Protective effects of evening primrose oil on behavioral activities, nigral microglia and histopathological changes in a rat model of rotenone-induced parkinsonism.

Parkinson's disease (PD) is a neurodegenerative illness described as damage to dopaminergic neurons. There is increasing evidence that neuroinflammatory activity mediated by microglia is extensively involved in the initiation and development of PD. This study assessed the protective effect of evening primrose oil [EPO] as an anti-inflammatory mediator in rotenone-induced Parkinsonism in rats. Forty-eight adult male albino rats were distributed into four groups. Group I: control. Group II: rotenone [1.5 mg/kg/48 h] was administered subcutaneously to the rats. Groups III and IV: the rats had rotenone plus daily oral [EPO] 5 and 10 mg/kg respectively. After 24 days, motor behaviour was assessed by the open field and rotarod tests. The brain striata were isolated and tested for tumor necrosis factor (TNF)-α, interleukin 6, NF-B [nuclear factor-kappa B], and dopamine levels. The mid-brain tissues were processed for light and electron microscopy examinations, and immunohistochemical staining for tyrosine hydroxylase [TH], and microglia cells' markers: [CD68 and IBA1]. Results revealed that rotenone-treated rats had poor motor function, a significantly increased striatal level of inflammatory markers, markedly shrunken neurons, degeneration, pyknotic neuroglia, neuropil vacuolation, markedly destructed swollen mitochondria with loss of their cristae, and dilated rough endoplasmic reticulum, as well as decreased TH and increased CD68 and IBA1-positive cells. Treatment with EPO ameliorates all the neuropathological changes of rotenone in the rat brain. In conclusion, EPO enhanced the motor performance, reduced the inflammatory marker levels, restored dopamine levels, and ameliorated the neurohistopathological lesions of rats with experimental parkinsonism, suggesting its neuroprotective and anti-inflammatory effects.

Combined Treatment of Adipose Derived-Mesenchymal Stem Cells and Pregabalin Is Superior to Monotherapy for the Treatment of Neuropathic Pain in Rats.

AIMS: Neuropathic pain following nerve injury does not respond well to most available pharmacological remedies. We aimed to compare the outcome of the addition of adipose-derived mesenchymal stem cells (ADMSCs) to pregabalin for neuropathic pain treatment. METHODS: Adult female albino rats (n = 100) were randomized to receive traumatic sciatic nerve injury or sham. Animals were then randomized to ADMSC treatment with or without pregabalin. We conducted a battery of neurobehavioral and electrophysiological to assess neuropathic pain. Following sacrifice, we evaluated the histological changes and gene expression of brain-derived neurotrophic factor (BDNF) in the sciatic nerve. Serum and sciatic nerve tissue pro- and inflammatory cytokine levels were also assessed. RESULTS: (1) All treatments significantly improved thermal withdrawal latency, sciatic nerve conduction velocity, and proinflammatory cytokine levels in injured animals, with no significant effect of the combined treatments compared to pregabalin monotherapy (p < 0.05 each). (2) Combined treatment significantly improved medial gastrocnemius electromyographic amplitude and sciatic function index compared to pregabalin monotherapy (p < 0.05 each). (3) Combined treatment significantly increased the BDNF expression, decreased anti-inflammatory cytokine (p < 0.05 each), and restored the structural nerve damage, compared to pregabalin monotherapy. CONCLUSIONS: Combined treatment is associated with greater improvement of the sciatic nerve structure and function. Further studies are warranted to study the mechanism of action of the combined treatment to improve neuropathic pain.

Celecoxib aggravates cardiac apoptosis in L-NAME-induced pressure overload model in rats: Immunohistochemical determination of cardiac caspase-3, Mcl-1, Bax and Bcl-2.

The mechanism of celecoxib cardiovascular adverse events was earlier investigated; yet in-depth investigations are needed to assess the involvement of its pro-apoptotic effect throughout this process. An in-vivo chronic rat model of pressure overload employing NÊ·-nitro-l-arginine methyl ester (L-NAME) was tested at different time intervals to ensure the occurrence of persistent myocardial apoptosis along with pressure overload. Seven groups of male Wistar rats were assigned as (i) distilled water; (ii-iv) L-NAME (60 mg/kg) for 6, 12 or 16 weeks; (v-vii) L-NAME [16 weeks] + celecoxib (25, 50 or 100 mg/kg), from week 13 to week 16. Treatment with L-NAME for 6, 12 or 16 weeks increased systolic blood pressure, serum level of creatine kinase-MB and lactate dehydrogenase. Further, it induced cardiac hypertrophy, detected in terms of greater heart weight index and cardiomyocyte cross-sectional area and produced interstitial and perivascular fibrosis. Moreover, administration of L-NAME increased cardiac immunostaining for activated caspase-3 and Bax/Bcl-2 ratio whereas; immunostaining for Mcl-1 was decreased. Administration of celecoxib (25, 50 or 100 mg/kg) aggravated the L-NAME-induced toxicity. The work results shed the light on the putative pro-apoptotic effect of celecoxib at a risk state of pressure overload comparable to the clinical condition of essential hypertension.

Evening primrose oil or forskolin ameliorates celecoxib-enhanced upregulation of tissue factor expression in mice subjected to lipopolysaccharide-induced endotoxemia.

Celecoxib, a selective cyclooxygenase-2 inhibitor, produces thrombotic events in patients predisposed to cardiovascular risk factors. One theory reported an increase in endothelial expression of tissue factor (TF) as a predisposing factor. This work explored the effect of evening primrose oil (EPO), a source of prostaglandin E1, and forskolin (a cyclic adenosine monophosphate stimulator) against the prothrombotic effect of celecoxib in mice. Lipopolysaccharide mouse model of endotoxemia was used to induce an upregulation of TF activity. Male mice received celecoxib (25 mg/kg), celecoxib plus EPO, or celecoxib plus forskolin for 4 weeks and then subjected to a prothrombotic challenge in the form of an intraperitoneal injection of lipopolysaccharide. Results showed an increase in plasma TF activity, endothelial TF expression, and thrombin-antithrombin (TAT) but lower antithrombin III (ATIII) level in mice that received celecoxib in comparison to those that received the vehicle. Adding EPO or forskolin to celecoxib regimen significantly decreased the prothrombotic effect of celecoxib. A positive correlation (r = 0.8501) was found between TF activity and TAT. Co-administration of EPO or forskolin decreased the activity of TF and mitigated the prothrombotic effect of celecoxib. Therefore, these combinations may have the utility to abrogate the prothrombotic adverse effect of celecoxib in clinical setting.