Acute and subchronic oral toxicity of fermented Crescentia cujete (L) preparation in rats

Abstract

Background: Fermented Crescentia cujete L (FC-C) has significant potential as a multimodal therapeutic agent. However, its toxicological profile remains undefined and requires comprehensive elucidation. Aim: This study assessed the acute and 90-day subchronic oral toxicity of the FC-C preparation in rat models. Methods: The Crescentia cujete fruit was fermented for 30 days before toxicity testing, and the resulting product was subsequently evaluated for acute and subchronic toxicity. A total of 100 Sprague Dawley rats were employed in this study, comprising 40 rats (20 of each sex) for the acute toxicity test and 60 rats (30 of each sex) for the subchronic evaluation. The study utilized three doses of FC-C: high (2000 mg/kg BW, equivalent to 2 mL/kg BW), medium (1000 mg/kg BW, 1 mL/kg BW), and low (500 mg/kg BW, 0.5 mL/kg BW). The control group received 2 mL of distilled water. The acute toxicity observation period lasted for 14 days, whereas the subchronic assessment spanned 90 days, followed by a 30-day recovery period to monitor reversibility. The parameters assessed included body weight, hematology, urinalysis, histopathology, malondialdehyde (MDA) levels, and antioxidant activity. All data were statistically analyzed using SPSS version 26 at a p-value of 0.05. Results: Findings from both acute and subchronic assays indicate that FC-C possesses a high safety margin, with an estimated LD50 exceeding 2000 mg/kg body weight. Long-term administration at doses up to 2000 mg/kg BW did not induce significant adverse alterations in BW, organ integrity, serum biochemistry, or tissue histopathology relative to the control group. Conversely, FC-C administration conferred beneficial effects by significantly augmenting systemic antioxidant capacity and enhancing erythrocyte stability. Conclusion: This study substantiates that the 90-day FC-C administration does not induce any adverse toxicological effects. Furthermore, the preparation positively modulates antioxidant defense mechanisms and erythrocyte quality in rat models.