Biochemical and Histopathological Evaluations of the Kidney and Liver in Ketamine-Induced Schizophrenic Model in Wistar Rats
Okwuchukwu Adachukwu Heavenah, Ugochukwu Samuel Aguwa, Ukoha Ukoha
Preprints.org July 3, 2026 preprint DOI: 10.20944/preprints202607.0226.v1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial |
|---|---|
| Sample size | 15 |
| Population | Adult male Wistar rats |
| Intervention | Ketamine |
| Dose | 50 mg/kg intraperitoneally for 14 days (low dose); 80 mg/kg intraperitoneally for 7 days (high dose) |
| Duration | 14 days (low-dose group) and 7 days (high-dose group) |
| Measures | Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), urea, creatinine, Hematoxylin and Eosin staining |
| Topics | Esketamine Ketamine |
| Key findings | High-dose ketamine (80 mg/kg intraperitoneally for 7 days) increased AST by 56.6% and ALT by 128.0% and raised urea by 6.0%, with histopathological liver and kidney injury; low-dose ketamine (50 mg/kg for 14 days) produced no significant biochemical changes. The authors conclude that high-dose ketamine induces hepatorenal toxicity while low-dose exposure appears relatively safe. |
Abstract
Background: 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.
Method: 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.
Results: 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.
Conclusion: 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.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |