Abstract
The plant growth regulator gibberellic acid (GA3) is widely used in agriculture in many countries. However, little is known about its danger to human health or its physiologic and biochemical pathways. Our study examined the effect of GA3 on liver and kidney function and the effect of quercetin on the hepatorenal toxicity induced by GA3 in four groups of male albino rats. For 4 weeks, the control group (CNT) received saline, the quercetin group (QR) received daily intraperitoneal injections of quercetin (50 mg/kg/BW) dissolved in saline, the gibberellic acid group (GA3) received GA3 (55 mg/kg/BW) via oral gavage, and the protective group (QR) was injected with quercetin and gavaged with GA3 in the same doses used in the QR and GA3 groups (50 mg/kg/BW +GA3 and 55 mg/kg/BW). GA3 induced liver and kidney injury, as shown by elevated serum glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, and gamma-glutamyl transferase (GPT, GOT, and GGT) as well as increased levels of creatinine, urea, and uric acid. Hepatorenal toxicity was demonstrated by a significant increase in levels of serum and tissue malondialdehyde (MDA) and decreased antioxidant enzyme activity, such as catalase (CAT) and superoxide dismutase (SOD), accompanied by a subsequent decrease in glutathione peroxidase (GPx) levels in liver and kidney tissue of GA3-treated rats. Administration of quercetin (QR) significantly protected hepatorenal tissue against the toxic effect of GA3 through normalization of the hepatic and renal function markers. It also retrieved the antioxidant ability by modulating the hepatorenal toxic effect at the molecular level through upregulation of antiapoptotic genes and downregulation of transforming growth factor-β1 (TFG-β1), cyclooxygenase-2 (COX-2), and nuclear factor-kappa B (NF-κB). Impairment of liver and kidney function was confirmed by histologic and immunohistochemical analyses. Pretreatment with quercetin was effective at attenuating histopathologic changes in hepatic and renal tissues by regulating the immunoexpression of caspase-3 and Bcl-2 to return them to more normal values. PRACTICAL APPLICATIONS: The confirmed hepatorenal dysfunction caused by GA3 was ameliorated by quercetin administration. Moreover, quercetin demonstrated the potential to reverse hepatorenal dysfunction by regulating inflammatory and antioxidant properties, inhibiting the production of free radicals and inflammation-associated cytokines, and modulating antioxidants and antiapoptotic activity.