Mervat E. Asker

Hyperhomocysteinaemia and cardiovascular risk in female ovariectomized rats: role of folic acid and hormone replacement therapy

Hyperhomocysteinaemia is an independent risk factor for arteriosclerosis, recurrent thromboembolic complications and osteoporosis. After menopause, a high level of total homocysteine seems to be secondary to the altered hormonal status. Hormone replacement therapy (HRT) limits the development of coronary artery disease through a variety of mechanisms. One such mechanism is through affecting homocysteine metabolism. Folate and vitamin B12 deficiencies are considered to be major risks for hyperhomocysteinaemia. This study, therefore, was undertaken to examine whether lowering homocysteine with HRT or folic acid in ovariectomized rats could attenuate cardiovascular complications. Sixty sexually mature female Wistar rats were ovariectomized. Three weeks later, they were treated with estradiol (15 μg kg−1 every two weeks, i.m.) or folic acid (90 μg daily, orally), either alone or in a combined form for four weeks. In addition, groups of ovariectomized rats (positive control) and healthy rats (negative control) were given cottonseed oil. Blood samples were then collected for serum and plasma separation. Serum total homocysteine, folate, estradiol, plasma nitric oxide (NO), lipid profile, and susceptibility of non‐high‐density‐lipoprotein cholesterol (non HDLC) contentto oxidation were determined. In ovariectomized rats, hyperhomocysteinaemia was established and associated with significant increments of both atherogenic indexes (total cholesterol/HDLC, low‐density‐lipoprotein cholesterol (LDLC)/HDLC) and susceptibility of their non HDLC to oxidation. However, plasma NO, serum folate, and estradiol levels significantly decreased. HRT and folic acid significantly reduced total homocysteine and susceptibility of non HDLC to oxidation and increased plasma NO content. Moreover, a significant negative correlation was found between total homocysteine versus folate and estradiol (r = − 0.5, P< 0.01; r = − 0.25, P< 0.05, respectively). Meanwhile, a positive correlation with the susceptibility of lipoprotein to oxidation was observed (r = 0.85, P< 0.001). In conclusion, a low folate level is found to be associated with elevated total homocysteine. Folic acid supplementation, either individually or in a combined form with HRT, has a beneficial effect in low estrogen status subsequent to ovariectomy.

Pioglitazone Attenuates Cardiac Fibrosis and Hypertrophy in a Rat Model of Diabetic Nephropathy

Pioglitazone has been demonstrated to have beneficial effects on cardiovascular outcomes. However, little is known about its effect on cardiac remodeling associated with diabetic nephropathy. Therefore, this study was designed to study the effects of pioglitazone on cardiac fibrosis and hypertrophy in a rat model of diabetic nephropathy. For this purpose, male Wistar albino rats were randomly assigned into 4 groups (n = 10 per group): normal (N) group, diabetic (D) group, diabetic nephropathic (DN) group received an equal amount of vehicle (0.5% carboxy methyl cellulose), and diabetic nephropathic group treated by oral administration of pioglitazone (10 mg/kg per d) for 4 weeks. Diabetic nephropathy was induced by subtotal nephrectomy plus streptozotocin (STZ) injection. The results revealed that DN rats showed excessive deposition of collagen fibers in their cardiac tissue, along with a marked myocyte hypertrophy. This was associated with a dramatic upregulation of cardiac transforming growth factor-β1 (TGF-β1) gene. Furthermore, the gene expression of matrix metalloproteinase 2 (MMP-2) decreased, while the gene expression of tissue inhibitor of metalloproteinase 2 (TIMP-2) increased in the hearts of DN rats. In addition, enhanced lipid peroxidation and myocardial injury, evidenced by a significant increase in their serum creatine kinase-MB level were observed in DN rats. All these abnormalities were ameliorated by pioglitazone administration. Our findings suggest that upregulation of cardiac TGF-β1 gene along with the imbalance between MMP-2 and TIMP-2 expressions is critically involved in cardiac fibrosis associated with diabetic nephropathy. Pioglitazone can ameliorate cardiac remodeling by suppressing the gene expression of TGF-β1 and regulating the MMP-2/TIMP-2 system.

Nicotine and vascular endothelial dysfunction in female ovariectomized rats: role of estrogen replacement therapy.

Objectives  The protective effects of estrogen replacement therapy (ERT) against oxidative injury and endothelial dysfunction in the aortic tissues induced with nicotine in ovariectomized (OVX) rats were investigated.

Haemostatic risk factors in dyslipidemic rabbits: role of 10-dehydrogingerdione as a new hypolipemic agent

Micro and macrovascular complications occurring during hyperlipidemia are mostly attributed to haemostatic impairment and vascular endothelial dysfunction. Cholesteryl ester transfer protein (CETP) inhibitors have been emerged recently as promising hypocholesterolemic agents to confer protection against lipid-mediated atherosclerosis. Therefore, 10-dehydrogingerdione (DHGD), a novel CETP inhibitor isolated from ginger rhizomes, was selected as a natural product in the present study to illustrate its effect on haemostatic impairment associated with hyperlipidemia as compared to a currently used hypocholesterolemic agent, atorvastatin (ATOR). Rabbits were fed a high cholesterol diet (HCD) and divided into three groups. One group served as control group while the other groups received DHGD or ATOR. Dyslipidemic rabbits showed a significant increase in serum endothelin-1, ischemia modified albumin, plasminogen activator inhibitor-1, prothrombin fragments (1+2) and plasma fibrinogen along with a decrease of nitric oxide level in serum. Daily administration of ATOR or DHGD significantly decreased the aforementioned coagulation and ischemia biomarkers and increased serum nitric oxide. DHGD (natural) results seem to be more remarkable as compared to ATOR (synthetic).

Beneficial effects of pioglitazone against cardiovascular injury are enhanced by combination with aliskiren in a rat model of diabetic nephropathy

Objectives  Aliskiren is the first in a new class of orally active direct renin inhibitors, approved for the treatment of hypertension. However, the efficacy of aliskiren in diabetic cardiovascular complications remains to be defined. This study aimed to test the hypothesis that aliskiren may enhance the beneficial effects of pioglitazone against cardiovascular injury associated with diabetic nephropathy.

Modulation of brain insulin signaling in Alzheimer’s disease: New insight on the protective role of green coffee bean extract

Objective: Alzheimers disease (AD), a neurodegenerative disorder, involves brain insulin signaling cascades and insulin resistance (IR). Because of limited treatment options, new treatment strategies are mandatory. Green coffee bean extract (GCBE) was reported to attenuate IR and improve brain energy metabolism. We aimed to investigate the possible use of GCBE as a prophylactic strategy to delay the onset of AD or combined with pioglitazone (PIO) as a strategy to retard the progression of AD. Methods: Rats received 10% fructose in drinking water for 18 weeks to induce AD. GCBE-prophylactic group received GCBE for 22 weeks started 4 weeks prior to fructose administration. The PIO group treated with PIO for 6 weeks started on week 12 of fructose administration. The GCBE+PIO group received GCBE for 22 weeks started 4 weeks prior to fructose administration and treated with PIO for the last 6 weeks of fructose administration. Results: Pretreatment with GCBE, either alone or combined with PIO, alleviated IR-induced AD changes. GCBE improved cognition, decreased serine phosphorylation of insulin receptor substrate, increased phosphoinositol-3 kinase (PI3K) activity and protein kinase B (Akt) gene expression, decreased glycogen synthase kinase-3β (GS3Kβ) gene expression and Tau hyperphosphorylation. Discussion: GCBE exerted neuroprotective effects against IR-induced AD mediated by alleviating IR and modulating brain insulin signaling cascade.

Assessment of anthracyclin-related hyperlipidemia taurine or PDE4 inhibitor during endotoxemia

No Abstract. The Egyptian Journal of Biochemistry and Molecular Biology Vol. 23(1) 2005: 1-19