Effect of Momordica grosvenori on oxidative stress pathways in renal mitochondria of normal and alloxan-induced diabetic mice. Involvement of heme oxygenase-1.

BACKGROUND: Oxidative stress plays an important role in the pathogenesis of diabetes and diabetic nephropathy. Momordica grosvenori (MG), a traditional medicinal herb used as substitute sugar for obese and diabetes, exhibits anti-oxidative activity in vitro. AIM OF THE STUDY: This study investigated the effect of MG on renal mitochondrial lipid peroxidation, anti-oxidative defense system, and a potent oxidative stress-responsive protein, heme oxygenase-1 (HO-1) of nondiabetic and alloxan-diabetic mice in different stages of diabetes.
METHODS: Male Balb/c mice were rendered diabetic by a single intra-peritoneal injection of alloxan (200 mg/kg), while control mice received sham saline injection. Control and diabetic mice were further subdivided according to their treatments: control (saline), low dose MG (150 mg/kg) and high dose MG (300 mg/kg), which were administered immediately after confirmation of hyperglycemia by gavage daily over an 8-week period. Mice were killed by cervical dislocation at 4th and 8th week, respectively, and serum and renal tissues were harvested. Serum glucose, lipid profile and renal function were evaluated; renal homogenate were subjected to determination of malondialdehyde (MDA) and glutathione (GSH) concentration, manganese superoxide dismutase (Mn-SOD), glutathione peroxidase (GSH-Px) and HO-1 activities, together with Mn-SOD and HO-1 mRNA expression; paraffin-embedded renal tissues was used for routine histopathological examination.
RESULTS: Short-term diabetes caused hyperglycemia and intensified oxidative stress in renal mitochondrial demonstrated by higher MDA and lower GSH levels than control group, accompanied by increased mRNA expression and activity of HO-1 and Mn-SOD, and augmented GSH-Px activity. Low dose of MG administration ameliorated hyperglycemia, inhibited HO-1 and Mn-SOD mRNA expression and reduced HO-1, Mn-SOD, GSH-Px activities. Diabetic mice did not demonstrate early symptoms of diabetic nephropathy until 8th week, characterized by hyperglycemia, hyperlipidemia, and renal damage. A progressive increment in MDA level and decrease in GSH level, as well as reduced mRNA expression and activity of Mn-SOD and HO-1 in the kidney were observed. Low dose of MG attenuated diabetic nephropa- thy symptoms partially, inhibited lipid peroxidation, up-regulated HO-1 and Mn-SOD mRNA expression, and increased HO-1 activity. Conclusions The study confirmed the involvement of oxidative stress in the development of diabetes mediated by the pro- and antioxidant role of HO-1, and pointed to the possible anti-oxidative mechanism of the anti-diabetic and nephroprotective action of MG.