Oral administration of Nigella sativa oil ameliorates the effect of cisplatin on membrane enzymes, carbohydrate metabolism and oxidative damage in rat liver

Toxicol Rep. 2016 Feb 13;3:328-335. doi: 10.1016/j.toxrep.2016.02.004. eCollection 2016.


Cisplatin (CP) is a potent anti-cancer drug widely used against solid tumors. However, it exhibits pronounced adverse effects including hepatotoxicity. Several strategies were attempted to prevent CP hepatotoxicity but were not found suitable for therapeutic application. Nigella sativa has been shown to prevent/reduce the progression of certain type of cardiovascular, kidney and liver diseases. Present study investigates whether N. sativa oil (NSO) can prevent CP induced hepatotoxic effects. Rats were divided into four groups viz. control, CP, NSO and CPNSO. Animals in CPNSO and NSO group were administered NSO (2 ml/kg bwt, orally) with or without single hepatotoxic dose of CP (6 mg/kg bwt, i.p.) respectively. CP hepatotoxicity was recorded by increased serum ALT and AST activities. CP treatment caused oxidant/antioxidant imbalances as reflected by increased lipid peroxidation and decreased enzymatic and non-enzymatic antioxidants. Furthermore, the activities of various carbohydrate metabolism and membrane enzymes were altered by CP treatment. In contrast, NSO administration to CP treated rats, markedly ameliorated the CP elicited deleterious alterations in liver. Histopathological observations showed extensive liver damage in CP treated animals while greatly reduced tissue injury in CPNSO group. In conclusion, NSO appears to protect CP induced hepatotoxicity by improving energy metabolism and strengthening antioxidant defense mechanism.

Keywords: ACPase, acid phosphatase; ALP, alkaline phosphatise; ALT, alanine aminotransferase; AST, aspartate aminotransferases; Antioxidant; BBM, brush border membrane; BBMV, BBM vesicles; BUN, blood urea nitrogen; CAT, catalase; CP, cisplatin; Carbohydrate metabolism; Chl, cholesterol; Cisplatin; FBPase, fructose 1,6; G6PDH, glucose 6-phosphate dehydrogenase; G6Pase, glucose 6-phosphatase; GGTase, γ-glutamyl transferase; GR, glutathione reductase; GSH, glutathione; GSHPx, glutathione peroxidise; GST, glutathione S-transferase; Glc, glucose; H2O2, hydrogen peroxide; HK, hexokinase; LAP, leucine aminopeptidase; LDH, lactate dehydrogenase; LPO, lipid peroxidation; MDA, malondialdehyde; MDH, malate dehydrogenase; ME, malic enzyme; NADP, nicotinamide adenine dinucleotide phosphate; NADPH, nicotinamide adenine dinucleotide phosphate reduced; NSO, Nigella sativa oil; Nigella sativa oil; PLs, phospholipids; PUFA, polyunsaturated fatty acids; Pi, inorganic phosphate; ROS, reactive oxygen species; SH, sulfhydryl; SOD, superoxide dismutase; Scr, serum creatinine; TCA, tricarboxylic acid; TR, thioredoxin reductase; μm, micrometer.