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.

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.

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.

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.