Redox Rep. 2013;18(2):56-62.
Erythrocyte caspase-3 and antioxidant defence is activated in red blood cells and plasma of type 2 diabetes patients at first clinical onset.
Savu O, Bradescu OM, Serafinceanu C, Iosif L, Tirgoviste CI, Stoian I.
National Institute for Diabetes N.C. Paulescu, Bucharest, Romania.
OBJECTIVES: We studied erythrocyte (RBC) caspase-3 activity and oxidative status in plasma and RBCs of 33 patients with type 2 diabetes at first clinical onset and 23 age-matched non-diabetes control subjects.
METHODS: Caspase-3 activity was assayed during the life span of RBCs; lipid peroxides and total antioxidant capacity (TEAC) were assessed in plasma and RBCs as indicators of oxidative stress and non-enzymatic antioxidant defence; and superoxide dismutase, catalase, and glutathione peroxidase activity were measured in RBCs as enzymatic antioxidants.
RESULTS: We found that, compared to controls, RBCs caspase-3 is activated early in type 2 diabetes (P < 0.05); TEAC and malondialdehyde increased in plasma of patients with early diabetes, even when hypertension and macroangiopathy were present (P < 0.01); and RBCs TEAC, malondialdehyde (P < 0.01), superoxide dismutase, and glutathione peroxidase (P < 0.05) exhibited similar behaviour in patients with diabetes and hypertensive patients with diabetes.
DISCUSSION: Increased antioxidant defence in plasma and RBCs of early type 2 diabetes patients is a potential mechanism that can overcome oxidative damage induced by reactive oxygen species overproduction, and occurs even in RBCs with a decreased life span. This observation could provide a possible explanation for the controversial effects of antioxidant supplementation in diabetes patients.
Oxidative damages result in specific cellular and tisular lesions due to either excess of oxygen reactive species (i.e. oxygen free radicals) and/or defective antioxidant production. Redox systems consist of various enzymatic and non-enzymatic components which can be found in either blood or other tissues aimed to limit oxidative damage. The blood is considered a tissue with high energetic demands, where antioxidant defence and oxidative damage is amplified. Diabetes, and type 2 diabetes mellitus (T2DM) especially, is a worldwide health problem where redox imbalance is involved in disease progression and occurrence of its specific chronic complications. Erythrocytes (or red blood cells, RBCs) are mainly targeted by oxidative damage. Though, there is a lack of data on non-enzymatic antioxidant capacity while specific redox enzymatic activities (i.e. superoxide-dismutase – SOD, catalase – CAT, and glutathione peroxidase – GPX, which are essential against oxygen free radicals defence) are controversial in RBCs of patients with T2DM. Moreover, it has been recently shown that oxidative damage decreases life span of RBCs in diabetes.
We therefore aim to study oxidative status in the plasma and RBCs from patients with T2DM at first clinical onset, with no previous medical history of diabetes.
We found that oxidative stress and total antioxidant status increases in the plasma while free radical production and both non-enzymatic and enzymatic antioxidant activity are early activated in RBCs of patients with T2DM.
Our findings show that antioxidant defence is upregulated while oxidative aggression increases in blood stream of patients with T2DM from first clinical onset. Though, the compensatory efficiency of the response remains to be elucidated, especially when the oxidative stress mediated shortened life span of RBCs in diabetes is taken into account. We therefore measured caspase-3 activity as a well-accepted marker of RBCs life span. We found that RBCs caspase-3 activity is increased in patients with not previously known medical history of T2DM.
We concluded that the pattern of defence against free radical aggression is activated early in the blood stream of patients with T2DM, and occurs even in RBCs with a shortened life span.
Our result could represent a possible explanation for the controversial effects of antioxidants supplementation in diabetes.