CORRESPONDENCE
ELEVATED
LIPID PEROXIDATION
LEVELS IN RED BLOOD CELLS OF STREPTOZOTOCIN-TREATED
To the Editor:
The elegant study by Jain et al’ shows elevated lipid peroxidation levels in red blood cells (RBC) of diabetic (DM) rats. This increase was evident 2 and 4 months after inducing DM with streptozotocin. Furthermore, this change was almost completely reversed by treatment with insulin. We have shown that prostacyclin (PGI,) synthesis by aortic rings is reduced in the DM rat 2 months after injecting streptozotocin.2.3 This change was also almost completely reversed by treatment with insulin. The same pattern was observed in rat penile vascular tissue.3 These findings are of interest because free radicals are thought to damage the vascular endothelium (a major site of PGI, synthesis) and alter the composition of membrane phospholipids (the storage site of prostaglandin precursors), possibly resulting in reduced PGI, synthesis.4 The associations outlined here suggest that the RBC changes
DIABETIC
RATS
reported by Jain et al’ may reflect lipid peroxidation in other tissues. Thus, the measurement of RBC lipid peroxidation levels could be used as an index of peripheral tissue free radical load. There may be an additional association between RBC peroxidation and PGI, release. We have not been able to show any inhibition of aortic PGI, in DM rats 1 week after streptozotocin administration.2,3 Did Jain et al observe a similar time-dependent situation with RBC lipid peroxidation in their DM model? J. Y. Jeremy L. H. Breimer C.S. Thompson D.P. Mikhailidis
Department of Chemical Pathology and Human Metabolism Royal Free Hospital and School of Medicine (University of London) London, England
REFERENCES 1. Jain SK, Levine SN, Duett J, et al: Elevated lipid peroxidation
levels in red blood cells of streptozotocin-treated diabetic rats. Metabolism 39:971-9751990 2. Jeremy JY, Thompson CS, Mikhailidis DP, et al: Fasting and diabetes mellitus elicit opposite effects on agonist-stimulated prostacyclin synthesis by the rat aorta. Metabolism 36:616-620, 1987
3. Jeremy JY, Thompson CS, Mikhailidis DP, et al: Experimental diabetes mellitus inhibits prostacyclin synthesis by the rat penis: Pathological implications. Diabetologia 28:365-368, 1985 4. Stam H. Hulsmann WC, Jongkind JF, et al: Endothelial lesions, dietary composition and lipid peroxidation. Eicosanoids 2:1-14,1989
REPLY To the Editor:
The letter of Drs Jeremy and his colleagues in response to our report on red blood cells (RBC) lipid peroxidation in streptozotocintreated diabetic rats’ is very thoughtful and we very much appreciate it. We agree with Jeremy et al that oxygen radicals appear to be an important factor in the cellular damage of diabetes mellitus (DM). Previous studies2 have also shown that even in an in vitro system, exposure of RBC to elevated glucose levels caused peroxidation of membrane lipids and generation of oxygen radicals. The oxidative damage to lipids was blocked when inhibitors of oxygen radicals or cytochrome P-450 were used. Studies’ on diabetic patients found a significant correlation between the level of membrane lipid peroxidation with the glycosylated hemoglobin (GHb), an index of mean blood glucose levels in the preceding 2 to 3 months. It seems that cellular damage due to hyperglycemia involves a glucose metabolite such as NADPH, which can stimulate cytochrome P-450 activity and thereby oxygen radicals generation. Hunt et al’ also have shown that glucose can generate oxygen radicals in a cell-free system. Gillery et al’ suggest that oxygen free radicals are formed in
442
increasing amounts in DM by an electron exchange occurring between the sugar moiety of glycated proteins and molecular oxygen. Recently, Yaguchi et al’ have reported the presence of malonyldialdehyde in renal tissues of non-obese diabetic mice, and Schwartz et al’ have shown increased oxidation of some amino acids in the RBC membranes of diabetics with elevated GHb values. This suggests that hyperglycemia can cause cellular damage directly by generating oxygen radicals or indirectly by inhibiting prostacyclin (PGI,) synthesis.8a9 Since it is easier to obtain samples of RBC than of other tissues, it is a reasonable suggestion of Jeremy and his colleagues that measurement of lipid peroxidation in RBC may reflect changes in other tissues as well, and could be used as an index of peripheral tissue free radical load. However, more studies are needed to assess time course over which these changes occur, as well as the simultaneous measurement of lipid peroxidation in RBC compared with other tissues in an animal model. For example, membrane damage in one tissue may start at an earlier stage of diabetes than another tissue, depending on the htioxidants level or activities of antioxidative enzymes. There are more and more studies in support of hyperglycemiainduced oxygen radical generations and its role in the cellular
Metabolism, Vol40, No 4 (April), 1991: pp 442443
ELEVATED
LIPID PEROXIDATION
LEVELS IN RED BLOOD CELLS OF STREPTOZOTOCIN-TREATED
To the Editor:
The elegant study by Jain et al’ shows elevated lipid peroxidation levels in red blood cells (RBC) of diabetic (DM) rats. This increase was evident 2 and 4 months after inducing DM with streptozotocin. Furthermore, this change was almost completely reversed by treatment with insulin. We have shown that prostacyclin (PGI,) synthesis by aortic rings is reduced in the DM rat 2 months after injecting streptozotocin.2.3 This change was also almost completely reversed by treatment with insulin. The same pattern was observed in rat penile vascular tissue.3 These findings are of interest because free radicals are thought to damage the vascular endothelium (a major site of PGI, synthesis) and alter the composition of membrane phospholipids (the storage site of prostaglandin precursors), possibly resulting in reduced PGI, synthesis.4 The associations outlined here suggest that the RBC changes
DIABETIC
RATS
reported by Jain et al’ may reflect lipid peroxidation in other tissues. Thus, the measurement of RBC lipid peroxidation levels could be used as an index of peripheral tissue free radical load. There may be an additional association between RBC peroxidation and PGI, release. We have not been able to show any inhibition of aortic PGI, in DM rats 1 week after streptozotocin administration.2,3 Did Jain et al observe a similar time-dependent situation with RBC lipid peroxidation in their DM model? J. Y. Jeremy L. H. Breimer C.S. Thompson D.P. Mikhailidis
Department of Chemical Pathology and Human Metabolism Royal Free Hospital and School of Medicine (University of London) London, England
REFERENCES 1. Jain SK, Levine SN, Duett J, et al: Elevated lipid peroxidation
levels in red blood cells of streptozotocin-treated diabetic rats. Metabolism 39:971-9751990 2. Jeremy JY, Thompson CS, Mikhailidis DP, et al: Fasting and diabetes mellitus elicit opposite effects on agonist-stimulated prostacyclin synthesis by the rat aorta. Metabolism 36:616-620, 1987
3. Jeremy JY, Thompson CS, Mikhailidis DP, et al: Experimental diabetes mellitus inhibits prostacyclin synthesis by the rat penis: Pathological implications. Diabetologia 28:365-368, 1985 4. Stam H. Hulsmann WC, Jongkind JF, et al: Endothelial lesions, dietary composition and lipid peroxidation. Eicosanoids 2:1-14,1989
REPLY To the Editor:
The letter of Drs Jeremy and his colleagues in response to our report on red blood cells (RBC) lipid peroxidation in streptozotocintreated diabetic rats’ is very thoughtful and we very much appreciate it. We agree with Jeremy et al that oxygen radicals appear to be an important factor in the cellular damage of diabetes mellitus (DM). Previous studies2 have also shown that even in an in vitro system, exposure of RBC to elevated glucose levels caused peroxidation of membrane lipids and generation of oxygen radicals. The oxidative damage to lipids was blocked when inhibitors of oxygen radicals or cytochrome P-450 were used. Studies’ on diabetic patients found a significant correlation between the level of membrane lipid peroxidation with the glycosylated hemoglobin (GHb), an index of mean blood glucose levels in the preceding 2 to 3 months. It seems that cellular damage due to hyperglycemia involves a glucose metabolite such as NADPH, which can stimulate cytochrome P-450 activity and thereby oxygen radicals generation. Hunt et al’ also have shown that glucose can generate oxygen radicals in a cell-free system. Gillery et al’ suggest that oxygen free radicals are formed in
442
increasing amounts in DM by an electron exchange occurring between the sugar moiety of glycated proteins and molecular oxygen. Recently, Yaguchi et al’ have reported the presence of malonyldialdehyde in renal tissues of non-obese diabetic mice, and Schwartz et al’ have shown increased oxidation of some amino acids in the RBC membranes of diabetics with elevated GHb values. This suggests that hyperglycemia can cause cellular damage directly by generating oxygen radicals or indirectly by inhibiting prostacyclin (PGI,) synthesis.8a9 Since it is easier to obtain samples of RBC than of other tissues, it is a reasonable suggestion of Jeremy and his colleagues that measurement of lipid peroxidation in RBC may reflect changes in other tissues as well, and could be used as an index of peripheral tissue free radical load. However, more studies are needed to assess time course over which these changes occur, as well as the simultaneous measurement of lipid peroxidation in RBC compared with other tissues in an animal model. For example, membrane damage in one tissue may start at an earlier stage of diabetes than another tissue, depending on the htioxidants level or activities of antioxidative enzymes. There are more and more studies in support of hyperglycemiainduced oxygen radical generations and its role in the cellular
Metabolism, Vol40, No 4 (April), 1991: pp 442443
