Lobna Abdelzaher

Background: Pregabalin (PGB) was approved as new anti-epileptic drugs with little information about its teratogenic effect. Aim of the work: to evaluate the developmental toxicity of PGB. Materials and methods: 60 pregnant albino rats were divided into three groups. PGB (500 mg/kg body weight/day) was given to group II, PGB (1250 mg/kg body weight/day) was given to Group III and no medications were given to group I. The pups were normally delivered. Liver, kidney and heart specimens were prepared for histological, immunohistochemical, and morphometric studies. Results: A dose of 500 mg of PGB had minimal toxic effects in the form of mild collagen deposition and moderate positive caspase-3 immunoexpression. PGB dose of 1250 mg/kg induced gross toxic effects in form of degenerated cardiac myofibres, ruptured blood vessels, vacuolations in the renal cortex, fibrosis and strong positive caspase-3 immunoexpression. Conclusion: PGB at dose of 500 mg/kg revealed minimal toxic changes. PGB cause embryotoxicity in a dose-dependent manner, as the higher dose induced more degenerative changes.

Sepsis is a systemic inflammatory response syndrome (SIRS) that occurs when the body's immunity overreacts to an infection. It is followed by life-threatening medical consequences, including multiple organ failure (MOD). Dexmedetomidine (DEX) is a selective 2 adrenergic agonist that is used as a short-term sedative in the ICU. Apart from improving sepsis prognosis, it is believed to have an organ protecting function. Our study aimed at confirming DEX ameliorative role in sepsis-induced organ damage. We also studied DEX mitigating effect on sepsis-induced acute lung injury (ALI) and elucidated the possible mechanism. Thirty rats were randomly assigned into three groups (n=10): sham, cecal ligation and puncture (CLP)-induced sepsis, or DEX-treated CLP (DEX + CLP). 15 minutes before the CLP procedure, a prophylactic dosage of DEX (5g/kg) was given intraperitoneally (IP). Animals were slaughtered 48 hours after the surgery was completed. Histological examination for tissue samples from lung, liver and kidney. CD54 expression in lung tissue was also investigated. Blood was also taken for hematological analysis. CLP rats showed different pathological lesions in lung, kidney and liver. We reported severe pulmonary tissue damage in CLP group accompanied with enhanced CD54 expression. DEX decreased the severity of histopathological changes in the affected organs and reduced the expression of CD54 in the lung tissue as well. However, DEX could not improve sepsis-induced hematological impairment. DEX attenuated sepsis through decreased CD54 expression in the lung as well as its hepato-renal protective effect in the CLP model.

Neuroinflammation plays a crucial role in Alzheimer's disease (AD) pathogenesis. Apoptosis, along with impaired neurogenesis, has been linked to AD neurodegenerative cell death, likely due to overexpression of cyclooxygenase-2 (COX-2). We investigated whether the concurrent administration of celecoxib, a selective COX-2 inhibitor, with rivastigmine, the standard anti-Alzheimer, would enhance rivastigmine anti-Alzheimer activity in the aluminum chloride (AlCl3) Alzheimer's rat model. Male rats were randomly assembled into control (Cont), AlCl3-treated (Al), rivastigmine-treated (RIVA), celecoxib-treated (Celeco), and combined rivastigmine and celecoxib-treated (RIVA+Celeco) groups. They were studied for memory, and cognitive skills, along with evaluating hippocampal acetylcholinesterase (AChE) activity. Hippocampal neuropathology, besides apoptosis, astroglial injury, and neurogenesis, were assessed through examining the expression of their related protein markers; activated caspase-3, glial fibrillary acidic protein (GFAP), and nestin. Celecoxib, rivastigmine, and their combination attenuated AlCl3-induced intellectual impairment and the associated neurodegenerative changes. However, the combination therapy had no additional neuroprotective advantage over rivastigmine alone, except for the enhancement of neurogenesis and suppression of apoptosis in the AL-intoxicated rats. As compared to rivastigmine, the efficacy of celecoxib in combination with rivastigmine confers neuroprotection only at the cellular level, enhancement of neurogenesis, and suppression of apoptosis, without having a mitigating effect on Al-induced cognitive impairment.

Objective: Endometriosis is a chronic debilitating inflammatory condition characterized by the presence of endometrial tissues outside the uterine cavity. Pelvic soreness and infertility are the usual association. Due to the poor effectiveness of the hormone therapy and the high incidence of recurrence following surgical excision, there is no single effective option for management of endometriosis. Mesenchymal stem cells (MSCs) are multipotent stromal cells studied for their broad immunoregulatory and anti-inflammatory properties; however, their efficiency in endometriosis cases is still a controversial issue. Our study aim was to evaluate whether adipose tissue-derived MSCs (AD-MSCs) could help with endometriosis through their studied anti-inflammatory role. Methods: Female Wistar rats weighting 180 to 250 g were randomly divided into two groups: group 1, endometriosis group; established by transplanting autologous uterine tissue into rats’ peritoneal cavities and group 2, stem cell treated group; treated with AD-MSCs on the 5th day after induction of endometriosis. The proliferative activity of the endometriosis lesions was evaluated through Ki67 staining. Quantitative estimation of interferon γ, tumor necrosis factor-α, interleukin (IL)-6, IL-1β, IL-10, and transforming growth factor β expression, as well as immunohistochemical detection of CD68 positive macrophages, were used to assess the inflammatory status. Results: The size and proliferative activity of endometriosis lesions were significantly reduced in the stem cell treated group. Stem cells efficiently mitigated endometriosis associated chronic inflammatory reactions estimated through reduction of CD68 positive macrophages and the expression of the proinflammatory cytokines. Conclusion: Stem cell therapy can be considered a novel remedy in endometriosis possibly through its anti-inflammatory and antiproliferative properties.

Alzheimer’s disease (AD) is one of the leading causes of dependence and disability among the elderly worldwide. The traditional anti-Alzheimer medication, rivastigmine, one of the cholinesterase inhibitors (ChEIs), fails to achieve a definitive cure. Neuroinflammation plays a central role in AD pathogenesis. We tested the hypothesis that naproxen, a non-steroidal anti-inflammatory drug (NSAID), administration to the rivastigmine-treated aluminum chloride (AlCl3), Alzheimer's rat model, could provide an additive neuroprotective effect compared to rivastigmine alone. The studied groups were control (Cont), AlCl₃ treated (Al), rivastigmine treated (RIVA), naproxen treated (Napro), and combined rivastigmine and naproxen treated (RIVA + Napro). Rats’ memory, spatial learning, and cognitive behavior were assessed followed by evaluation of hippocampal acetylcholinesterase (AChE) activity. Hippocampal and cerebellar histopathology were thoroughly examined. A marker of astroglial injury; glial fibrillary acidic protein (GFAP), the apoptosis maker; activated caspase-3 and the neuroepithelial stem cells marker; nestin expressions were immunohistochemically assayed. AD rats displayed significantly impaired memory and cognitive function, augmented hippocampal AChE activity, massive neurodegeneration associated with enhanced astrogliosis, apoptosis, and impaired neurogenesis. Rivastigmine, naproxen, and their combination decreased hippocampal AChE activity, mitigated behavioral and neuropathological changes in Al-intoxicated rats, possibly through downregulation of activated caspase-3 and upregulation of nestin. Except for the enhancement of neurogenesis and suppression of apoptosis, the combination therapy had no additional neuroprotective benefit over rivastigmine-only therapy. Naproxen's efficacy was demonstrated by its ability to act at the cellular level, enhance neurogenesis, and suppress apoptosis without having an additional mitigating impact in Al-induced cognitive impairment.

Background and Aim Thimerosal (THIM) is a mercury-containing preservative widely used in many biological and medical products including many vaccines. It has been accused of being a possible etiological factor for some neurodevelopmental disorders such as autistic spectrum disorders (ASDs). In our study, the potential therapeutic effect of montelukast, a leukotriene receptor antagonist used to treat seasonal allergies and asthma, on THIM mice model (ASDs model) was examined. Methodology Newborn mice were randomly distributed into three groups: (Group 1) Control (Cont.) group received saline injections. (Group 2) THIM-treated (THIM) group received THIM intramuscular (IM) at a dose of 3000 μg Hg/kg on postnatal days 7, 9, 11, and 15. (Group 3) Montelukast-treated (Monte) group received THIM followed by montelukast sodium (10 mg/kg/day) intraperitoneal (IP) for 3 weeks. Mice were evaluated for growth development, social interactions, anxiety, locomotor activity, and cognitive function. Brain histopathology, alpha 7 nicotinic acetylcholine receptors (α7nAChRs), nuclear factor kappa B p65 (NF-κB p65), apoptotic factor (Bax), and brain injury markers were evaluated as well. Results THIIM significantly impaired social activity and growth development. Montelukast mitigated THIM-induced social deficit probably through α7nAChRs upregulation, NF-κB p65, Bax, and brain injury markers downregulation, thus suppressing THIM-induced neuronal toxicity and inflammation. Conclusion Neonatal exposure to THIM can induce growth retardation and abnormal social interactions similar to those observed in ASDs. Some of these abnormalities could be ameliorated by montelukast via upregulation of α7nAChRs that inhibited NF-κB activation and significant suppression of neuronal injury and the associated apoptosis.