BACKGROUND: alpha-Lipoic acid is a potent antioxidant that improves renal function in diabetes by lowering glycemia, however, the mechanisms by which alpha-lipoic acid exerts its antioxidant effects are not completely understood. METHODS: Metabolic parameters, renal function, and morphology, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and subunit expression were analyzed in nondiabetic and streptozotocin-induced diabetic rats fed normal rat chow (control) with or without alpha-lipoic acid (30 mg/kg body weight) for 12 weeks. RESULTS: Blood glucose was increased with diabetes (nondiabetic + control 89 +/- 3 mg/dL and diabetic + control 336 +/- 28 mg/dL) and was similar with alpha-lipoic acid treatment (diabetic +alpha-lipoic acid 351 +/- 14 mg/dL). In contrast, alpha-lipoic acid attenuated albuminuria (nondiabetic + control 8.9 +/- 1.3 mg/day; diabetic + control 28.1 +/- 4.6 mg/day; and diabetic +alpha-lipoic acid 17.8 +/- 1.2 mg/day) associated with diabetes. Similarly, alpha-lipoic acid attenuated glomerulosclerosis (nondiabetic + control 0.22 +/- 0.01; diabetic + control 0.55 +/- 0.04; diabetic +alpha-lipoic acid 0.36 +/- 0.03), tubulointerstitial fibrosis (nondiabetic + control 0.42 +/- 0.18; diabetic + control 1.52 +/- 0.05; diabetic +alpha-lipoic acid 1.10 +/- 0.05), superoxide anion (O(.-) (2)) generation (nondiabetic +control 15.8 +/- 1.7; diabetic +control 87.1 +/- 3.5; diabetic +alpha-lipoic acid 25.5 +/- 3.3 RLU/mg protein), and urine 8-isoprostane (8-iso) excretion (nondiabetic + control 7.4 +/- 1.4; diabetic + control 26.0 +/- 4.5; diabetic +alpha-lipoic acid 19.6 +/- 5.6 ng/day) associated with diabetes. alpha-Lipoic acid also reduced kidney expression of NADPH oxidase subunits p22phox and p47phox. Surprisingly, alpha-lipoic acid appears to cause pro-oxidant effects in nondiabetic animals, resulting in increased albuminuria (nondiabetic +alpha-lipoic acid 14.2 +/- 1.2 mg/day), increase in plasma creatinine levels (nondiabetic + control 59 +/- 6; diabetic + control 68 +/- 6; nondiabetic +alpha-lipoic acid 86 +/- 9; diabetic +alpha-lipoic acid 69 +/- 7 mumol/L), exacerbated glomerulosclerosis and tubulointerstitial fibrosis, increased O(.-) (2) generation, up-regulated p22phox and p47phox expression and increased 8-iso excretion. CONCLUSION: We conclude that alpha-lipoic acid improves albuminuria and pathology in diabetes by reducing oxidative stress, while in healthy animals, alpha-lipoic acid may act as a pro-oxidant, contributing to renal dysfunction.
BACKGROUND:alpha-Lipoic acid is a potent antioxidant that improves renal function in diabetes by lowering glycemia, however, the mechanisms by which alpha-lipoic acid exerts its antioxidant effects are not completely understood. METHODS: Metabolic parameters, renal function, and morphology, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and subunit expression were analyzed in nondiabetic and streptozotocin-induced diabeticrats fed normal rat chow (control) with or without alpha-lipoic acid (30 mg/kg body weight) for 12 weeks. RESULTS:Blood glucose was increased with diabetes (nondiabetic + control 89 +/- 3 mg/dL and diabetic + control 336 +/- 28 mg/dL) and was similar with alpha-lipoic acid treatment (diabetic +alpha-lipoic acid 351 +/- 14 mg/dL). In contrast, alpha-lipoic acid attenuated albuminuria (nondiabetic + control 8.9 +/- 1.3 mg/day; diabetic + control 28.1 +/- 4.6 mg/day; and diabetic +alpha-lipoic acid 17.8 +/- 1.2 mg/day) associated with diabetes. Similarly, alpha-lipoic acid attenuated glomerulosclerosis (nondiabetic + control 0.22 +/- 0.01; diabetic + control 0.55 +/- 0.04; diabetic +alpha-lipoic acid 0.36 +/- 0.03), tubulointerstitial fibrosis (nondiabetic + control 0.42 +/- 0.18; diabetic + control 1.52 +/- 0.05; diabetic +alpha-lipoic acid 1.10 +/- 0.05), superoxide anion (O(.-) (2)) generation (nondiabetic +control 15.8 +/- 1.7; diabetic +control 87.1 +/- 3.5; diabetic +alpha-lipoic acid 25.5 +/- 3.3 RLU/mg protein), and urine 8-isoprostane (8-iso) excretion (nondiabetic + control 7.4 +/- 1.4; diabetic + control 26.0 +/- 4.5; diabetic +alpha-lipoic acid 19.6 +/- 5.6 ng/day) associated with diabetes. alpha-Lipoic acid also reduced kidney expression of NADPH oxidase subunits p22phox and p47phox. Surprisingly, alpha-lipoic acid appears to cause pro-oxidant effects in nondiabetic animals, resulting in increased albuminuria (nondiabetic +alpha-lipoic acid 14.2 +/- 1.2 mg/day), increase in plasma creatinine levels (nondiabetic + control 59 +/- 6; diabetic + control 68 +/- 6; nondiabetic +alpha-lipoic acid 86 +/- 9; diabetic +alpha-lipoic acid 69 +/- 7 mumol/L), exacerbated glomerulosclerosis and tubulointerstitial fibrosis, increased O(.-) (2) generation, up-regulated p22phox and p47phox expression and increased 8-iso excretion. CONCLUSION: We conclude that alpha-lipoic acid improves albuminuria and pathology in diabetes by reducing oxidative stress, while in healthy animals, alpha-lipoic acid may act as a pro-oxidant, contributing to renal dysfunction.
Authors: Nouf M Al-Rasheed; Nawal M Al-Rasheed; Hala A Attia; Iman H Hasan; Maha Al-Amin; Hanaa Al-Ajmi; Raeesa A Mohamad Journal: J Physiol Biochem Date: 2013-04-18 Impact factor: 4.158
Authors: Gehad A El-Nakib; Tarek M Mostafa; Tarek M Abbas; Mamdouh M El-Shishtawy; Mokhtar M Mabrouk; Mohammed A Sobh Journal: Int J Nephrol Renovasc Dis Date: 2013-08-27
Authors: Varatharajan Rajavel; Munavvar Zubaid Abdul Sattar; Mahmood Ameen Abdulla; Normadiah M Kassim; Nor Azizan Abdullah Journal: Evid Based Complement Alternat Med Date: 2012-11-22 Impact factor: 2.629