High-dose Nandrolone Decanoate induces oxidative stress and inflammation in retroperitoneal adipose tissue of male rats

Dr Iguedo Goko Cleanser® is a polyherbal mixture promoted as an effective herbal remedy for numerous diseases. Study aimed to evaluate the toxicity concern of the polyherbal mixture (PHM) on lipid profile and oxidative status in Wistar rats of both gender. Acute toxicity study was conducted using modified method of Lorke. Thirty Wistar rats of bother gender were randomly divided into six groups (5/group) and exposed to the polyherbal mixture for 60 days via oral gavage. Control groups (1 and 4) received 10 mL/kg distilled water, while groups 2-3 and 5-6 received 476.24 and 158.75 mg/kg body weight of Dr Iguedo Goko Cleanser® respectively. On 62nd day, animals were sacrificed under diethyl ether anaesthesia; blood samples were collected by cardiac puncture for biochemical analysis. PHM significantly (p < 0.05) increased high density lipoproteins (HDL) levels in male rats as well as high dose female rats relative to control. However, low dose female rats recorded low HDL levels relative to control. Total cholesterol, triglycerides, low density and very low density lipoprotein levels were significantly reduced in all test groups relative to controls. The low dose males (LDM) had reduced serum glutathione peroxidase (GPX) activity; while increased and decreased GPX and glutathione (GSH) activities were respectively recorded for female rats. Male rats had dose-dependent increase in malondialdehyde. The recorded reductions in serum lipids suggest that the polyherbal mixture may have hypolipidemic potentials. While the increased malondialdehyde as well as decreased GPX and GSH indicate lipid peroxidation and oxidative stress inducing potentials of the PHM. Despite the positive modulation on lipid profile, findings suggest utmost caution on chronic use as its oxidative stress inducing potentials is considerable.

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Protective effects of lycopene on hippocampal neurotoxicity and memory impairment induced by bisphenol A in rats

Human & Experimental Toxicology ◽

10.1177/0960327120909882 ◽

2020 ◽

Vol 39 (8) ◽

pp. 1066-1078 ◽

Cited By ~ 5

Author(s):

EM El Morsy ◽

MAE Ahmed

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Bisphenol A ◽

Antioxidant Properties ◽

Male Rats ◽

Control Group ◽

High Dose ◽

Erk Pathway ◽

Concurrent Treatment ◽

Learning And Cognition

Bisphenol A (BPA) is used to produce polycarbonate plastic and epoxy resins which are used in many consumer products. Most people encounter BPA in their daily routines. However, it has been heavily reported that BPA has a neurotoxic effect. The present study aimed to investigate the effect of lycopene on cognitive deficits induced by a high dose of BPA focusing on mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway, oxidative stress, apoptosis, and memory retrieval in adult male rats. Therefore, 72 rats were divided into four groups: control group, BPA group (50 mg/kg body weight (bw)) 3 days a week for 42 days, lycopene group (10 mg/kg bw) daily for 42 days, and lycopene + BPA group. Concurrent treatment of lycopene with BPA improved the learning and cognition memory in Morris water maze and novel object recognition tests along with an increase in acetylcholine esterase activity as well as inhibition of oxidative stress by restoring reduced glutathione and suppressing malondialdehyde hippocampal level to their normal levels. Mechanistically, lycopene upregulated the protein expression of tyrosine receptor kinase B, which resulted in an upsurge in its downstream cascades MAPK/ERK1/2/cAMP response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway in the hippocampus of BPA-intoxicated rats. Furthermore, concurrent treatment of lycopene with BPA prevented apoptosis by marked decrease in Bcl-2 associated X protein (Bax) gene expression and caspase 3 activity while restoring B-cell leukemia/lymphoma-2 (Bcl-2) gene expression. In conclusion, the present study provided evidence that lycopene exerted a neuroprotective effect against BPA intoxication in hippocampi of rats via its antioxidant properties, activation of MAPK/ERK pathway, and inhibiting a neuronal apoptosis which reflected on improving the learning and cognition memory.

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Antioxidant Effects ofSatureja hortensisL. Attenuate the Anxiogenic Effect of Cisplatin in Rats

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/8307196 ◽

2019 ◽

Vol 2019 ◽

pp. 1-15 ◽

Cited By ~ 3

Author(s):

Igor Kumburovic ◽

Dragica Selakovic ◽

Tatjana Juric ◽

Nemanja Jovicic ◽

Vladimir Mihailovic ◽

...

Keyword(s):

Oxidative Stress ◽

Adverse Effects ◽

Anxiolytic Effect ◽

Optimal Dose ◽

Brain Regions ◽

Male Rats ◽

High Dose ◽

Tissue Samples ◽

Anxiogenic Effect ◽

Antioxidant Effects

Numerous adverse effects of cisplatin-based therapy are usually accompanied by enhanced oxidative damage and cell apoptosis in various tissues. Even neurotoxic manifestations of cisplatin administration, such as the anxiogenic effect, appear along with the increased oxidative stress and apoptotic indicators in certain brain regions. Thirty-five Wistar albino male rats were divided into seven groups: control, cisplatin (received a single dose of cisplatin: 7.5 mg/kg), three groups with oral administration ofSatureja hortensisL. methanolic extract (SH) (low: 50 mg/kg, middle: 100 mg/kg, and high dose: 200 mg/kg) along with cisplatin application, a group with the extract in high dose alone, and a silymarin group (cisplatin and silymarin: 100 mg/kg), in order to evaluate the antioxidant effects of SH on cisplatin-induced increase in the anxiety level. After completing 10-day pretreatments, behavioral testing was performed in the open field and the elevated plus maze, followed by an investigation of oxidative stress and apoptosis parameters in hippocampal tissue samples. Cisplatin administration resulted in anxiogenic-like behavior, increased lipid peroxidation, and proapoptotic markers accompanied by the decline in antioxidant and antiapoptotic defense. The administration of extract alone did not significantly alter any of the estimated parameters. When applied along with cisplatin, SH in a dose of 100 mg/kg induced the significant anxiolytic effect with concomitant recovery of antioxidant and antiapoptotic activity indicators, while both lower and higher doses of the extract failed to improve the adverse effects of cisplatin administration. The beneficial effects of the middle dose of SH were equivalent to the same dose of silymarin, as a “golden standard.” Our results indicate that the antioxidant supplementation with SH in an optimal dose significantly improved the oxidative status and it had antiapoptotic effect in the rat hippocampus disturbed by cisplatin administration, which was accompanied with attenuation of cisplatin-induced anxiogenic effect.

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Ellagic Acid Affects Metabolic and Transcriptomic Profiles and Attenuates Features of Metabolic Syndrome in Adult Male Rats

Nutrients ◽

10.3390/nu13030804 ◽

2021 ◽

Vol 13 (3) ◽

pp. 804

Author(s):

Adéla Kábelová ◽

Hana Malínská ◽

Irena Marková ◽

Olena Oliyarnyk ◽

Blanka Chylíková ◽

...

Keyword(s):

Oxidative Stress ◽

Metabolic Syndrome ◽

Body Weight ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Ellagic Acid ◽

High Fat Diet ◽

Male Rats ◽

High Fat ◽

Brown Adipose

Ellagic acid, a natural substance found in various fruits and nuts, was previously shown to exhibit beneficial effects towards metabolic syndrome. In this study, using a genetic rat model of metabolic syndrome, we aimed to further specify metabolic and transcriptomic responses to ellagic acid treatment. Adult male rats of the SHR-Zbtb16Lx/k.o. strain were fed a high-fat diet accompanied by daily intragastric gavage of ellagic acid (50 mg/kg body weight; high-fat diet–ellagic acid (HFD-EA) rats) or vehicle only (high-fat diet–control (HFD-CTL) rats). Morphometric and metabolic parameters, along with transcriptomic profile of liver and brown and epididymal adipose tissues, were assessed. HFD-EA rats showed higher relative weight of brown adipose tissue (BAT) and decreased weight of epididymal adipose tissue, although no change in total body weight was observed. Glucose area under the curve, serum insulin, and cholesterol levels, as well as the level of oxidative stress, were significantly lower in HFD-EA rats. The most differentially expressed transcripts reflecting the shift induced by ellagic acid were detected in BAT, showing downregulation of BAT activation markers Dio2 and Nr4a1 and upregulation of insulin-sensitizing gene Pla2g2a. Ellagic acid may provide a useful nutritional supplement to ameliorate features of metabolic syndrome, possibly by suppressing oxidative stress and its effects on brown adipose tissue.

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Effects of aqueous extract of polyherbal formulation against hyperthyroidism induced by L-thyroxin in a rat model

Biomedical Research and Therapy ◽

10.15419/bmrat.v5i12.506 ◽

2018 ◽

Vol 5 (12) ◽

pp. 2876-2887 ◽

Cited By ~ 2

Author(s):

Sahar B. Ahmed ◽

Asmaa M. Moghazy ◽

Omar A. Ahmed-Farid ◽

Hassan A. Esebery

Keyword(s):

Oxidative Stress ◽

Thyroid Hormone ◽

Low Dose ◽

Colorimetric Method ◽

The Body ◽

Male Rats ◽

High Dose ◽

Phytochemical Analysis ◽

Oxidative Stress Markers ◽

Stress Markers

Background: Hyperthyroidism is a disorder that occurs when the thyroid gland secretes more thyroid hormone than the body needs. Thyroid hormone is essential for the normal growth and development of normal organs. Polyherb (POH) formulation has proven to be useful in number of diseases and has been used in folk medicine as an anti-hyperthyroidism, anti-oxidant, and appetitestimulating agent. The aim of the study was to evaluate the curative effect of POH against L-thyroxin (LT4)-induced hyperthyroidism in male rats. Methods: Seven groups (10 rats each) were used for this purpose. Determination of phytochemical analysis, oxidative stress markers, brain appetite marker and cell energy marker were determined via high-performance liquid chromatography (HPLC) techniques. Thyroid hormones were detected via ELISA, and liver functions were determined by colorimetric method. Results: The data showed that LT4 altered thyroid function via decreasing serum Thyroid-stimulating hormone (TSH), serum total protein, albumin and globulin, while increasing Triiodothyronine (T3), Thyroxine (T4), and Aspartate aminotransferase (AST). Moreover, oxidative stress markers in liver tissues were increased, via up-regulation of nitric oxide (NO), oxidized glutathione (GSSG), malondialdehyde (MDA), and 8-hydroxy-2'-deoxyguanosine (8OHdG). Meanwhile, glutathione (GSH) and ATP were alleviated; in contrast, metabolites of ADP and AMP were elevated. Neuronal appetite marker in brain tissue was decreased via low serotonin levels. On the other hand, rat groups treated with POH and Carbimazole (CBZ) showed markedly amelioration of hyperthyroidism in rats at low dose only but did not show complete amelioration at high dose of POH. The data were confirmed through histopathological examination of the thyroid. Conclusion: The data obtained demonstrated that POH, at low dose, can be very effective for completely treating hyperthyroidism in rats, and was safer than Carbimazole (CBZ) and ameliorated most signaling pathways and in different tissues.

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Neoplastic and Non-neoplastic Changes in F-344 Rats Treated with Naveglitazar, a γ-Dominant PPAR α/γ Agonist

Toxicologic Pathology ◽

10.1177/0192623309343775 ◽

2009 ◽

Vol 37 (6) ◽

pp. 741-753 ◽

Cited By ~ 19

Author(s):

Gerald G. Long ◽

Vincent L. Reynolds ◽

L. Wayne Dochterman ◽

Thomas E. Ryan

Keyword(s):

Adipose Tissue ◽

Bladder Neoplasms ◽

Urinary Bladder Neoplasms ◽

Female Rats ◽

Male Rats ◽

High Dose ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Associated Lesions ◽

Histologic Types

The carcinogenic potential of naveglitazar, a γ-dominant peroxisome proliferator-activated receptor (PPAR) α/γ dual agonist, was evaluated in a two-year study in F344 rats (0, 0.3, 1.0, or 3.0 mg/kg, males; 0, 0.1, 0.3, or 1.0 mg/kg, females). Increased mortality in male rats of the high-dose group was related to cardiac-associated lesions, neoplasms, and undetermined causes. Degeneration and hypertrophy of the myocardium occurred with dose-responsive increased incidence and severity. Neoplasms with increased incidence included sarcomas in male rats and urinary bladder neoplasms in female rats. Most sarcomas in male rats occurred in the adipose tissue of the subcutis and were diagnosed as fibrosarcomas, with fewer liposarcomas and other histologic types. Non-neoplastic changes in adipose tissue included expansion of adipose tissue in multiple sites, alterations in cytoplasmic vesicular pattern in brown and white fat, increases in stroma and mesenchymal cells, and fibrosis. The severity of chronic progressive nephropathy was decreased in a dose-responsive manner in males, and hyperplasia and neoplasia of the mammary gland were decreased in incidence in females. The adverse effects of cardiotoxicity and increased incidence of neoplasms occurred with dose-responsive incidence and/or severity, and a no-effect level for these effects was not achieved in this study.

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Renoprotective Influence of Pomegranate Juice on Nephrotoxicity Induced by Methotrexate

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i40b32269 ◽

2021 ◽

pp. 103-113

Author(s):

Afnan H. Saaty

Keyword(s):

Oxidative Stress ◽

Inflammatory Cytokines ◽

Antioxidant Property ◽

Renal Tissue ◽

Pomegranate Juice ◽

Male Rats ◽

High Dose ◽

Rheumatic Arthritis ◽

Renal Functions ◽

Pro Inflammatory Cytokines

Methotrexate (Metho) is cytotoxic drug widely used to treat malignant (lymphoma, leukemia, breast cancer) and non-malignant (rheumatic arthritis) diseases. It mediates nephrotoxicity via cellular oxidative stress. Pomegranate juice (POJ) has a potent antioxidant property. This research aimed to assess the potential protective effect of POJ against Metho-induced renal damage in rats. Renal toxicity was induced through intraperitoneal (ip) injection with a single dose of Metho (20 mg/kg). Forty male rats were randomly segregated into 4 groups; each group contained 10 rats. Control (Cont); Metho: rats on the 23rd day injected ip with Metho; POJ (2 ml/kg) +Metho: rats given POJ (2 ml/kg) orally once a day, and on the 23th day injected with Metho ip; and POJ (4 ml/kg) + Metho: rats given POJ (4 ml/kg) orally once a day, and on the 23th day rats were injected with Metho ip. After 5 days of Metho ip. injection, blood samples and renal tissue were obtained. Serum renal functions, ionic electrolytes (sodium and potassium), and pro-inflammatory cytokines were analyzed. Renal oxidative stress and antioxidant enzymes were also measured. Renal tissue were examined microscopically. Metho caused a significant increase in serum renal functions and disturbance in ionic electrolytes. As well as, there was a significant increase in pro-inflammatory cytokines and oxidative stress parameters, with detectable degenerative alteration in glomerulus and renal tissue changes compared with the Cont group. Pretreatment with POJ resulted in preventing biochemical and histopathological alterations induced by Metho. The high dose of POJ (4 ml/kg) was significantly more effective than low dose (2 ml/kg). In conclusion, POJ exerted a potent nephroprotective action and prevent Metho-induced nephrotoxicity. Therefore, POJ may has a beneficial effect in patients receiving Metho therapy.

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Vitamin E and Lactobacillus Provide Protective Effects Against Liver Injury Induced by HgCl2: Role of CHOP, GPR87, and mTOR Proteins

Dose-Response ◽

10.1177/15593258211011360 ◽

2021 ◽

Vol 19 (2) ◽

pp. 155932582110113

Author(s):

Ahlam Alhusaini ◽

Shahad Alghilani ◽

Waad Alhuqbani ◽

Iman H. Hasan

Keyword(s):

Oxidative Stress ◽

Vitamin E ◽

Liver Injury ◽

Histopathological Examination ◽

Male Rats ◽

High Dose ◽

Protective Effects ◽

Sod Activity ◽

Tnf Α

Background and Objective: Mercury is one of the most harmful heavy metals and its toxicity causes severe multi-organ dysfunction. This study was designed to explore novel molecular pathways involved in the hepatoprotective effect of vitamin E (Vit-E) and Lactobacillius plantarum (Lac-B) against mercury toxicity.[Formula: see text] Method: Acute hepatotoxicity was induced by administration of high dose of mercuric chloride (HgCl2) in male rats, Vit-E or/and Lac-B were given along with HgCl2 for 2 weeks. The effects of those antioxidants were studied focusing on their anti-apoptotic, anti-oxidative stress and anti-inflammatory eficacies. Histopathological examinations were also conducted. Results: The administration of HgCl2 induced liver injury which manifested by elevation in serum ALT and AST. Liver MDA, caspase-3 and TNF-α levels were markedly increased; whereas, GSH level and SOD activity were declined. HgCl2 significantly elevated the expressions of hepatic CHOP, GPR87, NF-κB and mTOR. Histopathological examination revealed massive hepatocyte degeneration following HgCl2 administration. Treatment with Vit-E or/and Lac-B restored the normal levels of the previously mentioned parameters, as well as improved hepatic architecture. Conclusion: Vit-E and Lac-B provided protective effect against HgCl2-induced hepatotoxicity via reduction of oxidative stress and inflammation, and downregulation of CHOP, GPR87, NF-κB and mTOR proteins’ expressions.

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Effect of Turmeric and Ginger on Lipid Profile in Male Rats Exposed to Oxidative Stress

International Journal of Pharmaceutical Quality Assurance ◽

10.25258/ijpqa.10.1.23 ◽

2019 ◽

Vol 10 (01) ◽

Author(s):

Eman A. Al-Rekabi ◽

Dheyaa K. Alomer ◽

Rana Talib Al-Muswie ◽

Khalid G. Al-Fartosi

Keyword(s):

Oxidative Stress ◽

Hydrogen Peroxide ◽

Drinking Water ◽

Lipid Profile ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Male Rats ◽

Control Group ◽

Very Low Density Lipoprotein ◽

Low Density

The present study aimed to investigate the effect of turmeric and ginger on lipid profile of male rats exposed to oxidative stress induced by hydrogen peroxide H2O2 at a concentration of 1% given with consumed drinking water to male rats. Methods: 200 mg/kg from turmeric and ginger were used, and the animals were treatment for 30 days. Results: the results showed a significant increase in cholesterol, triglycerides, low density lipoprotein (LDL), very low density lipoprotein (VLDL), whereas it explained a significant decrease in high density lipoprotein (HDL) of male rats exposed to oxidative stress when compared with control group. the results showed a significant decrease in cholesterol, triglycerides, (LDL), (VLDL), whereas it explained a significant increase in (HDL) of rats treated with turmeric and ginger at dose 200 mg/kg when compared with male rats exposed to oxidative stress.

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