Bulletin of Pharmaceutical Sciences. Assiut · Published 2026-07-30 · DOI 10.21608/bfsa.2026.504905.3191
Nadheerah Falih Neamah, Hussein Mohammed Abbood, ALI BASIM MATROOD
Abstract Background: While pregabalin treats neuropathy and epilepsy, high-dose abuse raises severe safety concerns. Its subacute high-dose on electrolyte balance, hepatic, and renal functions remain poorly understood. Objectives: This study evaluated the subacute pregabalin administration in the liver and kidneys of adult albino rats using a multiparametric assay. Methods: Twenty-four male albino rats were divided into four groups (n=6) and orally administered pregabalin (50, 150, or 300 mg/kg) for eight days. Assessed parameters included renal function (BUN, creatinine), liver enzymes (ALT, AST, ALP, GGT), protein synthesis, electrolytes, pancreatic enzymes, oxidative stress, and cardiac biomarkers. Hepato-renal tissues underwent histopathological examination. Results : Pregabalin dramatically a decrease of total protein, albumin, and magnesium (p<0.05) while enhancing BUN, BUN/creatinine ratio, phosphorus, and Ca×P product (all p<0.05). Although AST enhanced at 50 and 300 mg/kg (p=0.0066), ALT exhibited a U-shaped signal with a major increase only at 50 mg/kg (p=0.0001). TBA (oxidative stress) enhanced in a dose-dependent pattern (p=0.0099). The hepatorenal histopathological results revealed dose-dependent congestion, inflammation, and structural injury. The values of creatinine, ALP, GGT, lipase, amylase, CK, LDH, and electrolytes failed to change. In conclusion: subacute pregabalin at elevated therapeutic concentrations leads to oxidative stress, diminished protein synthesis, prerenal azotemia, hepatocellular dysfunction (with a U-shaped ALT response), and mineral imbalances. Dose-dependent organ injury is proven by histological evidence. Such results indicate concerns regarding the safety of pregabalin abuse, especially in hepato-renal impaired patients.
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Neamah, N., Abbood, H., MATROOD, A. (2026). Subacute Pregabalin Administration Induces Dose-Dependent Hepatorenal Toxicity and Mineral Imbalance in Rats: A Multiparametric Assessment. Bulletin of Pharmaceutical Sciences. Assiut. https://doi.org/10.21608/bfsa.2026.504905.3191