Propylene Glycol induces Excessive Neurodegeneration in Combination with Amyloid Beta1-40 Toxin in Male Rat Hippocampus

Introduction: Propylene glycol (PG) is frequently used as a solvent for various medications. However, there is substantial evidence of Propylene glycol toxicity, such as depression, agitation, and seizures, particularly when used in combination with other drugs. Here, we aimed to study the effect of Propylene glycol administration in combination with amyloid β₁₋₄₀ injection on hippocampal neurons. Material & Methods: Thirty-six male Wistar rats were randomly divided into four groups: sham, amyloid β₁₋₄₀ injection group, Propylene glycol group, and amyloid β₁₋₄₀ + Propylene glycol group. Alternation behavior, number of neurons in the hippocampus, lipid peroxidation markers, and superoxide dismutase levels were analyzed in all rats. Results: When Propylene glycol was co-administered with amyloid β₁₋₄₀, a notable reduction in the mean neuronal count was observed in the CA1, CA3, and DG regions compared with the amyloid β₁₋₄₀ only injected animals (P < 0.05). Furthermore, Propylene glycol induced an increase in lipid peroxidation markers (10.78 ± 0.4) and a decrease in antioxidant content (2.8 ± 0.17) when administered with amyloid β₁₋₄₀, compared to the animals that received only amyloid β₁₋₄₀ (P < 0.05). A similar pattern was found in alternation behavior compared with the group with amyloid β₁₋₄₀ injection (P < 0.001). Conclusion: Propylene glycol could produce excessive neurotoxicity in regions of the hippocampus when co-administered with amyloid β₁₋₄₀. It likely increases lipid peroxidation and reduces superoxide dismutase in the rat brain. The use of different agents as a vehicle should be considered, especially in the elderly.