Therapeutic effects of thymoquinone or capsaicin on acrylamide-induced reproductive toxicity in rats mediated by their effect on oxidative stress, inflammation, and tight junction integrity.

In the field of environmental toxicology, endocrine-disrupting effects have become a major concern. The present research set out to investigate the possible reproductive toxicity of acrylamide. The research was also expanded to explore the protective effects of two nutraceuticals, thymoquinone (TQ) and capsaicin, against acrylamide-induced reproductive toxicity. Six groups of sixty male albino rats were created. Group 1 was used as a control. Rats were administered a daily dose of acrylamide and acted as the model in Group 2. TQ was provided to rats once a day in Group 3. Capsaicin was administered to rats once a day in Group 4. TQ was given once daily to rats exposed to acrylamide in Group 5. Rats were given capsaicin once a day for eight weeks after being exposed to acrylamide in Group 6. Acrylamide induced oxidative stress, testicular NF-κB/p65 expression, and down-regulated the expression of occludin, all of which can contribute to its testicular toxicity, while TQ or capsaicin removes all of these toxicity signs. TQ and capsaicin have shown efficacy in alleviating all of the acrylamide's toxic insults in the current reproductive toxicity model. Both nutraceuticals upregulated the expression of occludin in testicular tissue and restored tight junction integrity, in addition to their well-known antioxidant and anti-inflammatory effects, which were confirmed in this study.

Evaluation of the cardioprotective effect of Casuarina suberosa extract in rats.

The aim of the current study was to examine and compare the cardioprotective activities of the chloroform and petroleum extracts the leaves of Casuarina suberosa in isoproterenol (ISO)-induced cardiac tissue oxidative stress. Rats were categorized into 6 groups as follows: control group, vehicle or Tween 80-treated group, ISO-treated group, chloroform extract + ISO treated group, petroleum ether extract + ISO treated group and Reference drug (Captopril) + ISO treated group. ISO injection significantly (p < 0.05) increased the activities of cardiac marker enzymes (CK-MB, LDH, ALT, and AST), cardiac troponin-I, levels of lipid peroxides (MDA), nitric oxide (NO), and vascular endothelial growth factor (VEGF), serum angiotensin-converting enzyme (ACE) activity and neutrophil infiltration marker; myeloperoxidase (MPO) in the cardiac tissues. Pretreatment with chloroform or petroleum ether extracts significantly (p < 0.05) prevented the ISO-induced alteration; they upregulated VEGF expression. Histopathological findings corroborated biochemical results. These extracts exerted a cardioprotective effect by alleviating oxidative stress.

Possible protective effect of TNF-α inhibition and triad NO/cGMP/VEGF activation on gastric ulcer in rats.

Peptic ulcers are one of the world's major gastrointestinal disorders, embracing both gastric and duodenal ulcers, and affecting 10% of the world population. The current study aimed to investigate the possible protective effect of tadalafil and pentoxifylline (PTX) on indomethacin-induced peptic ulcers. Male albino rats were divided into five groups: control group; ulcerated group; Indomethacin + Tadalafil, in which animals were pretreated with tadalafil orally before indomethacin; Indomethacin+ PTX, in which animals were pretreated with PTX orally before indomethacin; and Indomethacin + Tadafil + PTX. Indomethacin treatment revealed histopathological changes and ulcer scoring and ulcer index were markedly increased. Serum levels of prostaglandin and heme oxygenase-1 were significantly decreased. The ulcerogenic also induced marked oxidative stress as evident from the increased malondialdehyde, decreased in gastric glutathione content and superoxide dismutase activity, while the gastric myeloperoxidase was increased. Gastric nitric oxide content was decreased and the expression of vascular endothelial growth factor was downregulated while the tumor necrosis factor α (TNF-α) level was dramatically increased. Pretreatment of the ulcerative group by either tadalafil or PTX or their combination improved all these pathological changes. Tadalafil or PTX may have a role in protecting gastric mucosa damage caused by indomethacin which may be useful in the future for the treatment of gastric ulceration.

Attenuative Effects of Fluoxetine and Triticum aestivum against Aluminum-Induced Alzheimer's Disease in Rats: The Possible Consequences on Hepatotoxicity and Nephrotoxicity.

BACKGROUND: Alzheimer's disease (AD) is a chronic neurological illness that causes considerable cognitive impairment. Hepatic and renal dysfunction may worsen AD by disrupting ß-amyloid homeostasis at the periphery and by causing metabolic dysfunction. Wheatgrass (Triticum aestivum) has been shown to have antioxidant and anti-inflammatory properties. This work aims to study the effect of aluminum on neuronal cells, its consequences on the liver and kidneys, and the possible role of fluoxetine and wheatgrass juice in attenuating these pathological conditions. METHOD: Rats were divided into five groups. Control, AD (AlCl3), Fluoxetine (Fluoxetine and AlCl3), Wheatgrass (Wheatgrass and AlCl3), and combination group (fluoxetine, wheatgrass, and AlCl3). All groups were assigned daily to different treatments for five weeks. CONCLUSIONS: AlCl3 elevated liver and kidney enzymes, over-production of oxidative stress, and inflammatory markers. Besides, accumulation of tau protein and Aß, the elevation of ACHE and GSK-3ß, down-regulation of BDNF, and ß-catenin expression in the brain. Histopathological examinations of the liver, kidney, and brain confirmed this toxicity, while treating AD groups with fluoxetine, wheatgrass, or a combination alleviates toxic insults. CONCLUSION: Fluoxetine and wheatgrass combination demonstrated a more significant neuroprotective impact in treating AD than fluoxetine alone and has protective effects on liver and kidney tissues.

Effect of gamma radiation on combination therapy of certain antiepileptic drugs in rats.

The current study was designed to estimate the effect of υ-radiation on male rats pretreated with Levetiracetam (LEV) and/or Oxcarbazepine (OXC). Poly-treatment of rats with LEV, OXC and υ-radiation showed a significant elevation in the activity of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and isoenzyme creatinine kinase-MB (CK-MB) along with, an increase in the level of creatinine, urea, cardiac troponin (cTnI) and glutamate. These increases were associated with a decrease in acetylcholine (Ach) and υ-aminobutyric acid (GABA) levels. The data further revealed a significant increase of the apoptotic mediators tumor necrosis factor alpha (TNF-α) and brain caspase3 as well as, alterations in the oxidative stress parameters. The Results of the histopathological examination of liver, kidney, heart and brain tissues indicated coincidence with those recorded by the biochemical analysis. It seems promising to conclude that the exposure to υ-radiation intensified the deleterious and detrimental effect of dual treatment of LEV and OXC in rats.

Comparative study of antifibrotic activity of some magnesium-containing supplements on experimental liver toxicity. Molecular study.

INTRODUCTION: Liver fibrosis is the excessive accumulation of extracellular matrix (ECM) proteins including collagen that occurs in most types of chronic liver diseases. This study aimed to investigate and compare the therapeutic efficacy of different magnesium (Mg)-containing supplements (formulations A, B, and C) on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. METHODS: Liver fibrosis was induced by intraperitoneal injection of rats with CCl4 (1:1 in olive oil, 2 mL/kg, three times/week) for 4 weeks, and then rats were orally treated with different Mg-containing supplements (formulations A, B, and C) once daily for another one month. Liver fibrosis was quantified by evaluation of expressions of Collagen I, transforming growth factor ß-1 (TGFß1), platelet-derived growth factor-C (PDGF-C), nuclear factor kappa-ß (NF-κß), and measurement of hepatic collagen (hydroxyproline) level. Also, malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH) level, superoxide dismutase (SOD), and glutathione-S-transferase (GST) activities were estimated. RESULTS: CCl4 administration significantly elevated expressions of the studied genes, hepatic hydroxyproline, MDA, and NO levels and caused depletion of GSH level, decreased SOD, and GST activities when compared with those of their corresponding control, p < 0.05. All magnesium supplements significantly inhibited expressions of the studied genes and attenuated the hepatic hydroxyproline level as compared with those of CCl4-treated group; p < 0.05; for NF-κß, the highest inhibition was by formulations B and C. Regarding Collagen I, TGFß1, and hepatic hydroxyproline content, the highest inhibition was by Formulation C, and Formulation A revealed highest inhibition for PDGF-C. All magnesium supplements revealed normalization of oxidant and antioxidants parameters. Histopathological examination supports the biochemical and molecular findings. CONCLUSION: Mg supplements were effective in the treatment of hepatic CCl4-induced fibrosis-rat model.

Evaluation of biochemical effects of Casuarina equisetifolia extract on gentamicin-induced nephrotoxicity and oxidative stress in rats. Phytochemical analysis.

Nephrotoxicity is defined as renal dysfunction that arises as result of exposure to external agents such as drugs and environmental chemicals. The present work was undertaken to carry out the phytochemical study and nephroprotective activity of methanolic extract of Casuarina equisetifolia leaves in gentamicin-induced nephrotoxicity in Wistar rats. Flavonoids and phenolic acids were identified and quantified using high performance liquid chromatography. Subcutaneous injection of rats with gentamicin (80 mg/kg body weight/day) for six consecutive days induced marked acute renal toxicity, manifested by a significant increase in serum urea, creatinine and uric acid levels, along with a significant depletion of serum potassium level, compared to normal controls. Also oxidative stress was noticed in renal tissue as evidenced by a significant decrease in glutathione level, superoxide dismutase, glutathione-S-transferase activities, also a significant increase in malondialdehyde and nitric oxide levels when compared to control group. Administration of plant extract at a dose of 300 mg/kg once daily for 4 weeks restored normal renal functions and attenuated oxidative stress. In conclusion, Casuarina equisetifolia leaves extract ameliorates gentamicin-induced nephrotoxicity and oxidative damage by scavenging oxygen free radicals, decreasing lipid peroxidation and improving intracellular antioxidant defense, thus extract may be used as nephroprotective agent.

Lycopene and Chrysin through Mitigation of Neuroinflammation and Oxidative Stress Exerted Antidepressant Effects in Clonidine-Induced Depression-like Behavior in Rats.

Depression is a severely debilitating psychiatric disorder that influences more than 15% of the population worldwide. It has been demonstrated that it is associated with a high risk of developing other diseases such as cardiovascular diseases, diabetes, stroke, epilepsy, and cancer. The current study examines the possibility of chrysin and lycopene having an antidepressant effect in a rat model of depression induced by clonidine, as well as the mechanisms underlying this effect, including the role of neuroinflammation and oxidative stress. Rats were allotted into seven groups. The rats in group 1 served as a control. Group 2 received lycopene only. Group 3 was provided chrysin only. Group 4 was administered clonidine and served as the model. Group 5 was offered lycopene and clonidine. Group 6 was administered chrysin and clonidine. Group 7 was given FLX and clonidine and represented the standard. The experiment lasted two weeks, during which behavioral, biochemical, histopathological, and immunohistochemical measurements were performed. Lycopene and chrysin were used to correct the concentrations of noradrenaline and serotonin hippocampal tissue concentrations. These findings were also improved by immunohistochemical analysis of GFAP, VEGF, caspase3, and histopathological examinations, in which pretreatment of rats with lycopene and chrysin reversed all clonidine-induced alterations. The current research demonstrates that lycopene and chrysin have an auspicious antidepressant effect against clonidine that provoked behavioral hopelessness in rats. Manipulating oxidative stress, inflammation, and apoptosis may partially represent the corrective mechanism for the neuroprotective actions against the depressive effect of clonidine.

Evaluation of the anti-atherogenic potential of Egyptian artichoke leaf extract in hypercholesterolemic rats.

OBJECTIVES: The current research seeks to assess the anti-atherogenic activity of Egyptian artichoke leaf extract in hypercholesterolemic rats. MATERIALS AND METHODS: Male albino rats were categorized into five groups; control group, high cholesterol diet treated group (HCD), HCD + low dose of artichoke, HCD + high dose of artichoke and HCD + Atorvastatin. RESULTS: Both doses of artichoke extract significantly decreased the concentration of serum cholesterol, triglycerides, and LDL-C in HCD rats as compared to that of their matching controls, p < .05. The treatment with artichoke led to the inhibition of the liver hydroxymethylglutaryl-CoA (HMG-CoA) reductase. Besides, the extract was proven to be cardioprotective effective by increasing antioxidant activity. The effect of the highest dose of artichoke was more apparent than the effect of the lowest one. The biochemical data was reinforced by the histopathological studies. DISCUSSION AND CONCLUSION: Artichoke may act as a natural source for the elimination of cardiovascular ailments.

Protective effect of cardamonin against acetic acid-induced ulcerative colitis in rats.

BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease with significant morbidity. Cardamonin is a natural chalcone derivative with considerable anti-inflammatory activity. Herein, the potential protective effect of cardamonin against UC was tested in a rat model. METHODS: Rats were given 10 or 30mg/kg/day of cardamonin orally for 14days before induction of UC. On the 14th day of treatment, UC was induced by intrarectal instillation of 2ml 3% acetic acid. Twenty four h after acetic acid instillation, rats were sacrificed and colons were analyzed by macroscopic and histopathological examination. Colon lipid peroxidation was examined by biochemical evaluation of malondialdehyde (MDA). Myeloperoxidase (MPO), iNOS, NF-κB, TNFα levels were measured by ELISA. Moreover, caspase-3 and COX-2 were assessed by immunohistochemical analysis. RESULTS: Cardamonin at 10 and 30mg/kg decreased the disease activity index and macroscopic damage index scores, and significantly reduced histopathological deterioration. Additionally, cardamonin reduced levels of MPO, iNOS, NF-κB, TNFα and MDA (p<0.05). Immunohistochemistry revealed down-regulation of COX-2 and caspase-3 in groups treated with cardamonin. CONCLUSION: Cardamonin has a protective effect against acetic acid-induced colitis. This effect may be due to reducing inflammation, oxidative stress and apoptosis.