ABSTRACT
Cisplatin remains the standard first-line chemotherapeutic agent in the treatment of many types of cancers, but its clinical application is hindered by its severe nephrotoxicity. Previous studies reported that scutellarin enhanced the anti-cancer activity of cisplatin in lung cancer cells, with no confirmation on cisplatin-induced renal damage. Here, we investigated the nephroprotective effect of scutellarin on cisplatin-induced renal injury and its underlying mechanisms. Renal function, histological change, inflammation, apoptosis, autophagy and involved pathways were investigated. Pretreatment with scutellarin prevented cisplatin-induced decline of renal function including BUN, CRE, and histological damage. Scutellarin also reduced renal inflammation by suppressing the levels of pro-inflammatory cytokine, TNF-α and IL-6. Similarly, scutellarin administration inhibited apoptosis triggered by cisplatin through reducing the expressions of Cleaved caspase-3, Cleaved PARP, p53, and the ratio of Bax/Bcl-2. Moreover, scutellarin prevented cisplatin-induced inhibition of autophagy via enhancing LC3-II/LC3-I and Atg7, and inhibition of p62. Of note, the activations of JNK, ERK, p38 and stat3 induced by cisplatin were strikingly attenuated in scutellarin-treated mice. Thus, these results provide compelling evidence that scutellarin is a novel nephroprotectant against cisplatin-induced renal toxicity.
Subject(s)
Acute Kidney Injury/chemically induced , Acute Kidney Injury/prevention & control , Apigenin/therapeutic use , Apoptosis/drug effects , Autophagy/drug effects , Cisplatin/toxicity , Glucuronates/therapeutic use , Acute Kidney Injury/pathology , Animals , Apigenin/pharmacology , Apoptosis/physiology , Autophagy/physiology , Glucuronates/pharmacology , Inflammation/chemically induced , Inflammation/pathology , Inflammation/prevention & control , Male , Mice , Mice, Inbred C57BL , Protective Agents/pharmacology , Protective Agents/therapeutic use , Random AllocationABSTRACT
In this paper, two mathematical models, the baseline model and the intervention model, are proposed to study the transmission dynamics of echinococcus. A global forward bifurcation completely characterizes the dynamical behavior of the baseline model. That is, when the basic reproductive number is less than one, the disease-free equilibrium is asymptotically globally stable; when the number is greater than one, the endemic equilibrium is asymptotically globally stable. For the intervention model, however, the basic reproduction number alone is not enough to describe the dynamics, particularly for the case where the basic reproductive number is less then one. The emergence of a backward bifurcation enriches the dynamical behavior of the model. Applying these mathematical models to Qinghai Province, China, we found that the infection of echinococcus is in an endemic state. Furthermore, the model appears to be supportive of human interventions in order to change the landscape of echinococcus infection in this region.