Effect of Freeze-dried Extracts of Tetradenia Riparia (Hochst.) Codd Leaves and Stem in 5-fluorouracil Induced Acute Hepatotoxicity on Sprague Dawley Rats

Abstract

5-Fluorouracil (5FU) is the first line antineoplastic drug for managing advanced gastrointestinal cancers e.g., colon cancer as FOLFIRI or FOLFOX based regimens. Despite its effectiveness and affordability in cancer treatment, severe toxicities e.g., nephrotoxicity, cardiotoxicity, and hepatotoxicity, remain major concerns in clinical use often causing its withdrawal from treatment. The current study investigated the effects of aerial extracts of Tetradenia riparia on acute hepatotoxicity in 5 FU treated Sprague Dawley rats . Oral toxicity of Tetradenia riparia was evaluated using the Up-and-Down Procedure(UDP) as per the OECD number 425. Fifteen (15) Sprague Dawley rats 8-12 weeks old were assigned into negative and experimental (Tetradenia riparia treated) groups and treated as per the protocol and monitored for 14 days for signs of toxicity. Twenty-five (25) mixed Sprague Dawley rats 8-12 weeks old were randomized into negative control (20 mg/kg 5-FU), positive control (20mg/kg 5-FU +250 mg/kg Silymarin), low dose test (20 mg/kg 5-FU +50 mg/kg T.r), medium dose test (20 mg/kg 5-FU +100 mg/kg T.r ) and high dose test (20 mg/kg 5-FU +200 mg/kg T.r) and treated for 5 days for determination of anti-hepatotoxic effects. Biochemical assays and Raman studies of antioxidant defense and mitochondrial functions were analyzed and liver histology performed. Statistically significant values were obtained in liver function profile, antioxidant, cytochrome c and Coenzyme Q levels. The extracts of Tetradenia riparia leaves and stem possessed significant antioxidant, antidyslipidemic, anti-inflammatory, antihyperglycemic, and antihepatotoxic activities in a rodent model of 5-FU induced hepatotoxicity. This study unraveled unknown antidyslipidemic and antihyperglycemic activities of this plant species as well as the relatively underreported metabolic effects of 5-fluorouracil. The extract of Tetradenia riparia has a potential role in neoadjuvant and adjuvant chemotherapies to combat 5 FU associated hepatotoxicity.