**Author details**

lesterol-fed rabbits, LDL oxidation and ox-LDL-mediated macrophage apoptosis (Chen et al., 2003; Chang et al., 2006). Wang et al. (2009) demonstrated that aqueous extract of *Hibis‐ cus sabdariffa* L. (HSE) is capable of increasing catalase and glutathione activities significantly in diabetic kidney. In histological examination, HSE improves hydropic change of renal proximal convoluted tubules in diabetic rats. HSE was also revealed to up-regulate Akt/Bad/ 14-3-3 and NF-κB-mediated transcription in diabetic nephropathy. Luteolin is a plant-de‐ rived flavonoid, it has various biological activities including anti-inflammatory (Jang et al., 2008), antimutagenic, and antitumorigenic properties (Ross and Kasum, 2002). It also pos‐ sesses direct antioxidant activity (L´opez-L´azaro, 2009), and may be useful in treatment of many chronic disease associated with oxidative stress, such as cardiovascular diseases (McCord, 1985; Jeroudi et al., 1994), liver diseases (Comporti, 1985; Poli et al., 1987), diabetes (Oberley, 1988), and aging (Harman, 1981). Wang et al. (2011) demonstrated that luteolin has protecting effect against development of diabetic nephropathy by changing the superox‐ ide dismutase (SOD) activity, the malondialdehyde (MDA) content, and expression of Heme

On the other hand, some evidences show the exogenous or endogenous antioxidants also can reduce diabetic nephropathy. Oxidative stress via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and vascular endothelial growth factor (VEGF) pathway are documented to play important roles in the development of diabetic nephropathy. Nam et al. (2009) showed the effects of apocynin, a NADPH oxidase inhibitor, on diabetic nephrop‐ athy. They found that apocynincan not significantly decrease serum glucose levels but re‐ duce urinary protein and albumin excretions. It is improved in glomerular and mesangial expansion as the apocynin treatment. Apocynin also decreased glomerular VEGF expression and reduced the concentration of 24 h urinary 8-OHdG and MDA. Additionally, Lee et al. (2005) demonstrated that antioxidant taurine prevented glomerular hypertrophy, mesangial expansion, and proteinuria in diabetic rats. Overexpression of catalytic antioxidants was al‐ so shown to protect against diabetic injury in several transgenic animals. Craven et al. (2001) showed that diabetic mice transgenic for Cu/Zn SOD had significantly lower urinary albu‐ min excretion, glomerular hypertrophy, and glomerular expression of TGF-β1 and collagen IV protein compared to non-transgenic mice. Hamada et al. (2007) demonstrated that over‐ expression a small antioxidant, thioredoxin 1, effectively inhibited 8-OHdG in the kidney, albuminuria, mesangial expansion, and tubular injury in diabetic mice. Du et al. (2003) found that overexpression of MnSOD in bovine aortic endothelial cells prevented high glu‐ cose-induced activation of PKC, NK-kB, hexosamine, and advanced glycation end product (AGE) pathways. Brezniceanu et al. (2007) demonstrated that renal catalase overexpression in db/db mice attenuated ROS generation, angiotensinogen, proapoptotic gene expression

Although strict glycemic control is very important in DM patients, many of the current standard therapeutic approaches may also ameliorate oxidative stress as pleiotropic effects (Singh et al., 2011), such as angiotensin-2 converting enzyme (ACE) inhibitors(Kobayashi et al., 2006), angiotensin-2 receptor blockers (ARB) (Ogawa et al., 2006) and aldosterone block‐ ers (spironolactone) (Takebayashi et al., 2006). They activate eNOS to increase bioavailability

Oxygenase-1 (HO-1) protein.

392 Type 1 Diabetes

and apoptosis in the kidneys of diabetic mice *in vivo*.

Wen-Chin Lee1,2\*, Chau-Jong Wang3 and Huei-Jane Lee3

1 Division of Nephrology, Department of Internal Medicine, Show Chwan Memorial Hospi‐ tal, Changhua, Taiwan

2 General Education Center, Central Taiwan University of Science and Technology, Tai‐ chung, Taiwan

3 Institute of Biochemistry and Biotechnology, Medical College, Chung Shan Medical Uni‐ versity, Taichung, Taiwan
