Ameliorative effects of hexane extract of Garcinia kola seeds Heckel ( Clusiaceae) in cisplatin-induced hepatorenal toxicity in mice

Garcinia kola seed is used to manage liver diseases in ethnomedicine. However, there is limited information on its role in Cisplatin (CIS)-induced toxicity. Here, we investigated the potential of hexane extract of Garcinia kola (HEGK) in lessening CIS-induced hepatorenal- and gene- toxicity. Male mice (22 ± 3 g) randomly assigned into groups (n = 5) were treated for five days: Corn oil only, HEGK (200 mg/kg), CIS (20 mg/kg; i.p; 48-hours), CIS + HEGK (100 mg/kg), CIS + HEGK (200 mg/kg), CIS + Quercetin (25 mg/kg), and Quercetin(25 mg/kg). Corn oil, HEGK, and Quercetin were administered daily by gavage. GC-MS revealed the presence of 9,19-Cyclolanost-24-en-3-ol as the most abundant component in HEGK, with an LC₅₀ of 1023 µg/mL. HEGK significantly (p < 0.05) scavenged DPPH, inhibited lipid peroxidation and exhibited reducing activity dose-dependently. CIS treatment increased (p < 0.05) urinary albumin and creatinine by 18 and 56%, respectively, serum levels of total bilirubin, creatinine, and hepatic transaminases, while albumin decreased (p < 0.05) by 57%. CIS treatment increased renal and hepatic malondialdehyde (MDA) levels by 67 and 70% individually, while the activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) levels were decreased (p < 0.05). Furthermore CIS-induced the formation of mononucleated polychromatic erythrocytes (mnPCEs) 150% in the bone marrow of mice. Histology revealed necrosis of hepatocytes, congestion of renal interstitial vessel, and hyperplasia of the Kupffer cells. Pretreatment with HEGK reduced the levels of MDA, mnPCEs, and increased the activities of antioxidant enzymes and restored GSH to levels comparable in control mice. Taken together, HEGK ameliorated CIS-toxicity via the activation of the antioxidative pathways and mitigated genotoxicity by mitigating mnPCEs formation in mice.

Keywords: Cisplatin; Garcinia kola; antioxidant enzymes; genotoxicity; hepatorenal toxicity; oxidative stress.