Carvacrol inhibits cadmium toxicity through combating against caspase dependent/independent apoptosis in PC12 cells. (December 2019) - Banik, Subrata
Abstract: Carvacrol is a monoterpenic phenol found in essential oils, is considered a safe food additive, and possesses various therapeutic properties. Numerous studies have also deciphered the protective role of carvacrol on various cytotoxicities. We clarify the effects of carvacrol on cadmium-induced apoptosis in PC12 cells. Carvacrol while co-exposed with cadmium for 48 h raised PC12 cell viability in comparison to only cadmium exposed group. The co-exposure increased the cellular glutathione levels and promoted the expression of glutathione reductase. The magnitude of DNA fragmentation caused by cadmium was also ameliorated by carvacrol. Flow cytometry exhibited the apoptosis rate augmented by cadmium was reduced by carvacrol. Western blotting revealed that cadmium and carvacrol co-exposure alleviated the cadmium-induced down-regulations of mammalian target of rapamycin (mTOR), protein kinase B (Akt), nuclear factor kappa-light-chain-enhancer of activated B cells (NFКB), extracellular signal-regulated kinase-1 (ERK-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) expressions. The co-exposure also reversed action of cadmium by suppressing the cleavage of caspase 3 and reducing the cytosolic levels of cytochrome c and apoptosis inducing factor (AIF). Moreover, carvacrol upon co-exposure significantly increased the intracellular metallothionein content. In conclusion, carvacrol strongly reduced cadmium-triggered oxidative stress and caspase-dependent and caspase-independent apoptosis in PC12 cells. Highlights: Cd 2+ induced oxidative stress and apoptotic death in PC12 cells. Carvacrol promoted survival of PC12 cells by reducing apoptosis rate. Carvacrol reversed the Cd 2+ -triggered downregulation of mTOR, Akt, NFК B, ERK-1 and Nrf2. Upon co-exposure with Cd 2+, carvacrol reduced cleaved caspase 3, cytosolic cytochrome c and AIF. The co-exposure of Cd 2+ and carvacrol induced metallothionein expression in the cells.