Possible Ameliorative Potentials of Pentoxifylline Against Alzheimer's Disease Induced in a Rat Model

Background. Alzheimer’s disease is the most common cause of dementia, and no current therapy reverses the underlying neurodegeneration. In rats, chronic aluminium chloride (AlCl3) reproduces the core lesions of the disease: amyloid-β deposition, tau hyperphosphorylation, reactive astrogliosis, and hippocampal neuronal loss. Pentoxifylline (PTX) is an oral phosphodiesterase inhibitor with anti-inflammatory, antioxidant, and haemorheological actions, making it a plausible candidate for repurposing. Material and Method. Forty male Wistar rats were divided into four equal groups (n = 10): vehicle, PTX, AlCl3, and AlCl3 + PTX. AlCl3 (100 mg/kg/day, i.p.) and PTX (10 mg/kg/day, i.p.) were given for 60 days. We assessed histology and immunohistochemistry (Aβ42, AT8, GFAP), hippocampal ELISA panels, and qRT-PCR for BAX and Bcl-2, and compared groups by one-way ANOVA with Tukey’s HSD. Results. AlCl3 produced severe hippocampal pathology. Neuronal density fell by 64 %, the pyknotic index reached 72 %, Congo red revealed about 11 birefringent amyloid plaques per field, and the GFAP area fraction rose almost fourfold; TNF-α, IL-6, and ICAM-1 rose 1.9- to 4.1-fold. Tissue Aβ42 climbed 4.6-fold, acetylcholine fell to 23 % of control, and the BAX/Bcl-2 ratio more than doubled. PTX shifted every parameter back toward normal (p < 0.001): amyloid burden dropped 58–68 %, phospho-tau 57–59 %, astrogliosis 40–43 %, and the cognitive deficits 46–48 %. TNF-α and MDA returned to control values. Conclusion. PTX produced substantial, though partial, neuroprotection. The pattern fits the drug’s known pharmacology, but the study is hypothesis-generating rather than confirmatory: it used male rats only, a concurrent rather than delayed treatment schedule, and a single dose. Delayed-treatment, both-sex, and dose–response studies are needed before any clinical step. KEY WORDS: Alzheimer disease; Amyloid beta-peptides; tau Proteins; Gliosis; Oxidative stress; Pentoxifylline.