This study was designed to test the effects of intracerebroventricularly (i.c.v.) administered CDP-choline (cytidine-5'-diphosphate-choline; citicoline) and its metabolites in rat models of inflammatory and neuropathic pain. The i.c.v. administration of CDP-choline (0.5, 1.0 and 2.0 µmol) produced a dose and time-dependent reversal of mechanical hyperalgesia in both carrageenan-induced inflammatory and chronic constriction injury-induced neuropathic pain models in rats. The antihyperalgesic effect of CDP-choline was similar to that observed with an equimolar dose of choline (1 µmol). The CDP-choline-induced antihyperalgesic effect was prevented by central administration of the neuronal high-affinity choline uptake inhibitor hemicholinium-3 (1 µg), the nonselective nicotinic receptor antagonist mecamylamine (50 µg), the α7-selective nicotinic ACh receptor antagonist, α-bungarotoxin (2 µg) and the γ-aminobutyric acid B receptor antagonist CGP-35348 (20 µg). In contrast, i.c.v. pretreatment with the nonselective opioid receptor antagonist naloxone (10 µg) only prevented the CDP-choline-induced antihyperalgesic effect in the neuropathic pain model while the nonselective muscarinic receptor antagonist atropine (10 µg) did not alter the antihyperalgesic effect in the two models. These results indicate that CDP-choline-elicited antihyperalgesic effect in different models of pain occurs through mechanisms that seem to involve an interaction with supraspinal α7-selective nicotinic ACh receptors, and γ-aminobutyric acid B receptors, whereas central opioid receptors have a role only in the neuropathic pain model.
Oxidative stress has been involved in the aging process and the pathogenesis of type-2 diabetes, which is a serious health problem worldwide. This study investigates the anti-aging, anti-apoptotic, and antioxidant properties of alpha-lipoic acid (ALA), aiming to improve aged rat pancreatic cells. In this regard, half maximal effective concentration (EC) of ALA based on the survival of aged pancreatic islet cells was determined as 100 µM. Following this, p38 and p53 genes expression as key factors in aging, oxidative stress biomarkers, insulin secretion, and Pdx1 protein expression were evaluated using real-time PCR, ELISA reader, and fluorescence microscope. It was revealed that ALA reduces and controls the effects of aging on beta cells mainly by suppressing p38 and p53 at the gene level (P < 0.001 and P < 0.01), respectively, reducing reactive oxygen species (P < 0.001) and enhancing levels of thiols (P < 0.05) compared with the aged islets. Furthermore, both qualitative and quantitative investigations of insulin secretion have shown that ALA can improve aged cells' function and increase insulin secretion specially in the stimulating concentration of glucose. Also, the expression of Pdx1 was considerably increased by ALA in comparison to the aged pancreatic islets (P < 0.001). As far as the authors of the present study are concerned, this is the first study, which evaluated aging associated with p38 and p53 pathways, oxidative stress parameters, and the expression of insulin in beta cells of an aged rat and reaffirmed the fact that ALA has a significant antioxidant role in reducing the aging process.
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