Biochemical and Histopathological Evaluations of the Kidney and Liver in Ketamine-Induced Schizophrenic Model in Wistar Rats
Abstract
<h4>Background: </h4> Ketamine, a dissociative anesthetic, is widely used in experimental schizophrenia models due to its ability to mimic psychotic symptoms through N-methyl-D-aspartate (NMDA) receptor antagonism. Despite its utility, concerns remain regarding its potential systemic toxicity, particularly in the liver and kidneys. <h4>Method:</h4> This study investigated the dose- and time-dependent hepatotoxic and nephrotoxic effects of ketamine in Wistar rats using biochemical and histopathological assessments. Fifteen adult male Wistar rats were randomly assigned into three groups: control (normal saline), low-dose ketamine (50 mg/kg intraperitoneally for 14 days), and high-dose ketamine (80 mg/kg intraperitoneally for 7 days). Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), urea, and creatinine were analyzed. Liver and kidney tissues were examined using Hematoxylin and Eosin staining and graded for severity. <h4>Results:</h4> High-dose ketamine significantly increased AST (56.6%, p = 0.0007) and ALT (128.0%, p = 0.0001), indicating hepatocellular injury, while ALP remained unchanged. Mild renal impairment was observed with increased urea (6.0%, p = 0.0427), whereas creatinine levels were stable. Low-dose ketamine showed no significant biochemical alterations. Strong positive correlations were found between AST and ALT (r = 0.892, p < 0.001), and between liver enzymes and urea. Histopathological findings in the high-dose group revealed severe hepatocellular degeneration, inflammation, and vascular congestion. Renal tissues showed acute tubular necrosis, inflammation, hemorrhage, and early fibrotic changes, despite preserved glomeruli. <h4>Conclusion:</h4> In conclusion, high-dose ketamine induces significant hepatorenal toxicity, while low-dose exposure appears relatively safe. These findings highlight the importance of dose regulation and monitoring in ketamine use.
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