Grape seeds proanthocyanidin extract as a hepatic-reno-protective agent against gibberellic acid induced oxidative stress and cellular alterations

Abstract

The present study aims to investigate the heptonephro-protective effect of grape seeds proanthocyanidin extract (GSPE) against the risks induced by gibberellic acid (GA3) in male rats. The results recorded that GA3 caused a significant increase in total lipids, total cholesterol, triglycerides and LDL-C levels in serum, concomitant with a significant decrease in serum HDL-C. A significant increase in serum AST, ALT, urea and creatinine, while, a significant decrease in total protein content in serum was observed in rats given GA3. Hepatic and renal lipid peroxidation product (MDA) was significantly increased, meanwhile, total antioxidant capacity (TAC), glutathione, and catalase levels were significantly decreased. In addition, there was a negative change in liver structure including dilatation in the central veins with degeneration of endothelium cells and cellular injury around the veins as well as in the kidney structure such as lesion in both glomeruli and tubules, detachment of the Malpighian corpuscles from the Bowman's capsule's epithelium, shrinkage in the glomerular capillary network. However, almost all of these adverse effects seemed to be ameliorated by oral administration of GSPE with GA3 to rats for 2 month indicating the protective effect of grape seeds GSPE on GA3 induced oxidative stress in rats.

Fig. 1

a Photomicrograph of a transverse section of the liver of the control rat group showing normal structure for hepatic cells (h), sinusoidal spaces (s) with Kupffer cells (k) and central vein (CV). (X200), b Photomicrograph of a transverse section of the liver of the GSPE rat group showing normal structure of the liver as for the control. (X200), c Photomicrograph of a transverse section of the liver after treatment with GA₃, showing dilated central vein (CV) and degeneration of endothelium cells. Note vesicuolation of the nuclei (arrow) and fat vacuoles (head arrows). (X250), d Photomicrograph of a transverse section of the liver after treatment with GA₃, showing: vacuolation (v) of the cytoplasm of hepatocytes, and sinusoid filled with red blood cells (*). (X400), e Photomicrograph of a transverse section of the liver after treatment with GA₃, showing dilated central vein (CV) with severe lymphocytic infiltration. (X400), f Photomicrograph of a transverse section of the liver after treatment with GA₃, illustrating the portal region. Note severe lymphocytic infiltration. (X250), g Photomicrograph of a transverse section of the liver after treatment with GSPE + GA₃ showing appearance of improvement of the central vein (CV) structure. (X250), h Photomicrograph of a transverse section of the liver after treatment with GSPE + GA₃ showing improvement of the structure of the portal region. (X250)

Fig. 2

a Photomicrograph of a transverse section of the kidney of control group, showing the normal structure, Bowman’s capsules (arrow), glomerulus (G), convoluted tubules (t). (X250), b Photomicrograph of a transverse section of the kidney of GSPE rat group, showing the normal structure of the kidney as control. (X250), c Photomicrograph of a transverse section of the kidney after treatment with GA₃, showing detachment of two Malpighian corpuscles. Note vacuolated glomeruli (arrow). (X 250), d Photomicrograph of a transverse section of the kidney after treatment with GA₃, showing the shrinkage of the glomerular capillaries leaving space between them and the wall (*). Note the degeneration of the cellular epithelium of the tubules vacuoles (v), fat vacuoles (F). (X400), e Photomicrograph of a transverse section of the kidney after treatment with GA₃, showing the dilatation of the renal tubules. Note hemorrhage (arrow) and lymphocytic infiltration (head arrows). (X400), f Photomicrograph of a transverse section of the kidney after treatment with GSPE + GA₃. Note the appearance of improvement of the kidney structure. (X250)