Epilepsy in association with other dementias e.g., multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD) and migraine, cerebrovascular disease, tetanus, meningitis, poliomyelitis, and Japanese encephalitis are only a few examples of neurological disorders (WHO, 2006). These disorders are frequently stigmatized because they are socially incapacitating and cause behavioral disorders, cognitive impairment, depression, and suicide (De Boer et al., 2008).

Epilepsy is a neurological status with common symptoms of seizure. The status epilepticus (SE) refers to protracted or continuous epileptic episodes andis linked to a high death rate (Giovannini et al., 2017). Multiple biological alterations may occur in epileptic discharges, including altered neurogenesis, redox imbalance, upregulation of inflammatory cytokines, activation of cell death pathways, and changed in expression of receptor of aminobutyric acid (GABA) (Lin et al., 2020).

Epileptic population have changes in their cognition and behavior (Devinsky et al., 2018). SE has been linked to significant cerebral damage in several animal and human studies. This increases the chance of subsequent epileptic episodes and hippocampal neuronal loss (Riban et al., 2002). Furthermore, neuronal loss and significant gliosis are major features in case of medial temporal lobe epilepsy (MTLE), along with hippocampal sclerosis.

The hippocampus as a part of the limbic system, is important for learning and memory. Cognitive impairment in epileptic patients may resulted from alterations in the hippocampus (Rodriguez-Alvarez et al., 2015). Although the consequences of epileptogenesis is not understood, many experimental models indicated the importance of antioxidants, histology, on learning and memory disturbances, and other factors (El-Hameed et al., 2021; Mátyás et al., 2021).

Epileptogenesis is promoted by different inflammatory responses, which increases neuronal excitability and the permeability of the blood–brain barrier(De Simoni et al., 2000). Electrolyte imbalances, particularly those affecting sodium, calcium, and magnesium, is the initial step in seizure diagnosis (Oguni, 2004). Excessive reactive oxygen species can result in enzyme inhibition, lipid peroxidation and DNA damage, all of which can lead to neuron death (Shekh-Ahmad et al., 2019). As a result, reducing inflammatory cascades and oxidative stress, particularly in the hippocampus, could be a useful method for treating and/or preventing epilepsy. Pilocarpine hydrochloride (PILO) induced higher malondialdehyde (MDA) levels and lower superoxide dismutase (SOD); catalase, (CAT); glutathione peroxidase (GPX) levels, indicating oxidative stress in the hippocampus. These features are linked to hippocampi's neuronal death (Santos et al., 2009). Many natural substances have been attempted as antioxidants to combat the potentially damaging effects of free radicals and to lessen the damage caused by oxidants.

The anti-epileptic valproic acid (VPA) has been linked to male infertility (Iamsaard et al., 2017). In both epileptic males and experimental animals, VPA reduces viable reproductive indices and hormones (Bialer and Yagen, 2007). VPA administration has been linked to atrophy of the testis, epididymis, seminal vesicles and prostate gland (Krogenaes et al., 2008). It's been proven that testicular atrophy is linked to poor reproductive outcomes and low sex hormone levels (Iamsaard et al., 2015).

Neurotoxins found in arthropod venoms have a strong affinity for different receptors, transporters, and ion channels in both neuronal and glial membranes in brain tissue (Soares-Silva et al., 2022).Some active neurotoxins like melittin, the mast-cell-degranulating (MCD) peptide, adolapin, apamin, many enzymes e.g. phospholipase [PL] A2); physiologically active amines (such as histamine and adrenaline), and other non-peptide constituents with many pharmacological qualities, are all known to be present in bee venom (BV) (Son et al., 2007). Furthermore, studies on the biological activities of BV revealed that it has anti-inflammatory and anticancer properties (Wehbe et al., 2019) and anti-neuroinflammatory activity (Silva et al., 2015). These toxins can alter synapses because they act specifically on various ion channels and receptors; as well as generate and propagate action potentials, are major targets for the nervous system (Escoubas et al., 2008).

BV which is also known as apitoxin is a complex mixture of substances. It is used to defend the bee colony. It contains several biologically active peptides, including melittin apamin, adolapin, mast cell degranulating peptide and many enzymes. Plus, also non-peptide components, such as a variety of bioamines like apamin, histamine, procamine, serotonin, and nor-epinephrine, which facilitate nerve transmission and healing in a variety of nerve disorders. This gives bee venom the ability to travel along the neural pathways from the spine to various trigger points and injured areas to help repair nerve damage and restore mobility. BV has traditionally been used as a non-steroidal anti-inflammatory drug for the relief of pain and the treatment of different diseases, such as rheumatoid arthritis and multiple sclerosis as well as in the treatment of tumors (El-Bassiony et al., 2016). Although such pharmacological properties, the significant effect of BV on rats suffering from epilepsy is still unknown. Based on the previous review, the current research was aimed to assess the modulatory effect of BV on hippocampal neurons, oxidative stress, alternations on behavior and histological alternations in liver and testis tissues. As a result, the key findings regarding the use of wasp and BV in the treatment of the most common neurodegenerative illnesses.