ESTROGENS IMPROVE THE CARDIOVASCULAR ALTERATIONS IN FRUCTOSE-INDUCED INSULIN RESISTANT OVARIECTOMIZED RATS

Objective: The present study aimed to investigate the possible improving effects of 17-β estradiol (EST) and genistein (GEN) on the cardiovascular changes associated with fructose (21% in drinking water for 8 weeks)-induced insulin resistance.Methods: Sham-operated and ovariectomized mature female rats were included in this study. Insulin-resistant ovariectomized animals were sc treated with EST (100 µg/kg) or GEN (1 mg/kg) on the daily basis for 21 consecutive days.Results: Induction of insulin resistance in both sham-operated and ovariectomized rats decreased the vascular responsiveness of isolated aortic rings towards the vasoconstrictor norepinephrine and the vasodilator acetylcholine (Ach) with no changes towards the vasodilator sodium nitroprusside. Fructose-induced insulin resistance was also associated with an elevation in the blood pressure (BP) with decreased serum level of nitric oxide (NO). Treatment of insulin-resistant ovariectomized rats with either EST or GEN improved the vascular responsiveness of isolated aortic rings towards Ach and succeeded to reduce the elevated BP. Moreover, both EST and GEN decreased the insulin resistance/compensatory hyper insulinaemia. Treatment with EST increased serum NO level.Conclusion: EST and GEN have the ability to improve the endothelium-dependent relaxation in insulin-resistant ovariectomized rats and modulate the elevated BP.Â

Protection by low-dose γ radiation on doxorubicin-induced nephropathy in rats pretreated with curcumin, green tea, garlic or l-carnitine

The protective potentials of a single exposure to 0.3 Gy of γ radiation alone or with previous treatment with certain natural products with antioxidants activity, namely curcumin (50 mg/kg, i.p.), green tea (300 mg/kg, p.o.), garlic (100 mg/kg, p.o.) or l-carnitine (40 mg/kg, i.p.) against doxorubicin (DOX)-induced nephropathy in rats were studied. Natural products were administered daily for 14 successive days followed by single i.p. injection of DOX (5 mg/kg). Rats were subjected to whole body γ radiation, 1 day before DOX administration. Serum levels of creatinine, urea, uric acid, low density lipoprotein (LDL-C), high density lipoprotein (HDL-C) cholesterols, total proteins and albumin as well as renal concentrations of reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS), nitric oxide (NO) and calcium (Ca) were determined. Irradiation provided significant protections against DOX-induced changes in all measured parameters, except renal Ca content. All the test natural products significantly improved radiation-induced protection against renal lipid peroxidation. l-Carnitine markedly augmented the protection toward changes in renal GSH, NO and Ca concentrations. Curcumin increased the protection toward changes in serum albumin and renal GSH and NO concentrations, while garlic increased the protection toward changes in serum LDL-C level. It could be concluded that low-dose γ radiation could provide prophylaxis against DOX-induced nephropathy which might be augmented by the use of certain natural antioxidants

Protective effects of atorvastatin and quercetin on isoprenaline-induced myocardial infarction in rats

Myocardial infarction (MI) continues to be a major public health problem in the world. Statins exhibit cardio-protective effects by several mechanisms beyond their lipid lowering activity. Quercetin is a natural flavonoid that possesses significant anti-oxidant and antiinflammatory activities. The present study aimed to investigate the effects of pretreatment with atorvastatin (10 mg/kg) and quercetin (50 mg/kg), as well as their combination on isoprenaline-induced MI in rats. Markers chosen to assess cardiac damage included serum activity of creatine kinase-MB (CK-MB) and serum level of cardiac troponin-I (cTn-I), as well as oxidative stress and inflammatory biomarkers including serum levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10) as well as cardiac contents of lipid peroxides, reduced glutathione (GSH), and nitrite. Furthermore, ECG monitoring and histological examinations of cardiac tissues were done. Isoprenaline increased serum CK-MB activity and cTn-I level as well as inflammatory and oxidative stress biomarkers. In addition, it produced ST-segment elevation and degenerative changes in heart tissues. Pretreatment with atorvastatin suppressed significantly the elevated levels of cTn-I, CRP, TNF-α, and IL-10 in serum coupled with reduction in cardiac lipid peroxides; however, it increased cardiac nitrite content. Quercetin decreased isoprenaline-induced changes in oxidative stress and inflammatory biomarkers with marked improvement in ECG and histopathologic alterations. Combination of quercetin with atorvastatin resulted in similar protective effects. In conclusion, quercetin can be regarded as a promising cardio-protective natural agent in MI alone or combined with atorvastatin

Isoprenaline-Induced Myocardial Infarction in Rats: Protective Effects of Hesperidin

Myocardial infarction is amongst the most common causes of death worldwide. The present study aimed to investigate the cardioprotective effect of hesperidin (200 mg/kg) either individually or in combination with atorvastatin (10 mg/kg), as a reference standard, in isoprenaline-induced myocardial infarction in rats. Markers chosen to assess cardiac damage included serum activity of creatine kinase-MB (CK-MB) and serum level of cardiac troponin-I (cTn-I), oxidative stress biomarkers including cardiac contents of malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (NO) as well as serum levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10). Furthermore, ECG monitoring and histologic examinations of cardiac tissues were done. Isoprenaline increased CK-MB activity as the well the levels of cTn-I, inflammatory and oxidative stress biomarkers. In addition, it produced ST segment elevation and degenerative changes in heart tissues. The obtained data revealed that pretreatment with hesperidin alone or in combination with atorvastatin significantly decreased the elevated activity of serum CK-MB as well as serum levels of cTn-I, CRP, TNF-α and IL-10 coupled by a reduction in cardiac lipid peroxides and NO content. Moreover, both treatments resulted in marked improvement in isoprenaline-induced ECG and histopathologic changes. In conclusion, hesperidin can be regarded as a promising cardioprotective natural agent in myocardial infarction when used alone or combined with atorvastatin

Effect of Long-Term Treatment with Fluoxetine, Clomipramine and St. John's Wort Extract on Bone Turnover in Female Irradiated Rats

Aim: The study aimed at evaluating the bone turnover rate in irradiated female rats treated daily with fluoxetine, clomipramine or St. John’s wort extract for 8 weeks. Material and Methods: 40 rats were randomly classified into 5 experimental groups: normal, irradiated control, irradiated fluoxetine, irradiated clomipramine and irradiated St. John’s wort extract treated groups. The irradiated animals were exposed to a total dose of 15 Gy, fractionated over 5 weeks to small doses each of 1 Gy (day after day). Bone turnover rate biomarkers [serum osteocalcin (OC), urinary hydroxyproline/ creatinine ratio (Hpr/ Cr), urinary calcium/creatinine ratio (Ca/Cr)], hypothalamic pituitary adrenal [serum corticosterone], thyroid activities [serum thyroxin (T4) and thyrotrophin (TSH)], antioxidant [serum total antioxidant capacity (TAC) and malondialdehyde (MDA)] and pro-inflammatory biomarkers [serum tumor necrosis factor-alpha (TNF-α)] were done after 8 weeks from the 1st exposure to radiation. Histopathological investigations were also performed. Results: The present results revealed that irradiation induced a significant decrease in serum OC by 43.6%, and a significant increase of Hpr/ Cr and Ca/Cr by 186.4% and 192.4%, respectively. Irradiated rats showed also a significant increase in serum corticosterone, TNF-α and MDA as well as a significant decrease in serum T4, TSH levels and TAC. Treatment of irradiated rats with St. John’s wort extract, fluoxetine or clomipramine ameliorated most of the changes caused by bone-irradiation. The latter findings were confirmed by histological examination of bone tissue. Conclusions: St. John’s wort extract offers a therapeutic potential on bone comparable to traditional antidepressants like fluoxetine or clomipramine in irradiated female rats

Prophylactic and curative anti-ulcerogenic activity and the possible mechanisms of action of some desert plants

The present study aimed to evaluate the anti-ulcerogenic activities and the possible mechanisms of action of seven desert plants from different families. Conyza dioscoridis (L.) Desf. (Asteraceae), Euphorbia hirta L. (Euphorpiaceae), Origanum syriacum L., Salvia lanigera L. (Lamiaceae), Sisymbrium irio L., Solanum nigrum Linn. (Solanaceae) and Solenostemma arghel (Del.) Hayne. (Asclepiadaceae), were tested using prophylactic and curative models of absolute ethanol-induced ulcer, at three doses (125, 250 & 500 mg/kg) of each extract. The investigated extracts possessed dose dependent anti-ulcerogenic activities in both models, with LD50 higher than 5 g/kg. The most effective extracts were C. dioscoridis and S. irio with percent protection of control ulcer; 91.1% and 85.4% respectively. The antisecretory activity of both C. dioscoridis and S. irio appears to be mainly related to the suppression of gastrin release. The in vitro potential radical (DPPH) scavenging activities of the investigated extracts were well supported with the reduction in gastric MDA (50.6% and 43.3%) and enhancing the level of reduced GSH (2.84, 2.59 mg/g tissue) for C. dioscoridis and S. irio respectively. In addition, suppression of the inflammatory mediator TNF-α may be one of the possible mechanisms of action. The alcohol extracts of C. dioscoridis and S. irio showed no alteration on liver and kidney functions. Phytochemical screening of the investigated extracts revealed the presence of flavonoids, tannins and sterols which could be related to the activities

Effect of Nigella sativa and wheat germ oils on scopolamine-induced memory impairment in rats

Aim: To investigate the possible memory enhancing effects of Nigella sativa oil (NSO) and wheat germ oil (WGO) on scopolamine-induced amnesic rats. Methods: Male Wistar rats received either saline or scopolamine (16 mg/kg, i.p.). The other three groups were pretreated with NSO (1 ml/kg, p.o.), WGO (170 mg/kg, p.o.) or donepezil used as a reference drug (10 mg/kg, p.o.) for 14 days before scopolamine injection. Cognitive and biochemical measurements were then assessed. Principal results: NSO and WGO treated rats significantly reversed scopolamine-induced deficit of spatial and non-spatial working memory impairment in the T maze alternation task and object recognition test, respectively. Administration of NSO prior to scopolamine showed a significant decrease in malondialdehyde (MDA) and increase in Glutathione (GSH) brain contents to be similar to that observed in donepezil group. It did not alter cholinesterase activity and showed a significant decrease in brain tumor necrosis factor-alpha (TNF-α) content to be similar to donepezil-treated rats. Scopolamine-demented rats pretreated with WGO did not change MDA brain content significantly as compared to scopolamine and donepezil groups. WGO-treated rats showed a significant increase in GSH to a level similar to that observed in the donepezil group, it showed a significant decrease in cholinesterase activity as compared to scopolamine group and significantly elevated brain TNF-α content when compared to donepezil group. Conclusions: Memory enhancing effect of NSO in the present study might be due to its antioxidant and anti-inflammatory activities, while that of WGO might be via its antioxidant and anticholinesterase activities

Beneficial effects of thymoquinone and omega-3 on intestinal ischemia/reperfusion-induced renal dysfunction in rats

Intestinal ischemia–reperfusion (II/R) is a complex phenomenon causing local and remote tissue destruction and multiple-organ dysfunction. The technique has been used by many authors to produce certain organ dysfunctions. This study is to investigate the possible beneficial effects of thymoquinone and omega-3 separately in II/R-induced renal dysfunction in rats. Sixty-four Wistar albino rats were randomly allocated into four experimental groups namely sham control, II/R control, thymoquinone and omega-3 each group pre-treated separately. II/R model was established by clamping the superior mesenteric artery (SMA) for 30 min followed by 60 min reperfusion. Serum level of creatinine was measured. Renal tissue contents of malodialdehyde (MDA) and reduced glutathione (GSH) as well as myeloperoxidase (MPO), tumor necrosis factor alpha (TNF-α) and superoxide dismutase (SOD) activities were measured. Apoptosis in renal tissue cells was determined by immunohistochemical analysis of caspase-3. Renal histopathological examination was carried out. II/R elevated serum creatinine level. In-addition, renal tissue content of GSH and SOD activity were decreased. However renal tissue content of MDA and MPO activity were increased. Immunohistochemical analysis showed remarkable activation of caspase-3 in renal tissue. Histopathological examination revealed definite alterations after II/R. Pre-treatment with thymoquinone and omega-3 resulted in increased renal tissue content of GSH and SOD activity. The results revealed significant decrease in renal tissue content of MDA as well as MPO activity. Test drugs decreased the activity of caspase-3 through immunohistochemical examination. Thymoquinone and omega-3 corrected the reported histopathological changes induced by II/R. Depending on the obtained results in the present study it could be concluded that thymoquinone and omega-3 have beneficial effects on II/R-induced renal dysfunction in rats. The protective potential could be attributed to the antioxidant, antiapoptotic and anti-inflammatory effects of test drugs