Neuroprotective effect of nebivolol against cisplatin‐associated depressive‐like behavior in rats

Abstract

One-third of cancer patients undergoing chemotherapy treatment often display symptoms of depression leading to poor adherence and decreased quality of life. Thus, this study aimed to investigate the possible protective effect of nebivolol against cisplatin-associated depressive symptoms in adult male rats. Nebivolol is a highly cardioselective β-adrenergic receptor blocker that possesses endothelium-dependent vasodilator properties and antioxidant capacities. Animals were allocated into four groups. Group one was given aqueous solution of carboxymethyl cellulose and served as control, group two was given nebivolol (10 mg/kg p.o., daily), group three was given cisplatin (2 mg/kg i.p. once per week) for 10 consecutive weeks and group four was treated with cisplatin concomitantly with nebivolol as per above schedule. Cisplatin-treated rats showed an increase in both depressive-like behaviors in open-field and forced swimming tests. In addition, histopathological examination revealed cortical encephalomalacia along with hippocampal neuronal degeneration and kidney dysfunction. In parallel, cisplatin administration prominently reduced GABA and elevated glutamate levels in the cortical and hippocampal tissues. Furthermore, it resulted in a significant decline in cortical and hippocampal brain-derived neurotrophic factor and nitric oxide contents concomitantly with a marked decrease in endothelial- and an increase in inducible-nitric oxide synthase genes expression. On the other hand, treatment with nebivolol effectively mitigated the aforementioned cisplatin-associated behavioral, biochemical, and histopathological alterations without changing its antitumor activity as evidenced by sulforhodamine B cell survival assay. Taken together, our results suggest that nebivolol may offer a promising approach for alleviating depressive symptoms associated with the use of cisplatin.

Empagliflozin attenuates transient cerebral ischemia/reperfusion injury in hyperglycemic rats via repressing oxidative–inflammatory–apoptotic pathway

“…Behavioral and neurological functions were assessed for all animal groups via performing open field and Garcia neurobehavioral tests, respectively. Open field test measures the locomotor activity of the rats by measuring their ambulation frequency in a given field for 3 min [22,23]. Additionally, Garcia neurobehavioral test measures neurological defect by scoring six individual tests evaluating spontaneous activity, symmetry in the movement of the four limbs, forepaw outstretching, climbing, body proprioception, and response to vibrissae touch [24].…”

The Effects of Satureja hortensis L. Extract on Cisplatin-Induced Behavioral Alterations in the Tail Suspension Test

“…One of the most recently reported manifestations of adverse effect of cisplatin on CNS has clinical form with characteristics of increased depressive state level (30). The prodepressant action of cisplatin, by means of behavioral tests results, in that study (performed on rats) was accompanied with prooxidant alterations in both cortex and hippocampus.…”

“…The prodepressant action of cisplatin, by means of behavioral tests results, in that study (performed on rats) was accompanied with prooxidant alterations in both cortex and hippocampus. Also, neuronal degeneration in hippocampus paralleled the decline in BDNF and GABA content, as well as the increase in hippocampal glutamate (30).…”

“…The offered explanation is that increased motor activity observed in the tests for depressive level estimation (such as TST) may rather be considered as the behavioral outcome of anxiety-induced overreacting than antidepressant action. When comparing the results for prodepressant action of cisplatin (30) and increased locomotor response in TST observed in this study, we must take into consideration two important information. Firstly, those two studies were performed with the significantly different protocols: the prodepressant effect was reported in the study with the chronic exposure to cisplatin (10 weeks), while the opposite effect on depressive level was obtained in the study with a single dose of cisplatin.…”

The Evaluation of the Effects of N-Acetylcysteine on Cisplatin-Induced Alterations in Exploratory Activity in Elevated Plus Maze Test in Rats

“…In humans, neurotoxicity is usually manifested by peripheral nerves dysfunction and sensory disorders, seizures, reduced cognitive abilities and various mood disorders (8,9). Studies performed on animal experimental models confirmed cisplatin-induced neurotoxicity by means of motor impairment (10), decline of cognitive functions (11), mood disorders (12) and alterations in nociception (13).…”