Ameliorative Effects of Nettle (Urtica dioica) Seed Extract on Methotrexate-Induced Hepatorenal Damage in Rats

In this study, it was aimed to examine the potential therapeutic effects of Urtica dioica seed (UDS) oil on hepatorenal damage induced by methotrexate in rats. Thirty-two Wistar albino rats were divided into four groups: Control, Methotrexate (MTX, 20 mg/kg i.p.), UDS (30 ml/kg feed containing UDS), and MTX+UDS (20 mg/kg i.p. + 30 ml/kg feed containing UDS oil, respectively). At the end of the six-week study, the MTX-treated group demonstrated elevated levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) in serum and increased levels of malondialdehyde (MDA), an indicator of lipid peroxidation in liver, kidney, and blood tissues. However, reduced glutathione (GSH) levels (apart from erythrocytes) showed a significant decrease (p<0.005). The MTX group's liver and erythrocyte tissues showed a significant decrease in glutathione reductase (GR) activity compared to the control. Additionally, there was a significant decrease in the activities of glutathione peroxidase (GPx) and catalase (CAT) in the MTX group as compared to the control. The co-administration of MTX+UDS decreased liver MDA concentration and the levels of the enzymes AST, ALT, and LDH compared to the MTX group. On the other hand, there was an increase in kidney glutathione S-transferase (GST) activity and GSH levels. Histopathological investigation revealed that pellets containing UDS oil significantly reduced the degenerative and necrotic changes that MTX had generated in the liver and kidney, including parenchymal and hydropic degeneration and inflammatory cell infiltration. Immunohistochemical staining showed that caspase 3, a marker of apoptosis, decreased significantly with the administration of UDS oil. In conclusion, MTX-induced hepatorenal damage was either prevented or greatly decreased by UDS oil.