Hepatotoxic Potential of Gibberellic Acid (GA(3)) in Adult Male Albino Rats

Gibberellic acid (GA(3)), a plant growth regulator, is widely used in agriculture of many countries including Egypt. However, its potential hazardous effects on human health were relatively unexplored. The purpose of this study was to investigate the effects of sub-chronic toxicity of GA(3) on hepatic function and structure in adult male albino rats and also to determine the effects of withdrawal of GA(3) on the affected parameters following 6 weeks of follow up. Forty adult male albino rats were equally divided into four groups; the first group was used as a negative control, while the second group (positive control group) received NaOH; the vehicle. Animals of the third group (GA3 group) received 75 ppm of GA3 daily in drinking water for six weeks. Animals of the last group (Recovery group) received the same treatment as the third group for six weeks then were left without any treatment for another 6 weeks. At the end of the experimental period, all rats were sacrificed for assessment of liver function tests; ALT, AST, GGT and ALP. Liver specimens were collected for histopathological examination and assessment of hepatic levels of SOD, CAT, GSHPx and MDA. The results revealed that GA(3) sub-chronic toxicity induced a significant increase in AST, ALT, GGT and ALP as compared to control group. There was also a significant increase in hepatic malondialdehyde level with a significant decrease in SOD, CAT, and GSHPx enzymes activity in comparison with control groups. Histopathological examination using light microscope showed; hepatocyte vacuolization and inflammatory cellular infiltration. Most of hepatocytes appeared shrunken with pyknotic nuclei. Moreover, Bcl-2 immunolocalization revealed over-expression of this protein in both hepatocytes and endothelial cells of hepatic sinusoids. Electron microscopic examination revealed most of hepatocytes were with shrinkage nuclei with condensation of its heterochromatin and cytoplasmic vacuolization. On the other hand, stoppage of GA3 administration for 6 weeks has resulted in some sort of regression of the previously mentioned hepatoxic effects. In conclusion: results of the current study suggested gibberellic acid was a potent pro-oxidant that induced a significant hepatotoxicity in adult male albino rats, while 6 weeks period of follow up was insufficient for complete recovery of these toxic effects.