Introduction: Neuronal cell death and glial cell activation are the main pathological findings induced by seizures secondary to oxidative stress. Previous studies have explained neuronal cell death on the basis of cell necrosis and apoptosis. Recent studies have attributed the neuronal loss to autophagy. The proved antioxidant and antifibrotic effect of nilotinib favours its use in the management of epileptic seizures. Aim of the study was to analyse the neuroprotective and antiepileptic effect of nilotinib and explain its mechanism of action. Material and methods: Forty adult male rats were divided into four groups: control, pentylenetetrazol (PTZ) group (injected with PTZ 60 mg/kg, s.c.), pregabalin (Pregb)-PTZ group (pretreated with pregabalin daily 30 mg/kg; orally for 1 week) and nilotinib (NIL)-PTZ group (pretreated with nilotinib, 25 mg/kg daily for 1 week) prior to PTZ. Seizure latency was evaluated, the hippocampus tissue level of antioxidant enzymes was assessed. The histopathological changes in the hippocampus were studied using hematoxylin and eosin stain and immunohistochemical stain for brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), beclin-1, nuclear factor kappa-B (NF-κB) and Bcl-2-like protein 4 (BAX). Results: Nilotinib induced an increase in the latency of seizures, enhanced the antioxidant levels of the γ-aminobutyric acid and nuclear factor (erythroid-derived 2)-like 2 activities together with the improvement of the hippocampal histology. A reduction was reported for BDNF, GFAP, beclin-1, NF-κB and BAX expression in nerve cells. Conclusions: Nilotinib may have promising neuroprotective and antiepileptic effects against pentylenetetrazolinduced seizures through promoting the antioxidant, antifibrotic, anti-inflammatory, antiapoptotic pathways and inhibiting autophagy.

Nephrotoxicity is a dose-limiting side effect of cisplatin (CSP). The study investigated the possible protective role of trimetazidine (TMZ) against CSP-induced nephrotoxicity in rats. Rats were divided into 4 groups; control Group, TMZ Group, CSP Group, and CSP + TMZ Group. CSP group showed significant deterioration in kidney function with structural changes in the form of interstitial hemorrhage glomeruli shrinkage and peritublar capillary congestion, tubular cells vacuolation, pyknosis, shedding and necrosis and inflammatory cell infiltrates; all indicating renal damage. CSP also caused a significant increase in the lipid peroxidation marker malondialdehyde levels (MDA), renal NF-κB (nuclear factor-kappa B) DNA-binding activity and protein expression, tumor necrosis factor-alpha (TNF-α) and IL-6 levels.Treatment with TMZ before and after CSP injection produced significant improvement of kidney function and histopathology. TMZ treatment also significantly attenuated CSP-induced oxidative stress and suppressed elevated levels of TNF-α and IL-6, NFκB expression and its DNA-binding activity caused by CSP administration.TMZ has protective effect against CSP-induced nephrotoxicity mediated by reduction of oxidative stress, and attenuation of CSP-induced inflammation.Keywords: Cisplatin, Oxidative stress, Trimetazidine, nephrotoxicity, NF-κB IntroductionTMZ, a piperazine derivative, is the first of a new class of metabolic agents. It has been found to have a cytoprotective effect on both renal and hepatic cells (Cristina et al. 2013). TMZ is well known for its cardioprotective effect and is used as adjuvant anti-anginal drug. It can normalize metabolic disturbances in low-flow myocardial ischemia and prevents the secondary cell death that may follow (Kantor et al. 2000; Sellier and Broustet 2003). TMZ acts by preserving intracellular levels of ATP through shifting cardiac metabolism from fatty acid oxidation to more glucose oxidation (Kantor et al. 2000). The drug may also reduce free-radical-mediated injury (Kaur et al. 2003), inhibit cell apoptosis (Khan et al. 2010) and improve endothelial function (Park et al. 2010).Cis-Diammineplatinum (II) dichloride (CSP) is the prototype of the platinum containing anti-cancer drugs. It's widely used in clinical practice as part of the standard treatment plans for various solid tumors (Oh et al. 2014). CSP adverse effects include ototoxicity, bone marrow suppression and hepatotoxicity but the main dose- The current study was undertaken to investigate the possible protective role of TMZ against CSP-induced renal damage in rats and to elucidate the possible underlying mechanism. Materials and methods MaterialsCisplatin (Bristol-Myers-Squibb Co.) was obtained as the pharmaceutical drug (5 mg/mL vial) and was diluted with isotonic saline. Trimetazidine dihydrochloride; Experimental protocolTwenty four rats were divided randomly into four groups with six rats for each group. received TMZ (20 mg/kg/day, p.o.) for ten consecutive days, Group III: received drug vehicle ...

Tobacco smoking with its various forms is a global problem with proved hazardous effects to human health. The present work was planned to study the defending role of agmatine (AGM) on hepatic oxidative stress and damage induced by nicotine in rats. Thirty-two rats divided into four groups were employed: control group, nicotine-only group, AGM group, and AGM-nicotine group. Measurements of serum hepatic biochemical markers, lipid profile, and vascular cell adhesion molecule-1 were done. In addition, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) activity, and nitrate/nitrite (NOx) levels were estimated in the liver homogenates. Immunohistochemistry for Bax and transforming growth factor beta (TGF-β1) and histopathology of the liver were also included. Data of the study demonstrated that nicotine administration exhibited marked liver deterioration, an increase in liver enzymes, changes in lipid profile, and an elevation in MDA with a decline in levels of SOD, GSH, and NOx (nitrate/nitrite). Also, levels of proapoptotic Bax and profibrotic TGF-β1 showed marked elevation in the liver. AGM treatment to rats in nicotine-only group ameliorated all the previous changes. These findings indicate that AGM could successfully overcome the nicotine-evoked hepatic oxidative stress and tissue injury, apoptosis, and fibrosis.

Introduction. Sexual dysfunction and infertility are symptoms which have been rarely studied in patients treated with antischizophrenic drugs, aripiprazole and olanzapine, for long period. This work aimed to investigate the effects of aripiprazole and olanzapine on the structure of seminiferous tubules of rats at both light microscopic and ultrastructural levels. Material and methods. Sixty adult male rats were divided into 3 groups (n = 20): control group (Group I) and two experimental ones (II and III). Rats in Group II received 2 mg/kg/day aripiprazole while rats in Group III received 0.5 mg/kg/day olanzapine for 14 weeks. Thereafter, testis were removed and processed for both light and electron microscopic study. Qualitative morphological analyses and histomorphometric measurements of seminiferous tubules were performed. Results. Rats in Group II showed reduction of testicular weight, seminiferous tubules' diameter, epithelial height, spermatogenic count, spermatogenic index and spermatogenic score whereas Sertoli cells count was increased. Olanzapine-treated rats also showed epithelial desquamation, separation and apoptotic changes of germ cells. Sertoli cells showed vacuolization, dilatation of smooth endoplasmic reticulum and accumulation of lipid droplets. Abnormality in the shape and structure of late spermatids and presence of giant cells were also demonstrated. Aripiprazole induced less adverse histological changes in rat testis than olanzapine. Conclusions. Olanzapine followed by aripiprazole had adverse histological effects on the structure of the seminiferous tubules, which may affect spermatogenesis.

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Nicotine mediates some of the injurious effects caused by consuming tobacco products. This work aimed at investigating the defensive role of alpha-lipoic acid (ALA) with its known antioxidant and antiinflammatory effect in nicotine-induced lung and liver damage. Rats were arranged into 4 groups: control, nicotine, ALA, and ALA-nicotine groups. Oxidative stress and antioxidant status were determined by assessing thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), and glutathione (GSH) levels in lung and liver. Liver enzymes and lipid profiles were measured and pulmonary and hepatic damage were assessed by histopathological examination. Also, serum levels of transforming growth factor beta 1 (TGF-β1) and vascular cell adhesion molecule 1 (VCAM-1) were determined. The results revealed an increase in TBARS in tissues and a reduction in both SOD and GSH activity in the nicotine-treated rats. Nicotine induced high levels of liver enzymes, TGF-β1, VCAM-1, and dyslipidemia with histopathological changes in the lung and liver. ALA administration along with nicotine attenuated oxidative stress and normalized the SOD and GSH levels, ameliorated dyslipidemia, and improved TGF-β1 and VCAM-1 with better histopathology of the lung and liver. The study data revealed that ALA may be beneficial in alleviating nicotine-induced oxidative stress, dyslipidemia, and both lung and liver damage.

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Introduction: Skeletal muscle injuries comprise the greater part of sports-related injuries. Role of growth factors in healing of injured tissue encouraged the use of platelet-rich plasma (PRP). Aim of the work: We aimed to study the effect of PRP on skeletal muscle injury. Materials & Methods: Forty adult male rats were divided into four equal groups; control and 2, 7, 14 days after the injury. The injured muscles were either treated with PRP or left without treatment. The rats were sacrificed and the muscle specimens were processed for histological and immunohistochemical staining for detection of Anti-MyoD, anti-CD34 and anti TGFβ1 followed by morphometric study. Results: PRP treatment induced initial intense inflammatory response with neutrophils and macrophages cell infiltrate subsided in the 7th day. When compared to untreated groups, PRP treated ones showed significant increases in the mean number of regenerating muscle fibers (22.03±4.08) and angiogenesis (10.83±2.46) on the 7th day. The median number of MyoD immunopositive stellate cells showed a significant increase on the 2nd day ,72 (62-78) and then decrease on the 7th day; 28(22-33) to be non significant after 14th days; 4(3-5) of injury. A significant decrease in the mean area % of collagen deposition (2.27±.0.59, 3.68±0.72 and 4.76±0.82) and TGF β1 immunoexpression, medians; 5 (4.20-5.70), 2.50 (2.10-3.50) and 2.30( 1.60-3.20) after 2, 7 and 14 days, respectively, were observed. Conclusions: PRP could exert a promising effect on skeletal muscle injuries via enhancing myogenesis, neovascularization and reduction of fibrosis. Since autologous blood preparations are safe, PRP may serve as a valuable adjunct in management of such injuries.