Toxicological profile of antimicrobial metabolites of endophytic fungal isolates of <i>Synclisia scabrida</i> Miers

Abstract

Purpose: To evaluate the acute and subacute toxicity of antimicrobial secondary metabolites of endophytic fungi of Synclisia scabrida Miers using rat model. Methods: Acute oral toxicity was determined following Lork’s method. Sub-acute toxicity study was evaluated by administering 200 and 400 mg/kg body weight of the fungal metabolites to rats orally as a single dose for three days, while the control group received normal saline (0.5 mL). The effects of the metabolites on haematological and biochemical parameters were determined using standard methods. The histopathology of the kidney, liver and heart was observed. Results: The acute oral toxicity studies showed that S1, S2, and R1 metabolites were safe above 5000 mg/kg bodyweight within 24 h. The LD50 of L1 metabolite was below 1000 mg/kg bodyweight. Above 1000 mg/kg bodyweight, the rats given L1 metabolite showed major physical changes, which included initial sluggishness and hyperactivity, resulting in the death of the rats within 20 min of administration. The metabolites showed significant differences (p = 0.0001) in means of the baselines and after-treatment haematological parameters at the administered doses. There were no significant changes (p = 0.05) in serum ALT, AST, ALP, and creatinine levels of rats. The urea and total protein increased considerably (p = 0.002 and 0.000, respectively) on administration of the metabolites to the rats at the dose levels. The histopathological examination showed varying degrees of degeneration and necrosis of renal tubular epithelial cells and hepatocytes with normal myocardial histo-architecture. Conclusion: Majority of secondary metabolites of endophytic fungi of Synclisia scabrida Miers (S1, S2 and R1 metabolites) caused no death of the rats, even at the highest doses tested, indicating the safety of the metabolites. However, these metabolites should be used at moderate doses as high doses may cause mild organ toxicity.