Figure 5

The two therapeutic mechanisms of MnDPDP and Ca₄Mn(DPDP)₅, i.e., MnSOD mimetic activity and metal chelation activity of DPDP/CaDPDP, and the meaning of them during acute increase in oxidative/nitrosative stress and that caused by a prolonged increase in oxidative/nitrosative stress, such as from retention of Pt²⁺ in the body. During the acute increase in the cellular stress, MnSOD mimetic activity is the most important mechanism to balance the cellular stress burden, although metal chelation also plays an important role. Pharmacokinetic behavior of MnDPDP in healthy volunteers suggests that the MnSOD mimetic activity of MnDPDP last no longer than 2 hours post-injection, whereas the chelation activity lasts about 12 hours¹⁵. During prolonged increase in cellular stress, causing irreversible inactivation of endogenous mitochondrial MnSOD (the most important endogenous cellular defensive against increased oxidative/nitrosative stress²), metal chelation is probably the main mechanism to balance the burden, such as that caused by retention of the transitional metal Pt²⁺, where chelation of Pt²⁺ may be of a particularly importance.