The central histaminergic actions are mediated by H1, H2, H3 and H4 receptors. The histamine H3 receptor regulates the release of histamine and a number of other neurotransmitters and thereby plays a role in cognitive and homeostatic processes. Elevated histamine levels suppress seizure activities and appear to confer neuroprotection. The H3 receptors have a number of enigmatic features like constitutive activity, interspecies variation, distinct ligand binding affinities and differential distribution of prototypic splice variants in the CNS. Furthermore, this Gi/Go‐protein‐coupled receptor modulates several intracellular signalling pathways whose involvement in epilepsy and neurotoxicity are yet to be ascertained and hence represent an attractive target in the search for new anti‐epileptogenic drugs. So far, H3 receptor antagonists/inverse agonists have garnered a great deal of interest in view of their promising therapeutic properties in various CNS disorders including epilepsy and related neurotoxicity. However, a number of experiments have yielded opposing effects. This article reviews recent works that have provided evidence for diverse mechanisms of antiepileptic and neuroprotective effects that were observed in various experimental models both in vitro and in vivo. The likely reasons for the apparent disparities arising from the literature are also discussed with the aim of establishing a more reliable basis for the future use of H3 receptor antagonists, thus improving their utility in epilepsy and associated neurotoxicity.

No abstract

No abstract

No abstract

Context: Doxorubicin (Dox) is one of the most active chemotherapeutic agents used to treat various types of cancers. Its clinical utility is compromised due to fatal cardiac toxicity characterized by an irreversible cardiomyopathy. Objective: This study evaluates the cardioprotective potential of naringin (NR) against Dox-induced acute cardiac toxicity in rats. Materials and methods: Male Wistar rats were randomly divided into five groups. NR (50 and 100 mg/kg) was administered intraperitoneally (i.p.) daily from 0 to 14 d. Doxorubicin (15 mg/kg, i.p.) was given as a single dose on the 10th day. On the 14th day, all animals were sacrificed and oxidative stress parameters that include malondialdehyde (MDA), glutathione (GSH) level, superoxide dismutase (SOD), catalase (CAT) activities, and all mitochondrial complexes (I-IV) activities were evaluated along with histopathological studies of the heart. Results: Doxorubicin-induced cardiotoxicity was confirmed by increased (p50.05) MDA, decreased (p50.05) GSH levels, SOD, and CAT activities, mitochondrial complexes (I-IV) activities in the heart tissue. NR (100 mg/kg) showed cardioprotection as evident from significant decreased MDA (p50.001) level, raised (p50.001) GSH level, SOD and CAT activities and increased mitochondrial complexes I (p50.01), II (p50.001), III (p50.001), and IV (p50.05) activities. Further, Dox-induced cardiotoxicity was confirmed by histopathological studies. These obtained results indicated the protective role of NR against Dox-induced cardiac toxicity in rats. Conclusion: NR can be used in combination with Dox due to its high cardioprotective effect against Dox-induced cardiomyopathy.