Azza M. Mohamed

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.

Pulmonary prophylactic impact of melatonin and/or quercetin: A novel therapy for inflammatory hypoxic stress in rats

Abstract The study aims to compare, through histological and biochemical studies, the effects of quercetin, melatonin and their combination in regulation of immuno-inflammatory mediators and heat shock protein expressions in sodium nitrite induced hypoxia in rat lungs. The results revealed that NaNO2 injection caused a significant decrease in Hb in rats, while serum levels of TNF-α, IL-6 and CRP, VEGF and HSP70 were elevated compared to the control group. Administration of melatonin, quercetin or their combination before NaNO2 injection markedly reduced these parameters. Histopathological examination of the lung tissue supported these biochemical findings. The study suggests that melatonin and/or quercetin are responsible for lung tissue protection in hypoxia by downregulation of immuno-inflammatory mediators and heat shock protein expressions. Pre-treatment of hypoxic animals with a combination of melatonin and quercetin was effective in modulating most of the studied parameters to near-normal levels.

Regulating Effect Of Carnosine And /Or L- Arginine On The Expression Of Inflammatory Molecules Induced Nephropathy In The Hypoxic Rat Model

This study aimed to explore the effective role of carnosine and /or L- arginine in down regulation of the inflammatory molecule expression caused renal damage in response to sodium nitrite (NaNO2) induced hypoxia in rats . NaNO2 was administered subcutaneously (s.c.) to rats as a single dose (60 mg/kg body weight ). L-arginine (200mg/Kg body weight) and carnosine (250 mg/ Kg body weight ) were administered (i.p.) as a single dose , 24 h before NaNO2 injection. The results revealed that pre- administration of arginine and /or carnosine to NaNO2 hypoxic rats, significantly modulated the increases in serum markers of renal function (creatinine and urea) as well as the decrease in hemoglobin (Hb) level versus hypoxic rats. The two agents each alone or in a combination, markedly down regulated the serum pro-inflammatory molecules, including tumor necrosis factor-α (TNF- α) , C-reactive protein (CRP), vascular endothelial growth factor (VEGF) and heat shock protein -70 (HSP-70) as well as interleukin-6 (IL-6) in renal tissue compared to NaNO2 hypoxic rats . Also, the two agents successfully down modulated the alteration in the serum hypoxia inducible factor 1α (HIF 1α) . The present biochemical results were also supported by histopathological examination. In conclusion, the current data revealed that although the efficacy of arginine or carnosine each alone, their combination was more effective in ameliorating the renal damage induced by inflammatory molecules in response to NaNO2 hypoxia . This may support the use of this combination as an effective drug to treat hypoxic renal damage

Role of Carnosine and Melatonin in Ameliorating Cardiotoxicity of Titanium Dioxide Nanoparticles in the Rats

The aim of this work was to study the possible cardiotoxicity of two different doses of 50 nm nano titanium dioxide (n-TiO2) and the possible modulating effects of the use of two natural antioxidants carnosine and melatonin. The results showed that TiO2- NPs produced deleterious effects on rat cardiac tissue as confirmed by the increased levels of serum myoglobin, troponin-T and CK-MB. Increased levels of serum Inflammatory markers represented by the tumor necrosis factor alpha (TNF-α) and Interleukin-6 (IL-6) was also noticed. Caspase3 and IGg were elevated compared to the control group in a dose dependant manner. treatment of the rats with Carnosine or melatonin. along with TiO2- NPs administration significantly improved most of the elevated biochemical markers. It was concluded that the use of Carnosine or melatonin could play a beneficial role against deleterious effects of TiO2- NPs

Assessment of the Potential Role of Silymarin Alone or in Combination with Vitamin E and/ or Curcumin on the Carbon Tetrachloride Induced Liver Injury in Rat

The aim of this study was to investigate the effective role of silymarin either alone or in a combination with vitamin E and/or curcumin against the toxic impact of carbon tetrachloride (CCl4) induced liver injury The results revealed that administration of silymarin alone or in a combination with vitamin E and/or curcumin for 21 consecutive days, 24 h after CCl4 injection to rats, markedly ameliorated DNA damaged and apoptosis markers in rat livers, proinflammatory markers including tumor necrosis factor- α (TNF- α) and C-reactive protein (CRP ) in rat livers as well as interleukin 6 (IL-6), interferon gamma (IFN-γ) and vascular endothelial growth factor (VEGF) in rat sera. These treatments also could ameliorated the alteration in cytochrome P450 2E1 (CYP2E1) activity in livers of CCl4 intoxicated rats as well as the increase in the serum alanine aminotransferase (ALT) compared with CCl4 intoxicated untreated rats. The present biochemical results are supported by histo-pathological examination. In conclusion, silymarin in a combination with vitamin E and curcumin was the most effective treatment in alleviating CCl4 induced liver damage and this may support the use of this combination as an effective treatment against liver damage induced by toxic agents.

Prophylactic administration of carnosine and melatonin abates the incidence of renal toxicity induced by an over dose of titanium dioxide nanoparticles

The alleviative effects of two antioxidants, carnosine (Car) and melatonin (Mel), against titanium dioxide nanoparticles (TiO2‐NPs) toxicity‐induced oxidative and inflammatory renal damage were examined in rats. Administration of these antioxidants along with TiO2‐NPs effectively reduced serum urea, uric acid, creatinine, glucose, tumor necrosis factor‐α, interleukin‐6, C‐reactive protein, immunoglobulin G, vascular endothelial growth factor, and nitric oxide, as well as a significant amelioration of the decrease in glutathione levels in renal tissue was observed, compared to those in rats treated with TiO2‐NPs alone. The renoprotective properties of the antioxidants were confirmed by reduced intensity of renal damage as demonstrated by histological findings. In conclusion, Car and Mel play protective roles against TiO2‐NPs‐induced renal inflammation and oxidative injury, likely due to their antioxidant and anti‐inflammatory properties.