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The current study was conducted to investigate the possible ameliorative role of zinc nanoparticles (Zn NPs) against silver nanoparticles (Ag NPs)-induced oxidative and apoptotic brain damage in adult male rats. Twenty-four mature Wistar rats were randomly and equally divided into four groups: control group, Ag NPs group, Zn NPs group, and Ag NPs + Zn NPs group. Rats were exposed to Ag NPs (50 mg/kg) and/or Zn NPs (30 mg/kg) daily by oral gavage for 12 weeks. The results revealed that exposure to Ag NPs significantly increased malondialdehyde (MDA) content, decreased catalase and reduced glutathione (GSH) activities, downregulated the relative mRNA expression of antioxidant-related genes (Nrf-2 and SOD), and upregulated the relative mRNA expression of apoptosis-related genes (Bax, caspase 3 and caspase 9) in the brain tissue. Furthermore, severe neuropathological lesions with a substantial increase in the caspase 3 and glial fibrillary acidic protein (GFAP) immunoreactivity were observed in the cerebrum and cerebellum of Ag NPs-exposed rats. Conversely, co-administration of Zn NPs with Ag NPs significantly ameliorated most of these neurotoxic effects. Collectively, Zn NPs can be used as a potent prophylactic agent against Ag NPs-induced oxidative and apoptotic neural damage., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Several antidepressants have been used to treat severe pain in clinics. Recently, we reported that the centrally acting non-narcotic antitussive (cough suppressant drug), tipepidine produces an antidepressant-like effect in the forced swimming test, although the mechanism of action appears to be quite different from that of known antidepressants. In the present study, we investigated whether a combination of tipepidine and carbamazepine acts synergistically to induce an antinociceptive effect in the acetic acid-induced writhing test in mice. Prior to studying the combination of tipepidine and carbamazepine, the analgesic action of tipepidine alone was also examined in mice. Tipepidine at 5-40mg/kg i.p. significantly reduced the number of writhes induced by acetic acid in mice. Carbamazepine at 20mg/kg i.p. also significantly reduced the writhing reaction. Furthermore, co-administration of carbamazepine (5 and 10mg/kg, i.p.) and tipepidine (2.5mg/kg i.p.) significantly decreased the number of writhes induced by acetic acid. This finding suggests that a combination of carbamazepine and tipepidine may be a new strategy for the treatment of neuropathic pain such as what occurs in trigeminal neuralgia, because the use of carbamazepine is often limited by its adverse effects and by reduction of its analgesic efficacy by microsomal enzyme induction., (Copyright © 2010 Elsevier B.V. All rights reserved.)