Cisplatin is a potent platinum-based anticancer drug approved by the Food Drug Administration (FDA) in 1978. Despite its advantages against solid tumors, cisplatin confers toxicity to various tissues that limit its clinical uses. In cisplatin-induced hepatotoxicity, few mechanisms have been identified, which started as excess generation of reactive oxygen species that leads to oxidative stress, inflammation, DNA damage and apoptosis in the liver. Various natural products, plant extracts and oil rich in flavonoids, terpenoids, polyphenols, and phenolic acids were able to minimize oxidative stress by restoring the level of antioxidant enzymes and acting as an anti-inflammatory agent. Likewise, treatment with honey and royal jelly was demonstrated to decrease serum transaminases and scavenge free radicals in the liver after cisplatin administration. Medicinal properties of these natural products have a promising potential as a complementary therapy to counteract cisplatin-induced hepatotoxicity. This review concentrated on the protective role of several natural products, which has been proven in the laboratory findings to combat cisplatin-induced hepatotoxicity.
Oxidative stress, inflammation and apoptosis are thought as primary mediators of cisplatin-induced hepatotoxicity. The objective of this study was to determine the protective effect of Polygonum minus essential oil in cisplatin-induced hepatotoxicity. A total of forty-two male rats were randomly divided into seven groups: control, cisplatin, β-caryophyllene 150 mg/kg (BCP), PmEO 100 mg/kg + cisplatin (PmEO100CP), PmEO 200 mg/kg + cisplatin (PmEO200CP), PmEO 400 mg/kg + cisplatin (PmEO400CP) and PmEO 400 mg/kg (PmEO400). Rats in the BCP, PmEO100CP, PmEO200CP, PmEO400CP and PmEO400 group received respective treatment orally for 14 consecutive days prior to cisplatin injection. All animals except for those in the control group and PmEO400 were administered with a single dose of cisplatin (10 mg/kg) intraperitoneally on day 15 and all animals were sacrificed on day 18. PmEO100CP pretreatment protected against cisplatin-induced hepatotoxicity by decreasing CYP2E1 and indicators of oxidative stress including malondialdehyde, 8-OHdG and protein carbonyl which was accompanied by increased antioxidant status (glutathione, glutathione peroxidase, superoxide dismutase and catalase) as compared to cisplatin group. PmEO100CP pretreatment also modulated changes in liver inflammatory markers (TNF-α, IL-1α, IL-1β, IL-6 and IL-10). PmEO100CP administration also notably reduced cisplatin-induced apoptosis significantly as compared to cisplatin group. In conclusion, our results suggested that P. minus essential oil at a dose of 100 mg/kg may protect against cisplatin-induced hepatotoxicity possibly via inhibition of oxidative stress, inflammation and apoptosis.