Furthermore, by reducing bladder oxidative stress and blocking the production of nitric oxide synthase and peroxynitrite, melatonin upregulates heme oxygenase-1 (HO-1) and downregulates substance P (SP) expression, significantly improving bladder symptoms and lowering histological damage in CP-induced cystitis in rats (Table 1) [107, 108]. The gene discussed is HMOX1; the disease is chronic cystitis.