The College of Pharmacy discussed the PhD dissertation entitled “Effects of Dapagliflozin against Cyclophosphamide-induced Hepatotoxicity in Male Rats in Comparison to Silymarin” by the student Afrah Thiab Hlail and the supervisor, Professor Dr. Nada Naji AlShawi, at the Pharmacology and Toxicology Department.
The study aimed to investigate the protective effects of dapagliflozin against cyclophosphamide-induced hepatotoxicity and to compare these effects with the efficacy of silymarin.
The study included fifty male rats randomly divided into five groups of 10 and treated as follows: Group I rats received normal saline orally for ten consecutive days; Group II rats received sodium-carboxymethylcellulose orally for ten consecutive days; Group III rats received daily intraperitoneal (IP) injection of cyclophosphamide at a dose of 30 mg/kg for ten consecutive days; Group IV rats received dapagliflozin at a dose of 3 mg/kg orally and daily IP injection of cyclophosphamide at a dose of 30 mg/kg for ten consecutive days; Group V rats received silymarin at a dose of 200 mg/kg orally and daily IP injection of cyclophosphamide at a dose of 30 mg/kg for ten consecutive days. On day eleven, the rats were sacrificed, and blood and liver tissue samples were collected for biochemical, gene expression, and histological analysis.
The results showed that treatment with dapagliflozin or silymarin resulted in a significant improvement in the histological changes induced by cyclophosphamide in liver tissue, in addition to a reduction in the levels of the enzymes ALT and AST compared with the cyclophosphamide group of rats. Furthermore, pretreatment with dapagliflozin or silymarin reduced cyclophosphamide-induced oxidative stress by increasing GSH and SOD levels and Nrf2 gene expression, while decreasing MDA levels in liver tissues. Moreover, pretreatment with dapagliflozin or silymarin alleviated cyclophosphamide-induced inflammation and apoptosis by downregulating the gene expression of TNF-α and IL-1β and reducing caspase-3 levels, along with increasing the gene expression of HO-1 and IL-10 and the levels of Bcl2, HNF4α, and HNF6 in liver tissues.
The study recommended conducting further research involving the use of different doses of dapagliflozin and silymarin for longer periods to evaluate the protective efficacy of these drugs against hepatotoxicity and to investigate their molecular mechanisms in greater depth.
