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Succinate enhances hypoxia by inhibiting the prolyl hydroxylase domain proteins that are involved in the degradation of hypoxia-inducible factor (HIF)-1 alpha, leading to HIF-1 activation 70

As a result, these agents act together to cause additional oxidative damage, creating a never-ending chain reaction (also may be considered a feed-forward loop)

In the past, glucocorticoids in allergic features and ursodeoxycholic acid in cholestatic cases had been used, but there is no good evidence to support their effectiveness

Jiang Y-Z, Ma K, Cui C, Li Z-Y, Wang X-Y

Oliota AF, Penteado ST, Tonin FS, Fernandez-Llimos F, Sanches AC (2019) Nephrotoxicity prevalence in patients treated with polymyxins: a systematic review with meta-analysis of observational studies