Insights Into Protective Mechanisms of Dandelion Leaf Extract Against Cisplatin-Induced Nephrotoxicity in Rats: Role of Inhibitory Effect on Inflammatory and Apoptotic Pathways

Abstract

Cisplatin (CP) nephrotoxicity is associated with the induction of oxidative stress, inflammation, and apoptosis. Several studies demonstrated the antioxidant, anti-inflammatory, and antiapoptotic effects of dandelion leaf extract (DLE); therefore, this research aimed to investigate the protective effects of DLE against CP-induced nephrotoxicity. Thirty-two male Wistar rats were divided into 4 groups: normal control, DLE control received 500 mg/kg daily for 11 days, intoxicated group received vehicle daily for 11 days and a single dose of CP (7 mg/kg, intraperitonealp) on day 5, and DLE þ CP group received DLE (500 mg/kg) daily for 11 days plus a single dose of CP (7 mg/kg) on day 5. The dose of DLE is selected based on a dose-effect study using different doses. Dandelion leaf extract pretreatment ameliorated CP-induced nephrotoxicity as evident by histopathological examination, alleviating CP-induced elevation in serum creatinine, blood urea nitrogen, oxidative stress marker (thiobarbituric acid reactive substances), tumor necrosis factor-a (as inflammatory cytokine), and caspase-9 and caspase-3 (as apoptotic markers). In addition, DLE reduced nuclear factor-kB and cytochrome c expression, and DNA fragmentation. It also maintained levels of reduced glutathione, superoxide dismutase, and serum albumin. Thus, the present study shows that DLE is a promising nephroprotective agent for CP-induced nephrotoxicity through antioxidant, anti-inflammatory, and antiapoptotic activities.

TLR4/Inflammasomes Cross-Talk and Pyroptosis Contribute to N-Acetyl Cysteine and Chlorogenic Acid Protection against Cisplatin-Induced Nephrotoxicity

“…This is mostly associated with the production of ROS, which damages mitochondrial membrane lipids and culminates in increased caspase-3 activity. Additionally, nephroprotection mediated by various pharmacological modalities is associated with a reduction in caspase-3 activity [ 26 , 27 , 28 , 29 , 30 ], further confirming the role of caspase-3 in Cp-induced nephrotoxicity [ 26 , 28 , 29 , 30 ].…”

Protective role of the dandelion extract against the blood–liver axis, cell membranes, and anemia disorder in sodium benzoate‐exposed rats

“…Dandelion leaf extract treatment improved cisplatin‐induced nephrotoxicity and increased cisplatin‐induced elevations in serum creatinine, blood urea nitrogen, and oxidative stress markers. Dandelion extract has a promising nephroprotective effect through antioxidant, anti‐inflammatory, and antiapoptotic effects 63 . Dandelion has been used extensively as a diuretic in phytotherapy without a prior clinical trial.…”

“…Dandelion extract has a promising nephroprotective effect through antioxidant, anti-inflammatory, and antiapoptotic effects. 63 Dandelion has been used extensively as a diuretic in phytotherapy without a prior clinical trial. Clare et al 64 investigated the effect of dandelion extract intake on increased frequency and volume of urination.…”

Effect of Taraxacum officinale L. ethanol extract against kidney injuries induced by paracetamol in rats

“…In a study where different dandelion leaf methanol extracts (250, 500 and 750 mg/kg) were examined for cisplatin nephrotoxicity, it was stated that all doses reduced serum creatinine and urea levels (the most effective dose; 500 mg/kg) and the extract did not have any side effects [47]. Dandelion extracts applied in different doses against nephrotoxicities caused by various chemicals (CCl4, cisplatin, etc.)…”

“…Dandelion, which is widely found in the world, has a diuretic effect, and this is attributed to the richness of sesquiterpene lactone content [60]. In a rat study where dandelion leaves methanol extract (500 mg/kg) was applied against cisplatin nephrotoxicity; it was reported that the extract increased SOD activity and GSH level and further decreased LPO level [47]. In an experiment given dandelion extract (100 mg/kg) against kidney damage caused by carbon tetrachloride in rats; it lowered the level of MDA, but there was no statistical difference in GSH and GPx level/activity [49].…”