The Protective Effects of Daucus carota L. ssp. carota and Cannabis sativa L. Extracts against Cisplatin Induced Nephrotoxicity in Animal Models

Abstract

Cisplatin is a standard antineoplastic drug that has been incorporated in many firstline chemotherapy regimens for the treatment of solid tumors such as, advanced ovarian, lung, head and neck, testicular and bladder. However, its use is associated with dose dependent nephrotoxicity, and ongoing attempts have been made to reduce the cisplatininduced nephrotoxicity. The current study investigates the nephroprotective effects of two native Lebanese plants, Daucus carota and Cannabis sativa, in animal models. Previous studies in our laboratory showed that Daucus carota oil extract (DCOE) possesses antioxidant, anti-inflammatory, and anticancer properties. The major component of DCOE, β-2-himachalen-6-ol (HC), has been isolated and found to be a potential safe and potent chemotherapeutic agent. Additional recent studies showed that Cannabis sativa oil extract (COE) demonstrated potent anti-inflammatory effects. DCOE (100 mg/kg body weight) and HC (25 and 50 mg/kg body weight) were administered daily to rats for 10 days, and a single dose of cisplatin (7.5 mg/kg body weight) was administered on day five. In another protocol, 2.5, 5, 10, and 20 mg/kg body weight of COE were given daily to mice for three days, and cisplatin (20 mg/kg body weight) was administered on day one. Serum creatinine and urea, proteinuria, and inflammatory markers were measured. All used doses of COE showed significant decrease in serum urea; however, a significant decrease in serum creatinine was observed only at 20 mg/kg COE. On the other hand, treatment with HC (50 mg/kg) or DCOE (100mg/kg) demonstrated significant decrease in serum urea, but little or no effects was observed on serum creatinine. In addition, COE treatment caused a significant decrease in urinary albumin excretion. Furthermore, Western blot analysis with the antibodies against COX-2 was significantly lower in cisplatin-intoxicated mice with COE in comparison to mice treated with cisplatin alone. In conclusion, the current findings demonstrates that doses of HC (50 mg/kg) and DCOE (100 mg/kg), and all used doses of COE could be a promising approach to protect against cisplatin-induced nephrotoxicity, partially by ameliorating inflammatory response.