Abstract

Cadmium (Cd) and lead (Pb) are persistent environmental pollutants capable of inducing oxidative stress, inflammation, mitochondrial dysfunction, and damage to vital organs. This study evaluated the protective effects of the methanolic seed extract of Dennettia tripetala against cadmium- and lead-induced toxicity in Wistar rats. Forty-eight adult male Wistar rats (150–200 g) were randomly assigned into six groups: normal control, toxic control, low-dose extract, high-dose extract, standard drug, and extract-only groups. Toxicity was induced by oral administration of cadmium chloride and lead acetate for 28 days, while treatment groups received graded doses of the extract. Biochemical, oxidative stress, inflammatory, mitochondrial, histopathological, and tissue metal accumulation parameters were assessed using standard procedures. Exposure to cadmium and lead significantly (p < 0.05) increased serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, urea, creatinine, malondialdehyde, tumor necrosis factor-alpha, and interleukin-6 levels compared with the control group. In contrast, antioxidant markers including superoxide dismutase, catalase, glutathione peroxidase, and reduced glutathione were significantly reduced. Histopathological examination revealed marked hepatic and renal lesions, accompanied by mitochondrial impairment and elevated tissue concentrations of cadmium and lead. Treatment with the methanolic seed extract of Dennettia tripetala, particularly at 400 mg/kg body weight, significantly restored antioxidant status, improved mitochondrial function, reduced inflammatory responses, ameliorated tissue damage, and decreased heavy metal accumulation in vital organs. The findings demonstrated that Dennettia tripetala seed extract possesses potent antioxidant, anti-inflammatory, and metal-chelating properties that mitigate cadmium- and lead-induced toxicity in Wistar rats.