The subacute toxicity effects of aged Tualang (Koompassia excelsa) honey with high 5-hydroxymethylfurfural content in rats

Abstract

Tualang honey (TH) stored for more than 12 months is characterised as aged TH (ATH). Surprisingly, majority of the general public is unaware of the recommended consumption period for honey, since most honeys marketed locally have no determined expiry dates. The present work determined 5-hydroxymethylfurfural (HMF) content in four-year stored ATH, and evaluated the effects of ATH upon repeated dose during 28-day oral toxicity study. The HMF concentration in ATH was determined using HPLC. Animal toxicity study was conducted by treating Sprague Dawley rats with distilled water (control), 200, 1,000, 2,000 mg/kg/day ATH, or 2,000 mg/kg/day fresh TH for 28 days. The HMF concentrations were significantly high, exceeding the international maximum limit set for tropical honey (> 80 mg/kg). ATH did not affect the general conditions and behaviour of the rats. Nevertheless, female rats exhibited significant increase in creatinine and oestradiol levels when treated with 1,000 mg/kg/day ATH. The left kidney’s weight of those treated with 200 mg/kg/day ATH also significantly decreased. Further, histological findings revealed that there were reductions in the Bowman’s space and poorly defined glomerular boundary in female rats treated with 1,000 mg/kg ATH. In contrast, all parameters in male rats were statistically unaffected by ATH. The present work suggested that ATH with remarkably higher HMF concentrations modified the kidneys of female rats but not those of the male rats, which indicated sex-based variation. The no-observed-adverse-effect level was 2,000 mg/kg/day for male rats, and less than 200 mg/kg/day for female rats.