The Role of Alpha Lipoic Acid and Tempol Against Liver Injury after Acetaminophen Subacute Exposure in Mice

Abstract

| Acetaminophen (APAP) is a widely used analgesic and antipyretic drug, but it can cause liver damage when taken in high doses or for prolonged periods. Alpha Lipoic Acid (ALA) and Tempol are two antioxidants that have been shown to protect against various forms of oxidative stress and inflammation. This study explored the hepatoprotective effects of Alpha Lipoic Acid (ALA) and Tempol against subacutely repeated acetaminophen (APAP) exposure in a murine model. Fifty male Balb-c mice were divided into five groups. Groups received 700 mg/ kg.BW of APAP and oral treatments: G1 (distilled water, negative control), G2 (no treatment, positive control), G3 (Par+Tempol, 20 mg/kg.BW), G4 (Par+ALA, 20 mg/kg.BW), G5 (Par+Tempol+ALA, 10 mg/kg.BW each). Half animals were sacrificed after 30 days, the rest after one week of treatment withdrawal. Investigation included body weight, biochemical markers (ALT, GGT, PT, INR), and liver histopathology. After 30 days, G5 showed a significant (P ≤ 0.05) increase in body weight (29.2±1.32) compared to the positive control (20.8±1.2). After withdrawal, G5 displayed a significant (P ≤ 0.05) increase in body weight(31.4±1.17) compared to all other experimental groups G1(29.2±0.37),G2(25.8±2.4), G3(25.0±1.38) and G4(27.2±1.02). Positive control (117 ± 42.9) had significantly (P ≤ 0.05) increased ALT after 30 days, but all experimental groups G1(6.10 ± 1.81), G3(6.96 ± 3.33), G4(10.4 ± 5.56) and G5(7.62 ± 2.34) showed decreased ALT after withdrawal in comparison with positive control(16.1 ± 6.8). GGT levels were significantly increased in G4(2.05 ± 1.14) after 30 days, while G5(1.92 ± 0.97) showed a significant (P ≤ 0.05) decrease after withdrawal. PT increased significantly (P ≤ 0.05) in G4(2.05 ± 1.14) after 30 days but decreased in G3(5.01 ± 1.02), G4(3.85 ± 1.46), and G5(3.85 ± 1.46) after withdrawal. INR significantly increased in G4(16.6 ± 0.39) after 30 days but decreased in G3(13.1 ± 0.72), G4(3.96 ± 0.04), and G5(14.6 ± 0.66) after withdrawal. Liver sections displayed necrotic hepatocytes in G3 after 30 days, and G4 showed normal features. G5 exhibited normal hepatocytes after 30 days, with mild cellular swelling after withdrawal. These findings suggest the potential of ALA and Tempol in mitigating APAP-induced subacute toxicity, indicating a promising therapeutic avenue. However, further research is essential to elucidate the precise mechanisms, and caution is warranted in interpreting these preliminary results. The clinical implications could revolutionize APAP-induced toxicity management, emphasizing the need for continued research in this area.