Sub-acute toxicity study of methanol extract of Tetrorchidium didymostemon leaves using biochemical analyses and gene expression in Wistar rats

Tetrorchidium didymostemon is widely used by traditional medicine practitioners to manage and treat several diseases. Despite its known ethnomedicinal uses, there are no scientific studies on the toxic effects of this plant. This study was performed to evaluate the potential toxicity of methanol extracts Tetrorchidium didymostemon leaves through sub-acute oral administration in rats. Twenty four (24) male albino rats (Wistar strain) of average weight 150 ± 20 g were randomly divided into 4 groups of 6 rats each. Group 1 was the control while groups 2, 3 and 4 were administered 100, 300 and 600 mg/kg body weight of the plant extracts respectively for 14 consecutively days. The extract did not induce any treatment related changes in body weight, organ/body weight ratio, biochemical parameters (aspartate transaminase, alanine transaminase, total protein, albumin, creatinine and urea), oxidative stress indices (malondialdehyde, superoxide dismutase and reduced glutathione) and histopathology (liver and kidney) of the treated groups when compared to the control. However, at 600 mg/kg body weight dose, the extract caused a significant (p < 0.05) decrease in hemoglobin level, packed cell volume and the expression of albumin gene of rats. Similarly, at 300 and 600 mg/kg body weight, the extract also caused a non-significant (p > 0.05) decrease in red blood cell count. Furthermore, the extract at 100 and 300 mg/kg body weight induced a significant (p < 0.05) increase in the expression of tumor necrosis factor - alpha and kidney injury molecule - 1 (KIM-1) genes. Catalase gene expression especially in the kidney was up-regulated in the groups administered the extract. Our study suggests that oral administration of T. didymostemon leaves extract is relatively safe. However, there is need for caution due to the observed changes in hematological profile, up-regulation of KIM-1 genes as well as down regulation of albumin gene.