Oral Administration of Aluminum Chloride Inhibits Enzymes of Brush Border Membrane and Induces Metabolic Distress, Redox Imbalance, DNA Damage, and Histopathologic Alterations in Rat Intestine

Aluminum (Al) toxicity has attracted widespread attention owing to its bioavailability, environmental persistence, and detrimental impacts on human health. It is primarily absorbed into the systemic circulation via the gastrointestinal tract, which may damage the brush border membrane (BBM) and intestinal mucosal barrier, leading to numerous adverse health effects. Therefore, the present in vivo and in vitro studies were carried out to evaluate the effect of aluminum chloride (AlCl 3 ) treatment on oxidative stress parameters, cellular metabolism, membrane integrity, and DNA damage in the rat intestine. For in vivo studies, adult male Wistar rats were randomly divided into five groups, namely, the control group (C group) and AlCl 3 ‐treated groups: Al I (25 mg/kg b.wt.), Al II (35 mg/kg b.wt.), Al III (45 mg/kg b.wt.), and Al IV (55 mg/kg b.wt.). A dose‐dependent decline in the specific activities of BBM marker enzymes such as leucine aminopeptidase (LAP), alkaline phosphatase (ALP), γ‐glutamyltransferase (GGTase), and sucrase was detected, both in the mucosal homogenates and in the isolated membrane vesicles. Vmax values of the enzymes exhibited a significant decline following treatment, whereas K M values remained unaltered. Furthermore, AlCl 3 administration at all four doses altered the specific activities of energy metabolism enzymes and perturbed the cellular antioxidant status, as apparent by a significant decline in endogenous enzymatic and nonenzymatic antioxidants and enhanced lipid peroxidation (LPO). Tail migration in a single‐cell gel electrophoresis indicated extensive DNA damage in mucosal cells in all the AlCl 3 ‐treated groups; however, maximum damage was observed in rats administered AlCl 3 at a dose of 55 mg/kg b.wt. In vitro incubation of BBM vesicles with AlCl 3 (0.1–3 mM, 0–120 min) confirmed a concentration‐ and time‐dependent inhibition of BBM enzyme activities. Histological investigations revealed impaired intestinal histology concomitant with biochemical alterations. The present results indicate that aluminum‐induced oxidative stress produced substantial intestine damage, leading to altered levels of BBM, antioxidants, and carbohydrate metabolism enzymes, potentially guiding the development of protective strategies to mitigate its adverse health effects.