Methotrexate (MTX) is a drug used in the treatment of various types of cancer and inflammatory diseases, but its clinical use has been restricted due to its toxicity. Apigenin (API) is an effective flavonoid with antioxidant and anti-inflammatory properties. The aim of this study was to determine the protective effect of API against MTX-induced liver and kidney toxicity. Four groups with 12 male mice each were used. The control and API groups were received 0.9% saline (ip) and API (3 mg/kg ip) for 4 days, respectively. The MTX group were given a single dose of MTX (20 mg/kg ip) on the fourth day. The MTX + API group were administered API for 7 days and then MTX on fourth day. Blood, liver and kidney were collected to evaluate tissue injury markers, oxidative stress biomarkers, and histopathological and immunohistochemical assessments. In MTX-treated group, significant increases in aminotransferases activities, creatinine and malondialdehyde (MDA) levels and significant decreases in catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase1 (SOD1) activities and glutathione (GSH) levels were determined compared to the control group. Furthermore, histopathological changes and significant increases in caspase-3, C-reactive protein (CRP), granulocyte colony-stimulating factor (G-CSF), and inducible nitric oxide synthase (iNOS) expressions were detected in both liver and kidney tissues of MTX-treated mice. Pretreatment with API alleviates liver and kidney toxicity by attenuating oxidative stress and tissue injury markers, histopathological alterations, and apoptosis and inflammation. These results suggest that API has a protective effect against oxidative stress and liver-kidney toxicity induced by MTX.

This research aimed to investigate the protective effect of p-CA, a derivative of phenolic acid, against toluene-induced oxidative damage. A total of 32 Sprague-Dawley male rats, 8 in each group, were used. A total of 4 groups were formed as control, toluene, p-CA and toluene+p-CA. Animals in the control group, toluene group and p-CA group were given 0.9 % NaCl, 0.9 mg kg-1 b.w toluene and 100 mg kg -1 b.w p-CA orally for 21 days, respectively. The animals in toluene+p-CA group were received p-CA for 3 days and from day 4, toluene and p-CA were applied together daily until day 25. On the 25th day, the study was terminated, and blood samples were collected. Catalase (CAT) and glutathione peroxidase (GSH-Px) activities and malondialdehyde (MDA) and glutathione (GSH) levels in the erythrocytes and superoxide dismutase (SOD) activity in plasma samples were determined. In this study, CAT and SOD activities and MDA level significantly (p <0.05) increased, GSH level and GSH-Px activity significantly (p <0.05) decreased in the blood samples of toluene group compared to the control group. In toluene+p-CA group, significant (p <0.05) increases in GSH level and GSH-Px activity and significant (p <0.05) decreases in MDA level and SOD and CAT activities were detected compared to the toluene group. It has been determined that toluene caused oxidative stress and lipid peroxidation in blood tissue and against this oxidative damage, p-CA had a protective effect.

Objective. The aim of this study was to determine the protective effect of p-coumaric acid (p-CA) against toluene-induced hepatotoxicity, nephrotoxicity and neurotoxicity in rats. Materials and methods. A total of 32 Sprague-Dawley male rats, 8 in each group, were used. 4 groups were formed as control, toluene, p-CA and toluene+p-CA. Animals in the control group, toluene group and p-CA group were given 0.9% NaCl, 0.9 mg/kg b.w toluene and 100 mg/kg b.w p-CA orally for 21 days, respectively. The animals in toluene+p-CA group were received p-CA for 3 days and from day 4, toluene and p-CA were applied together daily until day 25. On the 25th day, the study was terminated, blood and tissue samples were collected. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatinine levels in serum, glutathione peroxidase (GSH-Px) activity and malondialdehyde (MDA) and glutathione (GSH) levels in the tissue samples were determined. Results. In this study, it was determined that there were significant increases in ALT and AST activities, and creatinine levels in toluene-induced group compared to control group. Moreover, there was a decrease in the GSH-Px activities and GSH levels, and an increase in the MDA levels compared to the control group. However, in the toluene+p-CA group, significant decreases in aminotransferases activities, creatinine and MDA levels, and significant increases in GSH-Px activities and GSH levels were determined compared to the toluene group. Conclusions. It has been determined that p-CA has a protective effect against toluene-induced hepatotoxicity, nephrotoxicity and neurotoxicity.