Nephro-toxic effects of intraperitoneally injected EGCG in diabetic mice: involvement of oxidative stress, inflammation and apoptosis

Abstract

Epigallocatechin gallate (EGCG) has been studied for its beneficial effects. However, some case reports have associated EGCG supplementation with hepato-toxicity. In the present study, we investigated the possible nephro-toxic effects of EGCG in diabetic mice. Streptozotocin (150 mg/kg, i.p.) was injected in mice for diabetes induction. EGCG (100 mg/kg/day, i.p.) was then given for 4 days. The administration of EGCG to diabetic mice caused 60% mortality with no death recorded in other groups. Blood samples were collected for estimation of serum cystatin C, neutrophil gelatinase-associated lipocalin and blood urea nitrogen. Animals were then sacrificed and kidneys were rapidly excised for estimation of oxidative stress markers (NADPH oxidase, reduced glutathione, total antioxidant capacity, nuclear factor erythroid 2-related factor 2, heat shock protein 90, hemeoxygenase-1), as well as inflammatory markers (nuclear factor kappa-B and tumor necrosis factor-α). Administration of EGCG to diabetic mice showed significant elevation in serum cystatin C and neutrophil gelatinase-associated lipocalin, marked increase in oxidative stress and inflammatory states in addition to marked over expression of active caspase-3. Histopathological examination confirmed EGCG induced renal damage in diabetic mice. In conclusion, despite of its well known favorable effects, EGCG could paradoxically exhibit nephro-toxic effect in the presence of diabetes.

Epigallocatechin-3-Gallate Ameliorates Angiotensin II-Induced Oxidative Stress and Apoptosis in Human Umbilical Vein Endothelial Cells through the Activation of Nrf2/Caspase-3 Signaling

“…EGCG enhances cancer cell apoptosis [20,21]. It is also used for the prevention of cardiovascular diseases, especially atherosclerosis and coronary heart disease [17,22]. However, little is known about how EGCG ameliorates Ang II-induced oxidative stress and mitochondrial dysfunction in human endothelial cells.…”

“…(−)-Epigallocatechin-3-gallate (EGCG), the major compound of green tea, has anti-inflammatory, antioxidative, and antiangiogenic effects both in vitro and in vivo [17,18,19]. EGCG enhances cancer cell apoptosis [20,21].…”

Induction of Endoplasmic Reticulum Stress Pathway by Green Tea Epigallocatechin-3-Gallate (EGCG) in Colorectal Cancer Cells: Activation of PERK/p-eIF2α/ATF4 and IRE1α

“…is study revealed that EGCG has the potential to induce robust Caspase 3/7 activity. Recently, the Caspase 3 activity induced by EGCG treatments was also observed in bladder cancer cells SW780 [45] and chondrosarcoma cells [46], as well as in diabetic mice [47], indicating that EGCG plays a role in apoptosis via Caspase 3 activity. In general, polyphenols such as EGCG induced apoptosis in a caspasedependent manner [48][49][50].…”

Long-term apoptosis-related protein expression in the diabetic mouse ovary

“…Several studies have shown an association between DM and female reproductive disturbances, including amenorrhea, early menopause onset and infertility [ 2 , 6 , 9 , 10 , 12 – 18 ]. These alterations have been related to the injurious effects of hyperglycemia through the overproduction of AGEs and ROS, which trigger the caspase 3 apoptosis pathway [ 2 , 4 , 6 , 13 , 16 ]. However, these studies analyzed the effects of DM at a single time point, without correlating follicular loss with the expression of apoptotic proteins.…”

“…Diabetes mellitus (DM) is a chronic metabolic disorder affecting more than 6% of the global population [ 1 ]. Chronically high glucose levels have deleterious effects on the structure and function of various organs [ 2 – 4 ]. Tissue damage has been related to the increased formation of advanced glycation end products (AGEs) [ 5 , 6 ] and the overproduction of reactive oxygen species (ROS) [ 2 , 5 ], which can cause oxidative stress, vascular endothelial cell damage and inflammatory cytokine production [ 3 , 7 , 8 ].…”