The objective of the present study is to evaluate the effect of epigallocatechin gallate (EGCG) on aging-mediated cardiac hypertrophy, fibrosis, and apoptosis. The Wistar albino rats were divided into 4 groups (n = 18). Group I: young (3 months), group II: aged (24-26 months), group III: aged + EGCG (200 mg/kg for 30 days), and group IV: young + EGCG. At the end of 30 days, EGCG administration to the aged animals showed significant (P < 0.001) reduction of low-density lipoprotein, very low-density lipoprotein, triglyceride, total cholesterol with concomitant increase of high-density lipoprotein (P < 0.001) when compared with aged rats. Increased (P < 0.001) heart volume, weight with concomitant increase of left ventricular wall thickness, and reduced ventricular cavity were observed in aged rats supplemented with EGCG compared with aged animals. Histology and histomorphometry study of aged animals treated with EGCG showed marked increases in the diameter and volume of cardiomyocytes with concomitant reduction of numerical density when compared with aged animals. Reduced reactive oxygen species (P < 0.001) production with association of increased antioxidant defense system (P < 0.001) in aged hearts supplemented with EGCG when compared with aged animals. TUNEL staining and fibrosis showed a marked increase in apoptotic cell death (P < 0.001) and collagen deposition (P < 0.001) in aged animals treated with EGCG when compared with aged animals. Aged animals treated with EGCG showed a marked increase in protein expression of TGFβ, TNFα, and nuclear factor kappa B (NF-κB) and significant (P < 0.001) alteration in the gene expression of TGFβ, TNFα, NF-κB, α-SMA, and Nrf2 when compared with aged animals. Taken together, it is evident that EGCG may potentially inhibit aging-induced cardiac hypertrophy, fibrosis, and apoptosis, thereby preserving cardiac function. The proposed mechanism would be inhibition of reactive oxygen species-dependent activation of TGFβ1, TNFα, and NF-κB signaling pathway. Hence, the present study suggests that EGCG can be useful to fight against aging-induced cardiac hypertrophy, fibrosis, and apoptosis.

The objective of the current study is to analyze the effects of gestational diabetes on structural and functional changes in correlation with these two essential regulators of developing hearts in vivo using zebrafish embryos. We employed fertilized zebrafish embryos exposed to a hyperglycemic condition of 25 mM glucose for 96 h postfertilization. The embryos were subjected to various structural and functional analyses in a time-course manner. The data showed that exposure to high glucose significantly affected the embryo's size, heart length, heart rate, and looping of the heart compared to the control. Further, we observed an increased incidence of ventricular standstill and valvular regurgitation with a marked reduction of peripheral blood flow in the high glucose-exposed group compared to the control. In addition, the histological data showed that the high-glucose exposure markedly reduced the thickness of the wall and the number of cardiomyocytes in both atrium and ventricles. We also observed striking alterations in the pericardium like edema, increase in diameter with thinning of the wall compared to the control group.Interestingly, the expression of tbx5a and nppa was increased in the early development and found to be repressed in the later stage of development in the hyperglycemic group compared to the control. In conclusion, the developing heart is more susceptible to hyperglycemia in the womb, thereby showing various developmental defects possibly by altering the expression of crucial gene regulators such as tbx5a and nppa.

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The objective is to study the effects of high glucose on the morphological changes and to observe the expression of apoptosis regulatory proteins in the developing retina in-vivo using Zebrafish embryos. Wild type male and female zebrafish were allowed for normal mating and the fertilized eggs were collected and exposed to hyperglycemic conditions (25mMol D-Glucose) for 96 hours. The embryos were subjected to various morphological and histological analyses in a time dependent manner. The embryos showed morphological defects such as body curvature, abnormal eye shape and low pigmentation of the eye in the high glucose induced embryos compared to the control. Histomorphometry studies using H&E stained slides showed increased thickness of GCL and INL and thinning of the IPL in the retina of high glucose exposed embryos when compared to its time matched control. Furthermore, the TUNEL assay and modified trichrome staining indicated apoptosis of many cells in the high glucose induced group compared to the control. Immunohistochemistry (IHC) findings revealed that expression of Bax, Caspase3 & Caspase9 was increased with decreased expression of Bcl-2 in the high glucose treated group compared to control. From the present data it is concluded that gestational exposure to high glucose stimulate apoptotic cell in the developing retinal layers via activating the pro-apoptotic and repressing the anti-apoptotic proteins.