Isoniazid (Isonicotinic hydrazide) is an antibacterial agent used primarily as a tuberculostatic.

Isoniazid is a prodrug that requires activation by the mycobacterial catalase-peroxidase enzyme (KatG) to an active form that then exerts a lethal effect on an intracellular target or targets. [1] Isoniazid upregulates the expression of an operon containing five FAS II components, including kasA and acpM. Isoniazid results in the accumulation of ACP-bound lipid precursors to mycolic acids that are 26 carbons long and fully saturated. [2] Isoniazid enters the mycobacterial cell by passive diffusion. Isoniazid itself is not toxic to the bacterial cell, but acts as a prodrug and is activated by the mycobacterial enzyme KatG, a multifunctional catalase-peroxidase that has other activities, including peroxynitritase and NADH oxidase. Isoniazid inhibits cell wall lipid synthesis, coupled with the findings that inhibitory INH adducts of NAD+/NADP+ are formed from the isonicotinoyl radical, leading the field away from this area. [3] Isoniazid induces a concentration-dependent (0-40 mM) cytotoxic effect in day-1 treated HepG2 cells and not significantly affected by decreases in intracellular GSH concentrations. [4]

Isoniazid increases CYP2E1 protein, and the 6-hydroxychlorzoxazone formation rate is increased by 2.7 and 2.2-fold in liver and kidney, respectively. Isoniazid decreases liver and kidney 20-HETE content to 34% and 15.6% of control, respectively, without significantly altering tissue 19-HETE concentration. [5]