What question did this study set out to answer?

To evaluate the potential myocardial toxicity and underlying mechanisms of an epigallocatechin gallate (EGCG) preparation in streptozotocin-induced diabetic mice.

May 14, 2018Scientific ReportsOpen Access

Paradoxical cardiotoxicity of intraperitoneally-injected epigallocatechin gallate preparation in diabetic mice

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Why the study?

Does EGCG preparation induce myocardial toxicity in diabetic mice?

Key Points

To evaluate the potential myocardial toxicity and underlying mechanisms of an epigallocatechin gallate (EGCG) preparation in streptozotocin-induced diabetic mice.
Induced diabetes in mice via intraperitoneal administration of streptozotocin (150 mg/kg, IP).
Administered an EGCG preparation (100 mg/kg/day, IP) for 4 consecutive days to diabetic mice.
Assessed cardiac damage using electrocardiography, serum cardiac biomarkers (troponin-I and CK-MB), histopathology, and molecular assays for oxidative stress, inflammation, and apoptosis.
EGCG administration produced electrocardiographic abnormalities, microscopic myocardial injury, and elevated serum creatine kinase-MB and troponin-I levels in diabetic mice.
Myocardial oxidative stress increased following EGCG treatment, marked by elevated NADPH oxidase, lipid peroxides, and nitrotyrosine, alongside depleted Nrf2, HO-1, and glutathione reserves.
EGCG provoked cardiac inflammatory and apoptotic responses, upregulating NF-κB, TNF-α, inducible nitric oxide synthase, and active caspase-3.

Structured PICO

Does EGCG preparation induce myocardial toxicity in diabetic mice?

Population

Diabetic mice (induced by streptozotocin 150 mg/kg, IP)

Intervention

Epigallocatechin gallate (EGCG) preparation (100 mg/kg/day, IP for 4 days)

Outcome

Myocardial toxicity (electrocardiographic changes, serum creatine kinase-MB, troponin-I levels, and microscopic myocardial damage)safety

Intraperitoneal administration of EGCG preparation exacerbates diabetes-induced cardiotoxicity in mice, highlighting potential safety concerns for its use in diabetic conditions.

Implication

May warrant caution with EGCG in diabetes; hypothesis-generating for cardiotoxicity and requires human studies.

Abstract

Numerous clinical and bioavailability studies addressed epigallocatechin gallate (EGCG) beneficial effects; however, our previous work revealed EGCG-induced nephrotoxicity in the presence of diabetes. In this study, the potential myocardial toxicity of EGCG preparation (100 mg/kg/day, IP; 4 days) in diabetic mice injected with streptozotocin (STZ; 150 mg/kg, IP) was investigated. Diabetic mice receiving EGCG preparation showed electrocardiographic changes in addition to elevation of both serum creatine kinase-MB and troponin-I levels accompanied by microscopic myocardial damage. Additionally, myocardial NADPH oxidase, lipid peroxides and nitrotyrosine were increased in the vicinity of decreases of nuclear factor erythroid 2-related factor 2, hemeoxygenase-1, reduced glutathione, total antioxidant capacity, glutathione peroxidase and reductase and heat shock protein 90. Moreover, in diabetic mice, EGCG preparation increased myocardial nuclear factor-kappa B and tumor necrosis factor-alpha in addition to pronounced overexpression of inducible nitric oxide synthase and active caspase-3. Therefore, this study substantiates that EGCG-mediated deterioration compromises diabetes-induced cardiotoxicity to solidify our previous report for its potential nephrotoxicity in the same experimental setting.