Effect of Time-dependent Administration of Activated Charcoal on Some Biochemical Parameters of Albino Rats Exposed to Paracetamol Toxicity
Adeshina, Covenant Oluwadamilola *
Department of Clinical Chemistry, Faculty of Medical Laboratory Science, Rivers State University, Nkpolu-Oroworukwo, Port Harcourt, Nigeria.
Uchechukwu Achor Obisike
Department of Clinical Chemistry, Faculty of Medical Laboratory Science, Rivers State University, Nkpolu-Oroworukwo, Port Harcourt, Nigeria.
Waribo, Helen Anthony
Department of Clinical Chemistry, Faculty of Medical Laboratory Science, Rivers State University, Nkpolu-Oroworukwo, Port Harcourt, Nigeria.
*Author to whom correspondence should be addressed.
Abstract
Aim: To investigate the time-dependent effects of activated charcoal on cytochrome P450 (CYP2E1) activity, oxidative stress (SOD), liver injury enzymes (AST, ALT, ALP, and GGT), and hepatic function parameters (total protein, albumin, and total bilirubin) in albino rats exposed to paracetamol toxicity.
Study Design: A controlled experimental toxicological animal study was undertaken.
Place and Duration of Study: The study was conducted in the Department of Clinical Chemistry, Faculty of Medical Laboratory Science, Rivers State University, Port Harcourt, Nigeria, for 21 days following 14 days of animal acclimatisation.
Methodology: Forty-five albino rats (150-180 grams) were randomly divided into nine groups (n = 5). Median lethal dose (LD50) values were predetermined using the arithmetic method of Karber. Group 1 served as the negative control. Group 2 received paracetamol only (325 mg/kg), whereas Group 3 received activated charcoal only (540 mg/kg). Groups 4-9 received paracetamol (325 mg/kg), followed by activated charcoal (540 mg/kg) administered by gavage at specified intervals (immediately and after 10, 20, 30, 40, or 50 minutes) once daily for 21 days. Serum levels of CYP2E1, SOD, liver enzymes (AST, ALT, ALP, and GGT), and liver function parameters (total protein, albumin, and total bilirubin) were quantified using sandwich ELISA and spectrophotometric techniques. Statistical analyses were performed using GraphPad Prism 10.0 for Windows. Differences in mean values among the groups were evaluated using one-way ANOVA followed by Tukey's multiple-comparisons test. P < .001 was considered statistically significant at a 95% confidence level.
Results: Paracetamol exposure (Group 2) caused hepatotoxicity, significantly increasing CYP2E1 (264.0±14.68), ALT (119.9±9.770), AST (147.9±14.92), ALP (212.8±12.26), GGT (44.40±5.329), and total bilirubin (3.44±0.377), while significantly reducing SOD (21.20±1.721), total protein (4.516±0.30), and albumin (2.134±0.260) compared with the negative control (P < .001). Immediate administration of activated charcoal (Group 4) significantly reversed these changes. However, delayed administration progressively reduced the therapeutic efficacy of activated charcoal across Groups 5-9 (P < .001). The R ratio indicated a hepatocellular injury pattern that became more pronounced with delayed intervention (P < 0.0001).
Conclusion: Activated charcoal demonstrated hepatoprotective and antioxidant effects against paracetamol toxicity. Its efficacy was time-dependent, with the greatest benefit observed when it was administered immediately after exposure, whereas delayed administration resulted in a progressive reduction in protection.
Keywords: Activated charcoal, paracetamol toxicity, CYP2E1, superoxide dismutase, hepatotoxicity, time-dependent rescue, Karber's method