Nayira A. Abdel Baky

Nitric oxide pros and cons: The role of l-arginine, a nitric oxide precursor, and idebenone, a coenzyme-Q analogue in ameliorating cerebral hypoxia in rat

Evidence exists that nitric oxide (NO) may mediate both protective and pathological responses during brain hypoxia (HP). Reactive oxygen species have also been implicated in the pathophysiological response of the brain tissues to HP. Therefore, this study investigated whether a NO precursor, l-arginine (l-arg), a free radical scavenger, idebenone (ID), and their combination would reduce neurological injury resulting from hemic hypoxia (HP) in rats. Adult male Wistar albino rats were injected with sodium nitrite (60 mg/kg, s.c.) to establish hemic hypoxia. ID (100 mg kg(-1), i.p.) and/or l-arg (100 mg kg(-1), i.p.) were administrated 24 and 1h prior to sodium nitrite intoxication, respectively. Hypoxia significantly decreased hemoglobin concentration, while significantly increased serum lactate dehydrogenase (LDH), creatine phosphokinase (CPK), total nitrate/nitrite, sialic, and uric acids concentrations. Moreover, brain lipid peroxides were significantly enhanced, while reduced glutathione, l-ascorbic acids, adenosine triphosphate (ATP) contents, and the activities of catalase and superoxide dismutase, were significantly reduced in the brain tissue. Pretreatment with either ID or l-arg altered the majority of the above-mentioned biochemical changes in hypoxic rats. Additionally, the combination of these two agents significantly reduced injury marker enzyme activities as well as serum sialic, and uric acids level (P>0.05 vs. control). Moreover, this combination exerted a synergistic antioxidant effect by blocking the induction of lipid peroxidation, preserving brain energy (ATP) content, and greatly reducing the hypoxic alterations in brain enzymatic and non-enzymatic antioxidants. Histopathological examination of the brain tissue supported these biochemical findings. This study showed that ID and l-arg were capable of reducing neurological injury following HP in rat, and support the idea of the usefulness of l-arg and ID as prophylaxis from hypoxic brain injury.

Neuroprotective effect of carnosine and cyclosporine-A against inflammation, apoptosis, and oxidative brain damage after closed head injury in immature rats.

Abstract Context: Traumatic brain injury in the pediatric population can have a great economic and emotional impact on both the childs family and society. Objective: The present study aimed to compare the effects of carnosine (CAR) and/or cyclosporine A (CyA) on oxidative brain damage after closed head injury (CHI) in immature rats. Materials and methods: Thirty-day-old rat pups were divided into five groups: non-traumatic control group, trauma group underwent CHI, trauma group injected with CAR (200 mg/kg, i.p.) following CHI for 7 d, trauma group injected with CyA (20 mg/kg, i.p.) given 15 min and 24 h after CHI, and trauma group treated with CAR and CyA. At the end of the treatment, rats were sacrificed; blood and brains were collected for assessing different biochemical parameters. Results: Trauma significantly increased brain level of malondialdehyde, nitric oxide, glucose, calcium, inflammatory mediators. Brain DNA damage was confirmed by comet assay and the significant increase in brain caspase-3 activity. Moreover, the serum level of Fas ligand in traumatized animals was significantly elevated. Concomitant decrease in brain-reduced glutathione (GSH) and calcium-adenosine triphosphatase activity was observed in the traumatized-untreated group. Treatment of traumatized animals with CAR and/or CyA ameliorated all the biochemical changes induced by CHI with marked protective effect in the combination group. Discussion and conclusion: CAR and CyA exerted a synergistic neuroprotective effect against CHI through blocking the induction of lipid peroxidation, reducing inflammatory, and oxidative stress biomarkers, preserving brain GSH content, and reducing the alterations in brain apoptotic biomarkers in traumatized animals.CONTEXT Traumatic brain injury in the pediatric population can have a great economic and emotional impact on both the childs family and society. OBJECTIVE The present study aimed to compare the effects of carnosine (CAR) and/or cyclosporine A (CyA) on oxidative brain damage after closed head injury (CHI) in immature rats. MATERIALS AND METHODS Thirty-day-old rat pups were divided into five groups: non-traumatic control group, trauma group underwent CHI, trauma group injected with CAR (200 mg/kg, i.p.) following CHI for 7 d, trauma group injected with CyA (20 mg/kg, i.p.) given 15 min and 24 h after CHI, and trauma group treated with CAR and CyA. At the end of the treatment, rats were sacrificed; blood and brains were collected for assessing different biochemical parameters. RESULTS Trauma significantly increased brain level of malondialdehyde, nitric oxide, glucose, calcium, inflammatory mediators. Brain DNA damage was confirmed by comet assay and the significant increase in brain caspase-3 activity. Moreover, the serum level of Fas ligand in traumatized animals was significantly elevated. Concomitant decrease in brain-reduced glutathione (GSH) and calcium-adenosine triphosphatase activity was observed in the traumatized-untreated group. Treatment of traumatized animals with CAR and/or CyA ameliorated all the biochemical changes induced by CHI with marked protective effect in the combination group. DISCUSSION AND CONCLUSION CAR and CyA exerted a synergistic neuroprotective effect against CHI through blocking the induction of lipid peroxidation, reducing inflammatory, and oxidative stress biomarkers, preserving brain GSH content, and reducing the alterations in brain apoptotic biomarkers in traumatized animals.

New mechanism in the modulation of carbon tetrachloride hepatotoxicity in rats using different natural antioxidants

Abstract Transforming growth factor-β (TGF-β1) enhances the expression of apoptosis induced by certain cytokines and oncogenes. Activation of small mother against decapentaplegic (Smads) by TGF-β results in fibrotic, apoptotic processes. PI-3/AKT focal adhesion kinase-phosphatidylinositol3-kinase (AKT), the mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription-3 (STAT3) pathways are influence in COX-2 and VEGF-stimulating pathways. NF-E2-related factor-2 (Nrf2) is an essential transcription factor that regulates an array of detoxifying and antioxidant defense genes expression in the liver. The objective of this study is to examine whether silymarin alone or in combination with vitamin E and/or curcumin plays a modulatory role against MAPK, STAT3, AKT, Smad-2 and TGF-β protein expressions that produced apoptotic damage in rat’s liver by the administration of carbon tetrachloride (CCl4). The results of the present work revealed that CCl4-induced an elevation of serum alanine aminotransferase (ALT) with concomitant increase in MAPK, STAT3, AKT, Smad-2 and TGF-β hepatic protein expression, administration of silymarin alone down regulates these expressions. Treatment with vitamin E and/or curcumin along with silymarin produced best results in this concern. On the other hand, Nrf2 protein expression was down regulated by CCl4 whereas concurrent treatment with vitamin E and/or curcumin along with silymarin increased this expression. It was concluded that CCl4-induced protein expression of apoptotic and fibenorgenic factors. Whereas administration of silymarin alone or in combination with vitamin E and/or curcumin plays a modulatory role against the previous aforementioned apoptotic factors expressions. The use of vitamin E and/or curcumin potentiates the anti-apoptotic action of silymarin. So this combination can be used as hepatoprotective agent against other hepatotoxic substances.

Effect of vitamin E and α-lipoic acid on nano zinc oxide induced renal cytotoxicity in Rats

, Interleukin-6 (IL-6), C-reactive protein (CRP) and IgG were also elevated in rat serum compared to control normal group. Additionally, blood glucose level, as well as serum urea, and creatinine levels were significantly increased in rats intoxicated with ZnO-NP compared to normal control group. On the other hand, reduced glutathione (GSH) level was decreased in renal tissue. These biochemical findings were supported by the histopathological examination of renal tissue and the hazardous effects were dose dependant. Treatment of rats with Vit E or

Effect of aliskiren and carvedilol on expression of Ca2+/calmodulin-dependent protein kinase II δ-subunit isoforms in cardiac hypertrophy rat model

Abstract Context: The critical role of CaMKIIδ isoforms in cardiac hypertrophy is well documented. Objective: This study was aimed to investigate the possible inhibitory effects of aliskiren (ALS) and/or carvedilol (CAV) on CaMKIIδ isoforms expression in experimental cardiac hypertrophy. Materials and methods: Male Wistar albino rats were subcutaneously injected with isoproterenol (ISO) (5 mg/kg/day) for 4 weeks to induce cardiac hypertrophy. Hypertrophied rats were daily treated with either ALS (10 mg/kg) and/or CAV (10 mg/kg). At the end of the treatment, rats were killed; blood and hearts were collected for assessing different biochemical parameters. Results: ISO treatment significantly increased heart weight to body weight (HW/BW) ratio, serum creatine kinase MB (CK-MB) and troponin T (Tn-T) levels, and plasma renin activity (PRA) as compared to control rats. Additionally, ISO treatment produced a significant increase in the expression of myocardial CaMKIIδ2 and CaMKIIδ3 that were associated with significant elevation in myocardial caspase-3 protein expression. Histopathological examination of rats exposed to ISO treatment showed severe myocardial cell degeneration. ALS and/or CAV treatment significantly reduced the altered HW/BW ratio, serum CK-MB and Tn-T levels, PRA, and caspase-3 protein expression in hypertrophied rats, with maximal improvement in the combination group. These biochemical findings were supported by the histopathological examination of the heart tissue. Additionally, treatment with ALS and CAV significantly inhibited ISO-induced increase in CaMKIIδ2 and CaMKIIδ3 expression levels. Discussion and conclusion: The present study indicated that ALS and CAV treatment ameliorated ISO-induced hypertrophy via inhibiting the expression and the activity of CaMKIIδ isoforms and the associated myocardial apoptosis.