Antioxidant SMe1EC2 modulates pentose phosphate pathway and glutathione-dependent enzyme activities in tissues of aged diabetic rats

Abstract

The pentose phosphate pathway and glutathione-associated metabolism are the main antioxidant cellular defense systems. This study investigated the effects of the powerful antioxidant SMe1EC2 (2-ethoxycarbonyl-8-methoxy-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b] indolinium dichloride) on pentose phosphate pathway (PPP) and glutathione-dependent enzyme activities in aged diabetic and aged matched control rats. Diabetes was induced by streptozotocin injection in rats aged 13–15 months. Diabetic and control rats were divided into two subgroups, one untreated and one treated with SMe1EC2 (10 mg/kg/day, orally) for 4 months. SMe1EC2 ameliorated body weight loss, but not hyperglycemia of aged diabetic rats. Diabetes resulted in decreased glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD) and glutathione-S-transferase (GST), yet in unchanged glutathione reductase (GR) in the liver of aged diabetic rats. In the liver of the aged control rats, SMe1EC2 did not affect G6PDH, 6PGDH and GR, but it inhibited GST. SMe1EC2 also failed to affect diabetes-induced decline in 6PGDH, it ameliorated G6PDH but produced further decline in GST in the liver of aged diabetic rats. In the kidney of aged rats, G6PDH and GST were found to be comparable among the groups, but diabetes up-regulated 6PGDH and GR; these alterations were prevented by SMe1EC2. In the heart of aged diabetic rats, while GST remained unchanged, the recorded increase in G6PD, 6PGD, GR was prevented by SMe1EC2. Furthermore, an unchanged GR and remarkable increases in G6PD, 6PGD and GST were found in the lung of the aged diabetic group. These alterations were completely prevented by SMe1EC2. The results suggest that in aged rats SMe1EC2 can ameliorate the response of the kidney, heart and lung but not that of the liver against diabetes-induced glucotoxicity by interfering with the activity of redox network enzymes.

The Redox Role of G6PD in Cell Growth, Cell Death, and Cancer

“…Altered G6PD status is implicated in many cellular pathophysiological processes and diseases, including hypoxia, inflammation, microbial infection, sepsis, pulmonary vessel dilation, diabetes, hypertension, kidney disease, and brain injuries [24,30,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126]. The PPP and glutathione-associated metabolic pathways are major antioxidant defense systems in cells.…”

“…Chronic inflammation in adipose tissue is implicated in insulin resistance found in obesity [117]. Downregulation of G6PD, 6-phosphogluconate dehydrogenase (6PGD) and glutathione-S-transferase (GST) is found in the liver of aged and streptozotocin-induced diabetic rats [106]. The antioxidant, SMe1EC2, increases the G6PD activity but not 6PGD and GST in diabetic rats.…”

People having hematological disorders and hypercoagulability state need extra precautions because of the increased risk of thrombosis after COVID-19 vaccination

“…People with hematological or hypercoagulability disorders such as G6PD deficiency, thalassemia, SCD, pyruvate dehydrogenase deficiency, thrombophilia, and sticky platelet syndrome have a higher risk of developing thrombosis, anemia, hemolysis, and embolism than healthy individuals. G6PD enzyme is the rate-limiting enzyme in the pentose phosphate pathway responsible for producing NADPH involved in maintaining the redox balance in the cell (22)(23)(24)(25). Therefore, G6PD enzyme deficiency causes enhanced oxidative stress directly associated with hemoglobin denaturation and intravascular hemolysis (23, [25][26][27].…”

Accelerated Kidney Aging in Diabetes Mellitus

“…The renal protection offered by Shenkang injection, a classic compound prescription, has also been demonstrated to retard high glucose-induced senescence of renal tubular cells [218]. Some extracts of herbs have exhibited antiaging properties, such as curcumin [219,220], a glycoprotein isolated from Fupenzi [221], tea polyphenols [222], the flavonoid 4,4 ′ -dimethoxychalcone (DMC) [102], and berberine [223]. These results imply that TCMs appear to have potential advantages to protect renal function against kidney aging in DM in the future.…”