Protective Effects of Pelargonium graveolens Essential Oil on Methomyl-Induced Oxidative Stress and Spatial Working Memory Impairment in Association with Histopathological Changes in the Hippocampus of Male Wistar Rats

Abstract

Introduction: Methomyl (MET) is a carbamate insecticide, used in agriculture and public health to eliminate harmful insects. Besides its advantages in agriculture, it causes neurotoxic effects. The aim of this study was to evaluate the effect of MET on Spatial Working Memory (SWM), oxidative stress parameters, and histopathological changes in the hippocampus, as well as the possible protective role of Pelargonium graveolens Essential Oil (EO).

Methods: Male Wistar rats were randomized into four groups of six animals: group I as the control that received the vehicle; group II received EO (75 mg/kg b.w), group III received MET (2 mg/kg b.w); and group IV received both MET and EO. The rats were administered the respective doses orally by gavage for 28 days. SWM was assessed using Y-maze on the day before the first treatment and day 28 after the last dose. They were sacrificed by decapitation and their brains were taken for assessing oxidative stress parameters and histopathological analysis.

Results: MET treatment caused SWM deficits. Furthermore, drastic changes were observed in aspartate transaminase, alanine aminotransferase, and alkaline phosphatase activities. The level of malondialdehyde significantly increased, whereas antioxidant (glutathioneS-transferase and catalase) enzyme activities significantly decreased. The CA1 region of the hippocampus of rats exposed to MET revealed severe histological alterations. However, supplementation with EO improved SWM and partially restored the activities of antioxidant systems and prevented neuronal cell damage.

Conclusion: P. graveolens EO has the potential in mitigating most of the adverse effects in the hippocampus and prevents SWM impairment induced by MET toxicity.

Keywords: Hippocampus; Methomyl; Oxidative stress; Pelargonium graveolens; Spatial working memory.

Figure 1.

Effects of MET and MET+Pelargonium graveolens EO on SWM 28 days after treatment A: Spontaneous alternation; B: The number of total arm entries; Values are given as Mean±SEM for a group of six animals each; ** P<0.01 for all groups in comparison with the control group; ^# P<0.05 in terms of in comparison with the MET+EO MET group; ^*,^**,^***, ^#,^##: Lack of the statistical significance

Figure 2.

Effects of MET and MET+Pelargonium graveolens EO administration on reduced glutathione (nmol/mg of protein) and TBARS (nmol of MDA/mg of protein) levels in the hippocampus 28 days after treatment. The values are expressed as mean±SEM in each group. P<0.05, **P<0.01, ***P<0.001 for all groups in comparison with the control group and # P<0.05 and ## P<0.01 in terms of MET+EO in comparison with the MET group. ^*,^**, ^***, ^#,^##: Lack of the statistical significance

Figure 3.

Effects of MET and MET+Pelargonium graveolens EO treatment on CAT, GST, and GPx activities in the hippocampus tissue after 28 days Values are given as Mean±SEM for each group of six animals; ^**P<0.01; ^***P<0.001 for all groups in comparison with the control group; ^#P<0.05; ^##P<0.01 in terms of MET+EO in comparison with the MET group; *,**,***, ^#,^##: Lack of the statistical significance

Figure 4.

Photomicrograph showing the CA1 hippocampal area in the control rats. Normal cells: N. (Nissl staining ×400).

Figure 5.

Photomicrograph illustrating the CA1 hippocampal area in the group treated with essential oil of Pelargonium graveolens. Normal cells: N. (Nissl staining ×400).

Figure 6.

Photomicrograph illustrating the CA1 hippocampal area in the MET-treated group. Affected cells: A. (Nissl staining ×400).

Figure 7.

Photomicrograph showing the CA1 hippocampal area in the groups treated with MET and co-treated with essential oil of Pelargonium graveolens. Normal cells: N, affected cells: A. (Nissl staining ×400).