 20 fish divided into two tanks each one contain 10 fish, 2nd deltamethrin group, where Fish exposed to deltamethrin in a concentration (0.75 µg/l) and 3rd Vitamin E group, Fish exposed to deltamethrin and vitamin E at a dose of 12 µg/l for successive 4 days.Serum, liver, kidney and Gills were collected for biochemical assays. Tissue oxidative stress biomarkers malondialdhyde (MDA) and catalase activity in liver, kidney and gills tissues, serum liver enzymes (ALT and AST), serum albumin, total protein, urea and creatinine were analysed. RESULTS: Our results showed that 48 h. exposure to 0.75 µg/l deltamethrin significantly (p < 0.05) increased lipid peroxidation (MDA) in the liver, kidney and gills while catalase activity was significantly decreased in the same tissues. This accompanied by significant increase in serum ALT, AST activity, urea and creatinine and a marked decrease in serum albumin and total proteins. CONCLUSIONS: It could be concluded that deltamethrin is highly toxic to catfish even in very low concentration (0.75 µg/l). Moreover the effect of deltamethrin was pronounced in the liver of catfish in comparison with kidneys and gills. Moreover fish antioxidants and oxidative stress could be used as biomarkers for aquatic pollution, thus helping in the diagnosis of pollution. Administration of 12 µg/l α-tocopherol restored the quantified tissue and serum parameters, so supplementation of α-tocopherol consider an effective way to counter the toxicity of deltamethrin in the catfish.

The protective effects of cerium oxide nanoparticles against hepatic oxidative damage induced by monocrotaline.

OBJECTIVE: The objective of the present study was to determine the ability of cerium oxide (CeO(2)) nanoparticles to protect against monocrotaline (MCT)-induced hepatotoxicity in a rat model. METHOD: Twenty male Sprague Dawley rats were arbitrarily assigned to four groups: control (received saline), CeO(2) (given 0.0001 nmol/kg intraperitoneally [IP]), MCT (given 10 mg/kg body weight IP as a single dose), and MCT + CeO(2) (received CeO(2) both before and after MCT). Electron microscopic imaging of the rat livers was carried out, and hepatic total glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPX), glutathione S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) enzymatic activities were quantified. RESULTS: Results showed a significant MCT-induced decrease in total hepatic GSH, GPX, GR, and GST normalized to control values with concurrent CeO(2) administration. In addition, MCT produced significant increases in hepatic CAT and SOD activities, which also ameliorated with CeO(2). CONCLUSIONS: These results indicate that CeO(2) acts as a putative novel and effective hepatoprotective agent against MCT-induced hepatotoxicity.