Antioxidant Effects ofSatureja hortensisL. Attenuate the Anxiogenic Effect of Cisplatin in Rats

Abstract

Numerous adverse effects of cisplatin-based therapy are usually accompanied by enhanced oxidative damage and cell apoptosis in various tissues. Even neurotoxic manifestations of cisplatin administration, such as the anxiogenic effect, appear along with the increased oxidative stress and apoptotic indicators in certain brain regions. Thirty-five Wistar albino male rats were divided into seven groups: control, cisplatin (received a single dose of cisplatin: 7.5 mg/kg), three groups with oral administration ofSatureja hortensisL. methanolic extract (SH) (low: 50 mg/kg, middle: 100 mg/kg, and high dose: 200 mg/kg) along with cisplatin application, a group with the extract in high dose alone, and a silymarin group (cisplatin and silymarin: 100 mg/kg), in order to evaluate the antioxidant effects of SH on cisplatin-induced increase in the anxiety level. After completing 10-day pretreatments, behavioral testing was performed in the open field and the elevated plus maze, followed by an investigation of oxidative stress and apoptosis parameters in hippocampal tissue samples. Cisplatin administration resulted in anxiogenic-like behavior, increased lipid peroxidation, and proapoptotic markers accompanied by the decline in antioxidant and antiapoptotic defense. The administration of extract alone did not significantly alter any of the estimated parameters. When applied along with cisplatin, SH in a dose of 100 mg/kg induced the significant anxiolytic effect with concomitant recovery of antioxidant and antiapoptotic activity indicators, while both lower and higher doses of the extract failed to improve the adverse effects of cisplatin administration. The beneficial effects of the middle dose of SH were equivalent to the same dose of silymarin, as a “golden standard.” Our results indicate that the antioxidant supplementation with SH in an optimal dose significantly improved the oxidative status and it had antiapoptotic effect in the rat hippocampus disturbed by cisplatin administration, which was accompanied with attenuation of cisplatin-induced anxiogenic effect.

N-Acetylcysteine Protects against the Anxiogenic Response to Cisplatin in Rats

“…In addition, the anxiogenic response to cisplatin was also represented by means of decreased locomotor activity in both applied behavioral tests ( Figure 1D,E and Figure 2C,D). The anxiety-like outcome of cisplatin administration observed in this study is in line with the results of our recent investigation [22], but the anxiogenic feature of cisplatin was also reported for single administration of cisplatin in a two-fold higher dose [21]. As expected, the cisplatin-induced anxiogenic effect was also described in a study with prolonged cisplatin administration (5 weeks) with a lower dose (5 mg/kg) compared to the dose applied in this study [23].…”

The Beneficial Role of Filipendula ulmaria Extract in Prevention of Prodepressant Effect and Cognitive Impairment Induced by Nanoparticles of Calcium Phosphates in Rats

“…Prefrontal cortex (PFC) homogenates were prepared according to the standard procedure previously established in our lab, as reported by Kumburovic and coworkers [ 32 ] and Vukovic and colleagues [ 33 ], with the chemicals listed in Supplementary file 2 . Principally, phosphate-buffered saline (PBS, pH 7.4) was used for PFC tissue homogenization, and after centrifugation at 4000 rpm for 15 min at 4°C, the supernatant was separated and used for further analyses.…”

Antioxidant Supplementation in the Treatment of Neurotoxicity Induced by Platinum-Based Chemotherapeutics—A Review

“…Silibinin is one of the components in silymarin complex mixture which also contains three more flavonolignans (silychristin, silydianin, and taxifolin) and its use is mainly focused on liver disorders treatment [ 149 ]. Silymarin in rats, at a concentration of 100 mg/kg, decreased the anxiogenic effect of cisplatin treatment and exhibited significant antioxidant activity in brain tissues by lowering lipid peroxidation and elevating GSH levels and CAT and SOD activities [ 127 ].…”

“…Its extract showed significant protective activity against oxaliplatin-induced neurotoxicity in vitro and reduced caspase-3 activity in rat astrocytes without the reduction of oxaliplatin cytotoxicity on HT-29 cells [ 135 ]. Satureja hortensis aerial part extract, applied in rats at three different concentrations (50, 100 and 200 mg/kg) along with cisplatin injection, exhibited strong anxiolytic activity and lowered apoptotic parameters in rat hippocampal tissues [ 127 ]. Moreover, it was able to significantly reduce the oxidative stress in brain tissues by alleviating CAT and SOD activities and GSH levels and decreasing the levels of lipid peroxidation indicators.…”

“…Sci. 2020, 21, x FOR PEER REVIEW 18 of 28brain tissues by lowering lipid peroxidation and elevating GSH levels and CAT and SOD activities[127].…”