Some human activities, such as the constant use of fossil fuels, have led to the appearance of acid rain, which in turn may dissolve aluminum from the Earth's solid surface. Dissolved due to lower pH, aluminum can easily pollute surface water that humans use or accumulate in plants[1] part from the mentioned natural source of aluminum, almost every individual comes into contact with aluminum via the skin due to the use of antiperspirants[2]. The gastrointestinal tract is probably the main route of aluminum body entrance, although uptake from polluted food is limited Nowadays, aluminum salts are an integral part of some vaccines, and even though the dose of aluminum per vaccine is low, after application, 100% of aluminum reaches circulation [3]. Its widespread use in households, such as utensils and cookware, also contributes to human exposure[4]. The respiratory tract may also serve as an entrance way for aluminum, as individuals who smoke cigarettes are exposed to aluminum to a greater extent On the other side, some chemical features, such as its amphoteric properties, are used in wastewater quality improvement, acting as a microorganism and phosphate absorber, as well as alumina (Al2O3) catalyst precursors Aluminum exposure via ingested water and foods [5] begins from the earliest infant days, as there are large levels of aluminum in infant milk formulas[6].

The hazardous effects of aluminum on humans are indisputable; prolonged exposure to aluminum can lead to the appearance of anemia[7] and cause deterioration of bone microarchitecture [8], [9]. Additionally, the majority of other organ systems are affected by aluminum, such as the respiratory [10], immunological, and nervous systems[11]. Aluminum is neurotoxic and has been implicated in neurodegenerative diseases, especially Alzheimer's disease (AD) [11], [12], [13]. Possible molecular mechanisms involved in aluminum-induced toxicity include oxidative stress, cytotoxicity, genotoxicity, pro-inflammatory effects, enzyme dysfunctions, metabolic disturbances, membrane disruption, microtubule disruption, necrosis, and apoptosis [14]. Additionally, aluminum can disrupt the homeostasis of some metals[15] such as iron, and lead to cell death known as ferroptosis [3] and interfere with cellular and metabolic processes, including neurotransmission [16]. Experimental studies in rats have also shown that aluminum disrupts the cholinergic system, leading to neurobehavioral disturbances [17].

Nickel (Ni) is a common environmental contaminant that is mostly introduced into the environment through industrial activities, such as mining, extraction, refining, alloying, stainless steel production, electroplating, and welding. This is due to its unique chemical and physical properties, including its exceptional resistance to corrosion. [18]. The reported increase in the use of Ni has raised serious public health concerns [19]. Thus, the increase in its industrial application has sparked considerable worries about its effects on human health.

The oxidative paradox is essential for fulfilling critical cellular functions and is also necessary for proper immune system functioning. However, excessive release of oxygen radicals may cause cell injury and eventually some form of cell death either apoptosis or necrosis. Various chemicals can trigger the generation of reactive oxygen species (ROS), which can be harmful to genetic information and cause mutations in cells. ROS modulates expression of several pro- and anti-apoptotic proteins [20], amplify the oxidation of membrane fatty acids, and impair cell permeability, protein oxidation, and DNA degradation. Evolution took care of that all living organisms, including most primitive once, have developed defensive systems to protect themselves against oxygen radicals detrimental effects. The body's antioxidant systems, including superoxide dismutase (SOD), catalase (CAT), and glutathione enzymes (glutathione peroxidase (GPX) and glutathione reductase (GR)), participate in neutralizing oxidative radicals. Although inflammation is critical for host defence, excessive inflammation can be harmful or even fatal [21]. Cyclooxygenase-2 (COX-2) mediates the conversion of free arachidonic acid to prostaglandins, whereas cyclooxygenase-1 (COX-1) drives the initial phase of acute inflammation. COX-2 upregulation occurs within several hours [22]and activates signalling pathways that control cell proliferation [23] and inhibit apoptosis [24]. Proinflammatory cytokines such as interleukin (IL) 1β, IL-6, and tumor necrosis factor (TNF)-α are attractive multi-biomarkers in determining immune system dysfunction (Feng et al., 2021), and metals are known to induce oxidative damage and inflammatory responses in experimental animal models [25], [26].

Acetylcholinesterase (AChE) plays a crucial role in the rapid hydrolysis of the neurotransmitter acetylcholine in the central and peripheral nervous system, and it may also participate in non-cholinergic mechanisms related to neurodegenerative diseases. In addition to the basal ganglia, the role of the cerebellum in the pathophysiology of dystonia has been reported [27]. There is bidirectional communication between the basal ganglia and cerebellum [28], [29], with a short-latency cerebellar modulation of the basal ganglia [30] that passes through the cerebellar vermis. Hence, the disruption of acetylcholine activity in the cerebellar vermis could play a part in the pathophysiology of dystonia[31]. Brain-derived neurotrophic factor (BDNF) supports the survival and maintenance of many neurons, including certain cholinergic neurons [32]. BDNF overexpression increased lifespan and rescued locomotor activity [32], [33].

In addition to having a detailed understanding of the toxicity of individual toxicants, there is a quest to understand the toxic effects of exposure to mixtures of toxicants (Olmstead et al., 2005). Previous studies have reported the toxicity and tissue bioaccumulation profiles of single heavy metals [34], [35], but usually, human exposure to multiple heavy metals occurs concurrently, especially in the coastal regions of Niger Delta Nigeria, where we have reported a cocktail of these metals in vegetables, meat, fish, etc. [36], [37]. The exposure combinations of Al and Ni can lead to a 'cocktail' effect. In cocktail poisoning, exposure to several chemicals from different sources in doses near or well below regulatory-permitted levels may engender additive, synergistic, antagonistic, or potentiate effects determined by toxicodynamic or toxicokinetic interactions [38]. Information is sparse on the interactions among different chemical mixtures, whereas literature is inundated with single chemical exposure, which are poor simulations of real-life exposure scenarios.

The objective of the present study was to evaluate the impact of Ni and Al mixtures on the motor activity of male albino rats by evaluating the oxido-inflammatory responses, AChE activity, and BDNF/NGF levels in the cerebellum of male albino rats exposed to low doses of Ni, Al, and Ni and Al mixture over a 90-day period.