Behavioral and genotoxic evaluation of rosmarinic and caffeic acid in acute seizure models induced by pentylenetetrazole and pilocarpine in mice

Abstract

The goal of this study was to investigate the effects of rosmarinic acid (RA) and caffeic acid (CA) in the acute pentylenetetrazole (PTZ) and pilocarpine (PIL) seizure models. We also evaluated the effect of RA and CA on the diazepam (DZP)-induced sleeping time test and its possible neuroprotective effect against the genotoxic damage induced by PTZ and PIL. Mice were treated intraperitoneally (i.p.) with saline, RA (2 or 4 mg/kg), or CA (4 or 8 mg/kg) alone or associated to low-dose DZP. After, mice received a single dose of PTZ (88 mg/kg) or PIL (250 mg/kg) and were monitored for the percentage of seizures and the latency to first seizure (LFS) >3 s. Vigabatrin and DZP were used as positive controls. In the DZP-induced sleeping time test, mice were treated with RA and CA and 30 min after receiving DZP (25 mg/kg, i.p.). The alkaline comet assay was performed after acute seizure tests to evaluate the antigenotoxic profiles of RA and CA. The doses of RA and CA tested alone did not reduce the occurrence of seizures induced by PTZ or PIL. The association of 4 mg/kg RA + low-dose DZP was shown to increase LFS in the PTZ model, compared to the group that received only the DZP. In the DZP-induced sleeping time test, the latency to sleep was reduced by 4 mg/kg RA and 8 mg/kg CA. The PTZ-induced genotoxic damage was not prevented by RA or CA, but the PIL-induced genotoxic damage was decreased by pretreatment with 4 mg/kg RA (in cortex) and 4 mg/kg CA (in hippocampus). In conclusion, RA and CA presented neuroprotective effect against PIL-induced genotoxic damage and reduced the latency to DZP-induced sleep. Of the rosmarinic acid, 4 mg/kg enhanced the DZP effect in the increase of latency to clonic PTZ-induced seizures.

Efficiency of the interfacial charge transfer complex between TiO2 nanoparticles and caffeic acid against DNA damage in vitro: A combinatorial analysis

“…To put it simply, the ICT complex and its components are not genotoxic under the stated experimental conditions. CA is a well-known antioxidant with a strong reducing ability, 43 and, in addition, it did not exhibit genotoxicity in the comet assay experiments using concentrations that exceed the highest concentration in this study. However, the genotoxicity of TiO 2 NPs is still a matter of debate in the literature.…”

“…These results are in agreement with published data concerning the antigenotoxic effect of unmodified TiO 2 NPs, 22 and antigenotoxic effect of CA. 43 Post-treatment with the ICT complex formed between TiO 2 and CA displayed antigenotoxic effect at lower concentrations (0.5-1.6 mg mL -1 ICT; mole ratio c(TiO 2 )/c(CA) = 8). However, at higher concentrations (>5 mg mL -1 ICT; mole ratio c(TiO 2 )/c(CA) = 8), the ICT complex showed no beneficial effect on H 2 O 2 damaged cells.…”

Phytochemical and Network Pharmacology Based Evaluation of Antiepileptic Potential of Identified Metabolites in Argimone mexicana

“…In a study cited by revealed that polyphenols such as ferulic acid possess neuroprotective effects against oxidative and inflammatory stress. [35][36][37][38] Besides, in the study conducted by Li et al, revealed that berberine strongly attenuates the toxic effects of oxidative and inflammatory stress by amelioration of SOD and reduction of NOS oxidative enzyme, MAPKs and interleukins. [39]…”

Lacosamide improves biochemical, genotoxic, and mitochondrial parameters after PTZ‐kindling model in mice

“…All drugs were dissolved in saline (NaCl 0.9%) solution. The doses of LCM and DZP were chosen based on previous studies [14–17]. The PTZ dose used was 50 mg/kg s.c., obtained through a pilot test.…”

“…The study design is summarized in Figure . Animals were given intraperitoneal injections of saline and DZP (2 mg/kg), 30 min before the subconvulsive stimuli (PTZ 50 mg/kg, s.c.) according to Coelho et al [17,19]. LCM (20, 30, and 40 mg/kg) was administered by gavage one hour before subconvulsive stimuli so that the plasmatic concentration of drug was adequate [13].…”